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Calcium phosphate nanoparticles (60 nm) were stabilized with either polyethyleneimine (PEI; polycationic electrolyte) or carboxymethylcellulose (CMC; polyanionic electrolyte). Next, a silica shell was added and terminated with either azide or alkyne groups via siloxane coupling chemistry. The particles were covalently functionalized by copper-catalyzed azide-alkyne cycloaddition (CuAAC; click chemistry) with proteins or gold nanoparticles that carried the complementary group, i.e., either alkyne or azide. The model proteins hemoglobin and bovine serum albumin (BSA) were attached as well as ultrasmall gold nanoparticles (2 nm). The number of protein molecules and gold nanoparticles attached to each calcium phosphate nanoparticle was quantitatively determined by extensive fluorescent labelling and UV–Vis spectroscopy on positively (PEI) or negatively (CMC) charged calcium phosphate nanoparticles, respectively. Depending on the cargo and the nanoparticle charge, this number was in the range of several hundreds to thousands. The functionalized calcium phosphate particles were well dispersible in water as shown by dynamic light scattering and internally amorphous as shown by X-ray powder diffraction. They were easily taken up by HeLa cells and not cytotoxic. This demonstrates that the covalent surface functionalization of calcium phosphate nanoparticles is a versatile method to create transporters with firmly attached cargo molecules into cells.

Neural stem cells (NSCs) present attractive natural drug delivery systems (DDSs). Their migratory potential enables crossing of the blood-brain barrier and efficient and selective accumulation near malignant cells. Here, we present the potential of NSCs as DDSs for nucleoside analogue conjugated nanogels (NGs). Two different approaches were investigated: the intracellular loading and extracellular cell surface decoration with NGs. For both designs, the tumor-specific migratory potentials of NSCs remained unchanged; however, the intracellular loading showed a shorter NG retention. The cell surface decoration protocol yielded a high loading capacity of 100% after 1 h and a prolonged drug retention. A redox-sensitive linker between NGs and the nucleoside analogue 5-ethynyl-2 '-deoxycytidine (EdC) allowed a tumor environment-specific drug release and its efficient and preferential incorporation into the DNA of the tumor cells. Interestingly, the tumor-trafficking potentials of NSCs were significantly potentiated by irradiation of tumor cells. In conclusion, this study indicates the potentials of cell surface-decorated NSCs as DDSs for tumor specific release, cellular uptake, and incorporation of EdC into DNA.

DNA may be the most versatile molecule discovered to date. Beyond its well-known central role in genetics, DNA has the potential to be a remarkably usefultechnological material. It has been demonstrated as a scaffold for the assemblyof organic and inorganic nanomaterials [1]; a vehicle for drug delivery [2]; amedium for computation [3]; and a possible wire for transporting electricalsignals [4]. A key factor in exploiting DNA in these ways is the ability tointegrate DNA with other materials. In this paper, we review two approachesto forming DNA complexes with functional nanomaterials: (1) linking DNAwith single-wall carbon nanotubes (SWCNTs), which can then be used asnanoscale electrical contacts for probing electron transport in DNA; and (2)directed nanoassembly of Au nanoparticles using DNA/PNA (peptide nucleicacid) hybrid scaffolds.

Combined therapy with penicillins and aminoglycosides has been proved beneficial to address many persistent bacterial infections with possible synergistic effects. However, the different pharmacokinetic profiles of these two antibiotic classes may not guarantee a concerted spatio-temporal delivery at the site of action, decreasing the efficacy of this combination and promoting resistance. Herein, we propose a multifunctional antibiotic-polymer conjugate, designed to colocalize ampicillin and gentamicin to tackle persistent biofilm infections. The two antibacterial molecules were grafted along with the amino acid l-arginine to a biocompatible polymer backbone with peptidomimetic hydrophilic structure, obtaining the antimicrobial poly(argilylaspartamide-co-aspartic) acid-ampicillin, gentamicin (PAA-AG) conjugate. The PAA-AG conjugate displayed excellent biocompatibility on human cell lines if compared with free drugs, potentially enlarging their therapeutic window and safety, and suitable mucoadhesive characteristics which may help local treatments of mucosal infections. Studies on planktonic cultures of clinical and reference strains of S. aureus, P. aeruginosa, and E. coli revealed that PAA-AG holds a broad-spectrum antibacterial efficacy, revealing high potency in inhibiting the growth of the tested strains. More interestingly, PAA-AG exhibited excellent antibiofilm activity on both Gram+ and Gram- communities, showing inhibition of their formation at subMIC concentrations as well as inducing the regression of mature biofilms. Given the high biocompatibility and broad antibiofilm efficacy, combined with the opportunity for synchronous co-delivery, the PAA-AG conjugate could be a valuable tool to increase the success of ampicillin/gentamicin-based antibiotic multitherapy.

Funding Information: V. Känkänen and H.A. Santos acknowledge Bayer Oy (Finland) for financial support. H.A. Santos acknowledges also the Sigrid Jusélius Foundation and the UMCG Research Fund for financial support. Publisher Copyright: © 2022 The Authors The use of amphiphilic block copolymers to generate colloidal delivery systems for hydrophobic drugs has been the subject of extensive research, with several formulations reaching the clinical development stages. However, to generate particles of uniform size and morphology, with high encapsulation efficiency, yield and batch-to-batch reproducibility remains a challenge, and various microfluidic technologies have been explored to tackle these issues. Herein, we report the development and optimization of poly(ethylene glycol)-block-(ε-caprolactone) (PEG-b-PCL) nanoparticles for intravenous delivery of a model drug, sorafenib. We developed and optimized a glass capillary microfluidic nanoprecipitation process and studied systematically the effects of formulation and process parameters, including different purification techniques, on product quality and batch-to-batch variation. The optimized formulation delivered particles with a spherical morphology, small particle size (dH < 80 nm), uniform size distribution (PDI < 0.2), and high drug loading degree (16 %) at 54 % encapsulation efficiency. Furthermore, the stability and in vitro drug release were evaluated, showing that sorafenib was released from the NPs in a sustained manner over several days. Overall, the study demonstrates a microfluidic approach to produce sorafenib-loaded PEG-b-PCL NPs and provides important insight into the effects of nanoprecipitation parameters and downstream processing on product quality.

Background & aims: Gold nanoparticles (AuNPs) are useful tools for noninvasive drug delivery. AuNP nebulization has shown poor deposition results, and AuNP tracking postadministration has involved methods inapplicable to clinical settings. The authors propose an intratracheal delivery method for minimal AuNP loss and computed tomography scans for noninvasive tracking. Materials & methods: Through high-frequency and directed nebulization postendotracheal intubation, the authors treated rats with AuNPs. Results & conclusion: The study showed a dose-dependent and bilateral distribution of AuNPs causing no short-term distress to the animal or risk of airway inflammation. The study demonstrated that AuNPs do not deposit in abdominal organs and show targeted delivery to human lung fibroblasts, offering a specific and noninvasive strategy for respiratory diseases requiring long-term therapies.

Inspired by natural resources, such as peptides and carbohydrates, glycopolypeptide biopolymer has recently emerged as a new form of biopolymer being recruited in various biomedical applications. Glycopolypeptides with well-defined secondary structures and pendant glycosides on the polypeptide backbone have sparked lots of research interest and they have an innate ability to self-assemble in diverse structures. The nanostructures of glycopolypeptides have also opened up new perspectives in biomedical applications due to their stable three-dimensional structures, high drug loading efficiency, excellent biocompatibility, and biodegradability. Although the development of glycopolypeptide-based nanocarriers is well-studied, their clinical translation is still limited. The present review highlights the preparation and characterization strategies related to glycopolypeptides-based copolymers, followed by a comprehensive discussion on their biomedical applications with a specific focus on drug delivery by various stimuli-responsive (e.g., pH, redox, conduction, and sugar) nanostructures, as well as their beneficial usage in diagnosis and regenerative medicine.

Objectives To develop a sustained release 5-fluorouracil (5-FU) implant by three-dimensional (3D) printing to effectively prevent conjunctival fibrosis after glaucoma surgery. Methods 3D-printed implants composed of polycaprolactone (PCL) and chitosan (CS) were fabricated by heat extrusion technology and loaded with 1% 5-FU. Light microscopy and scanning electron microscopy were used to study the surface morphology. The 5-FU concentration released over 8 weeks was measured by ultraviolet visible spectroscopy. The effects on cell viability, fibroblast contractility and the expression of key fibrotic genes were assessed in human conjunctival fibroblasts. Key findings The PCL–CS-5-FU implant sustainably released 5-FU over 8 weeks and the peak concentration was over 6.1 μg/ml during weeks 1 and 2. The implant had a smooth surface and its total weight decreased by 3.5% after 8 weeks. The PCL–CS–5-FU implant did not affect cell viability in conjunctival fibroblasts and sustainably suppressed fibroblast contractility and key fibrotic genes for 8 weeks. Conclusions The PCL–CS–5-FU implant was biocompatible and degradable with a significant effect in suppressing fibroblast contractility. The PCL–CS–5-FU implant could be used as a sustained release drug implant, replacing the need for repeated 5-FU injections in clinic, to prevent conjunctival fibrosis after glaucoma surgery.

Nanomedicine has emerged as an area of research that has earned a lot of attention in the past decade along with frequent and sustained advancements leading to its extensive plethora of biomedical applications. Following the same, the drug carrier systems like gold nanoparticles (AuNPs) have become the success stories with many marketed formulations now and has proved to be a most suitable answer to the drug delivery concers due to their exclusive electrical and optical properties. They serve as one of the best surfaces to either adsorb, attach, or conjugate and exhibit remarkable optoelectronic, physicochemical, morphological and functional properties. In this study, Gabapentin (GBP) a known FDA approved anti-epileptic drug is selected for improving its pharmaceutical limitations and we have synthesized monodispersed AuNPs for GBP conjugation using citrate reduction method. Here the research group has modified AuNP surfaces with three different thiol moieties namely, Mercaptopropionic acid (3-MPA), 11-Mercaptoundecanoic acid (11-MUA) and the amino acid L-Cysteine (L-Cys) and then attached the GBP with these linkers. The synthesized GBP–AuNP nano-conjugate moieties were further characterized and tested for their in-vitro cytotoxicity, release kinetics and stability properties. The in-vitro release kinetics and cytotoxicity (MTT-Assay) analysis of the formulated GBP–AuNP nano-conjugates along with all the 3 types of linkers was carried out and after the data analysis for the same, it was observed that the GBP–AuNP nano-conjugate with L-Cys linker exhibited the sustained release pattern and non- significant cytotoxicity followed by MUA and MPA, respectively. Moreover, the assessment of GBP-AuNPs evaluated through the comprehensive release kinetics analysis, reinforced the GBP-thiol linkers as potentially more effective and competent than GBP alone. Furthermore, all the experimental data was validated by statistical method, and it can be concluded from the present study that the symmetrical monodispersed AuNPs formulation coated with stable functionalized thiol layer were synthesized with minimal cytotoxicity and can be further explored as an efficient drug delivery system for therapeutic application.

Membrane fusion is a critical step for many essential processes, from neurotransmission to fertilization. For over 40 years protein-free fusion driven by calcium or other cationic species has provided a simplified model of biological fusion, but the mechanisms remain poorly understood. Cation-mediated membrane fusion and permeation are essential in their own right to drug delivery strategies based on cell-penetrating peptides or cation-bearing lipid nanoparticles. Experimental studies suggest calcium drives anionic membranes to a hemifused intermediate which constitutes a hub in a network of pathways, but the pathway selection mechanism is unknown. Here we develop a mathematical model that identifies the network hub as a highly dynamical hemifusion complex. Multivalent cations drive expansion of this high tension hemifusion interface between interacting vesicles during a brief transient. The fate of this interface determines the outcome, either fusion, dead-end hemifusion or vesicle lysis. The model reproduces the unexplained finding that calcium-driven fusion of vesicles with planar membranes typically stalls at hemifusion, and we show the equilibrated hemifused state is a novel lens-shaped complex. Thus, membrane fusion kinetics follow a stochastic trajectory within a network of pathways, with outcome weightings set by a hemifused complex intermediate.SignificanceCells use multicomponent machineries to fuse membranes for neurotransmitter and hormone release and other fundamental processes. Protein-free fusion using calcium or other multivalent cationic fusogens has long been studied as a simplifying model. Cation-mediated membrane fusion or permeation are key events for a number of current drug delivery strategies. However, the mechanisms determining outcomes are unknown. Here we develop a mathematical model that identifies a dynamic hemifusion complex as the decision hub that stochastically sets the outcome in a network of pathways. Cations transiently grow a high tension hemifusion interface between membrane-enclosed compartments, whose fate governs whether fusion, dead-end hemifusion or vesicle lysis occurs. The model provides a systematic framework to predict outcomes of cationic fusogen-mediated interactions between membrane-enclosed compartments.

In the treatment of acute lymphoblastic leukemia, 6-mercaptopurine (6-MP) is commonly used. Yet, short half-life in plasma, poor water solubility, severe side effects and variable bioavailability limit its use. GSH-responsive prodrugs (3&5) and biotin receptor targeted were made to enhance the intracellular accumulation related to 6-MP in the cancer cell. In compound 5, nanoparticles (NPs) have been prepared through conjugating 6-MP to carbon dots (nanocarriers) through GSH-sensitive carbonyl vinyl sulfide linkage, and surface decoration with biotin. Compound 3 was synthesized by direct conjugation of 6-MP to the biotin through GSH-sensitive linkage. In-vitro drug release study of NPs showed good stability in the phosphate buffer saline (PBS), which contains 100 µM GSH at (pH 7.40). Yet, the cumulative rate of the drug release that is associated with samples that contain the GSH medium of 10 mM reached 79.6% in acetate buffer at (pH 5.8). In vitro cytotoxicity study (MTT assay) demonstrated that compound 3 showed higher inhibition ratios on biotin receptor overexpressed cell lines (MCF-7, HepG2) and lower cytotoxicity on normal cell lines (CHO). Compound 5 showed good activity, comparable to 6-MP against (MCF-7, HepG2), and much lower cytotoxicity on (CHO).

Background: Triple-negative breast cancer (TNBC) is the most aggressive type of breast cancer with enhanced metastasis and poor survival. Though chemotherapy, radiotherapy, photothermal therapy (PTT), photodynamic therapy (PDT), and gene delivery are used to treat TNBC, various side effects limit these therapeutics against TNBC. In this review article, we have focused on the mechanism of action of gold nanoparticles (AuNPs) to enhance the efficacy of therapeutics with targeted delivery on TNBC cells. Methods: Research data were accumulated from PubMed, Scopus, Web of Science, and Google Scholar using searching criteria “gold nanoparticles and triple-negative breast cancer” and “gold nanoparticles and cancer”. Though we reviewed many old papers, the most cited papers were from the last ten years. Results: Various studies indicate that AuNPs can enhance bioavailability, site-specific drug delivery, and efficacy of chemotherapy, radiotherapy, PTT, and PDT as well as modulate gene expression. The role of AuNPs in the modulation of TNBC therapeutics through the inhibition of cell proliferation, progression, and metastasis has been proved in vitro and in vivo studies. As these mechanistic actions of AuNPs are most desirable to develop drugs with enhanced therapeutic efficacy against TNBC, it might be a promising approach to apply AuNPs for TNBC therapeutics. Conclusion: This article reviewed the mechanism of action of AuNPs and their application in the enhancement of therapeutics against TNBC. Much more attention is required for studying the role of AuNPs in developing them either as a single or synergistic anticancer agent against TNBC.

The majority of formulations available so far are used in oral forms despite of several pharmaceutical challenges, as this route is the most convenient way of drug delivery. Equally, it necessitates the required need of dose optimization for reduced toxic effects and dosing frequency. Therefore, in this study, we have conceptualized the fabrication of gastro-retentive microspheres of Tinidazole by using a variable drug and ethyl cellulose ratios that will enhance its gastric absorption, retention time along with the sustained pharmacological activity. The scanning electron microscopy and micrometrical studies exhibited their smooth, spherical surface with the particle size range of 244–294 µm. Further, they were floated successfully on the fluid due to their low bulk density and provided the sustained release in simulated gastric fluid, suggesting their suitable gastro-retentive behavior in-vivo. Thus, the prepared formulation proved to be a better gastro-retentive drug delivery system with sustained release, thereby reducing dosing frequency and side effects.

Biotechnology associated with medical technology has allowed biodegradable synthetic polymers to have versatile and diversified biomedical applications due to interesting properties such as good cell adhesion, in vivo proliferation, and degradation without harmful effects to the human body. Thus, they are suitable for a variety of applications, especially those related to therapeutics or pharmaceutics, for example, tissue engineering and drug delivery. This work aimed to revise the broad applications of the term biodegradation in different areas of science. We focused on the most recent biomedical applications of biodegradable synthetic polymers, revising the characteristics which have contributed to solving health-related problems. Actual, efficient, and consistent results have been introduced in the market as a result of the growing search for new technologies. They have been applied both at macro and nanometer scales, in isolated and conjugated forms, or even as encapsulating matrices. Biodegradable synthetic polymers present longer degradation periods when compared to natural polymers, they stand out in tissue engineering since they can be adjusted according to their composition, reaching various degrees of selectivity for specific clinical applications.

Hydrogels have become advantageous materials used in biomedical applications as catheter, soft contact lenses or drug carrying vehicle due to their advantageous features like biocompatibility, insoluble property in aqueous solutions, their resistance to environmental conditions like pH, temperature. Periodontitis is an inflammatory disease which leads to the loss of tissue attachment, gingival recession, tooth loss or periodontal pocket formation. In this study, it was aimed to develop antibiotic loaded hydrogels composed of HEMA and EGDMA for the possible treatment of periodontitis. The in vitro drug delivery characteristics were determined with amoxicillin, which was selected as a proper antibiotic sample for the treatment of periodontitis. In conclusion, the H1 named hydrogel sample was proven to have a possible performance as an amoxicillin reservoir.

2D nanomaterial phosphorene is a chemistically stable, biocompatible, and biodegradable drug delivery platform. This study investigates the drug loading efficiency of phosphorene for the cardiovascular drug carvedilol using density-functional theory (DFT). In the gas phase, carvedilol prefers to interact with phosphorene via P-H bonding with an adsorption energy of 0.59 eV (0.45 eV in water). The complex HOMO–LUMO energy gap has been calculated in gas and solvent media to assess phosphorene-carvedilol reactivity. As compared to free carvedilol and phosphorene, the phosphorene-carvedilol complex has increased solubility. The NCI analysis visualises non-covalent interactions within complexes. The low Van der Waals interactions between carvedilol and phosphorene allow for easy drug offloading. The phosphorene-carvedilol complex is more soluble in water than previously thought. Phosphorene's electron density changes significantly after complex formation, as revealed by charge decomposition plots and electron-localization function plots. PET (photo-induced electron transfer) analysis explains quenching.

The major requirement for a dosage form to be successful is its ability to penetrate the site of application and the bioavailability of the drug released from the dosage form. The buccal drug delivery is an influential route to deliver the drug into the body. Here, in this context, various novel approaches that include lipoidal carriers like ethosomes, transferosomes, niosomes etc and electrospun nanofibers are discussed, with respect to buccal drug delivery. These carriers can be easily incorporated into buccal dosage forms like patches and gels that are responsible for increased permeation across the buccal epithelium. The in vivo methods of evaluation on animal models are conscribed here. The novel biocarriers of lipoidal and non-lipoidal nature can be utilized by loading the drug into them, which are helpful in preventing drug degradation and other drawbacks as compared to conventional formulations. The globally patented buccal formulations give us a wide context in literature about the patents filed and granted in the recent years. When it comes to patient compliance, age is an issue, which is also solved by the buccal route. The pediatric buccal formulations are researched for the customization to be delivered to children. Diseases like mouth ulcers, oral cancer, Parkinson’s disease, aphthous stomatitis etc. have been successfully treated through the buccal route, which infers that the buccal drug delivery system is an effective and emerging area for formulation and development in the field of pharmaceutics.

Background: Nanotechnology is the need of the hour! The design of nanotechnologyaided carriers as a tool for the delivery of low solubility molecules offers a potential platform to overcome the issues of current clinical treatment and achieve good targeted release and bioaccessibility. Objective: Nanosponges (NS) encapsulate types of nanocarriers capable of carrying both lipophilic and hydrophilic substances. They are synthesized by mixing a solution of polyester, which is biodegradable, with cross-linkers. These tiny, porous structures are round-shaped, having multiple cavities wherein drugs can be housed to offer programmable release. Method: The detailed literature review and patent search summarize the ongoing research on NS. Substances such as poorly soluble drugs, nutraceuticals, gases, proteins and peptides, volatile oils, genetic material, etc., can be loaded on these novel carriers, which are characterized using various analytical techniques. Target-specific drug delivery and controlled drug release are the advantages offered by NS, along with a myriad of other promising applications. Results: This review stresses the development of cyclodextrin-based NS, the synthetic methods and characterization of NS, along with factors affecting NS formation, their applications and information on the patented work in this area. NS are solid in character and can be formulated in various dosage forms, such as parenteral, topical, oral or inhalation. Conclusion: Therefore, owing to their promising benefits over other nanocarriers in terms of drug loading, adaptability, sustainability, solubility and tailored release profile, NS is an immediate technological revolution for drug entrapment and as novel drug carriers.The authors expect that these fundamental applications of NS could help the researchers to develop and gain insight about NS in novel drug delivery applications.

The positive charge on liposome surface is known to promote the crossing of the Blood brain barrier (BBB). However, when diastereomeric cationic gemini amphiphiles are among lipid membrane components, also the stereochemistry may affect the permeability of the vesicle across the BBB.Liposomes featuring cationic diasteromeric gemini amphiphiles were formulated, characterized, and their interaction with cell culture models of BBB investigated.Liposomes featuring the gemini amphiphiles were internalized in a monolayer of brain microvascular endothelial cells derived from human induced pluripotent stem cells (hiPSC) through an energy dependent transport, internalization involving both clathrin- and caveolae-mediated endocytosis. On the same formulations, the permeability was also evaluated across a human derived in vitro BBB transport model. The permeability of liposomes featuring the gemini amphiphiles was significantly higher compared to that of neutral liposomes (DPPC/Cholesterol), that were not able to cross BBB. Most importantly, the permeability was influenced by the stereochemistry of the gemini and pegylation of these formulations did not result in a drastic reduction of the crossing ability. The in vitro iPSC-derived BBB models used in this work represent an important advancement in the drug discovery research of novel brain delivery strategies and therapeutics for central nervous system diseases.

Lipid rafts are highly ordered regions of the plasma membrane enriched in signaling proteins and lipids. Their biological potential is realized in exosomes, a subclass of extracellular vesicles (EVs) that originate from the lipid raft domains. Previous studies have shown that EVs derived from human placental mesenchymal stromal cells (PMSCs) possess strong neuroprotective and angiogenic properties. However, clinical translation of EVs is challenged by very low, impure, and heterogeneous yields. Therefore, in this study, lipid rafts are validated as a functional biomaterial that can recapitulate the exosomal membrane and then be synthesized into biomimetic nanovesicles. Lipidomic and proteomic analyses show that lipid raft isolates retain functional lipids and proteins comparable to PMSC-EV membranes. PMSC-derived lipid raft nanovesicles (LRNVs) are then synthesized at high yields using a facile, extrusion-based methodology. Evaluation of biological properties reveals that LRNVs can promote neurogenesis and angiogenesis through modulation of lipid raft-dependent signaling pathways. A proof-of-concept methodology further shows that LRNVs could be loaded with proteins or other bioactive cargo for greater disease-specific functionalities, thus presenting a novel type of biomimetic nanovesicles that can be leveraged as targeted therapeutics for regenerative medicine.

Cancer is known as one of the leading causes of morbidity and fatality, currently faced by our society. The prevalence of cancer related dieses is rapidly increasing around the world. To reduce the mortality rates, early diagnosis and subsequent treatment of cancer in timely manner is quite essential. Advancements have been made to achieve effective theranostics strategies to tackle cancerous dieses, yet very challenging to overcome this issue. Recently, advances made in the field of nanotechnology have shown tremendous potential for cancer theranostics. Different types of nanomaterials have been successfully employed to develop sophisticated diagnosis and therapy techniques. In this context, graphene and its derivatives e.g. graphene oxide (GO) and reduced graphene oxide (RGO) have been investigated as promising candidates to design graphene-based nanosystems for the diagnosis and therapeutic purpose. Further, to synthesize graphene and its derivatives different types of physicochemical methods are being adopted. However, each method has its own advantage and disadvantages. In this reference, among diverse biological methods, microbial technique can be one of the most promising and eco-friendly approach for the preparation of graphene and its derivatives, particularly GO and RGO. In this review, we summarize studies performed on the preparation of graphene and its derivatives following microbial routes meanwhile focus has been made on the preparation method and the possible mechanism involved therein. Thereafter, we have discussed applications of graphene and its derivatives to developed advanced nanosystem that can be imperative for the cancer theranostics. Results of recent studies exploring applications graphene based nanosystem for the preparation of different types of biosensors for early diagnosis; advanced therapeutic approaches by designing drug delivery nanosystems along with multifunctionality (e.g cancer imaging, drug delivery, photodynamic and photo thermal therapy) in cancer theranostics have been discussed. Particularly, emphasis has been given on the preparation techniques of graphene based nanosystems, being employed in designing of biosensing platforms, drug delivery and multifunctional nanosystems. Moreover, issues have been discussed on the preparation of graphene and its derivatives following microbial technique and the implementation of graphene based nanosystems in cancer theranostics.

Colorectal Cancer (CRC) is one of the leading causes of cancer-related deaths worldwide. Despite the notable advances achieved over the last few decades, CRC remains a hard-to-treat deadly disease in many patients. This is attributed mainly to chemo- and immuno-resistance, which frequently emerge soon after treatment with conventional therapeutics. Systemic treatments are also constrained by their many undesired and serious side effects. More recently, nanomedicine has emerged as an attractive modality that can overcome issues of therapeutic resistance, improper delivery, or suboptimal targeting of tumor cells. Many nanomaterials, having already been examined in pre-clinical and clinical studies, are now considered biocompatible and relatively safe. Indeed, around 50 nano-formulations have so far been approved as diagnostic and therapeutic agents in humans. Here, in this review, we describe a set of imperative nanoparticles (NPs) involved in diagnosing and treating CRC. In particular, we discuss the theragnostic roles of quantum dots, iron oxide NPs, Polylactide-co-glycolic acid (PLGA) NPs, dendrimer NPs, carbon nanotubes, liposomes, and gold NPs. We dissect the molecular and clinical evidence supporting the use of these NPs in CRC. We also highlight their implications in targeted drug delivery as well as their anti-tumorigenic properties and effects on the cardinal hallmarks of CRC. We conclude by highlighting the notion that nanomedicine is emerging as an attractive approach to address the unmet needs in managing several diseases, including CRC.

A self-regulated anti-diabetic drug release device mimicking pancreatic cells is highly desirable for the therapy of diabetes. Herein, a glucose-mediated dual-responsive drug delivery system, which combines pH- and H2O2-responsive block copolymer grafted hollow mesoporous silica nanoparticles (HMSNs) with microneedle (MN) array patch, has been developed to achieve self-regulated administration. The poly[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl acrylate]-b-poly[2-(dimethylamino)ethyl methacrylate] (PPBEM-b-PDM) polymer serves as gate keeper to prevent drug release from the cavity of HMSNs at normoglycemic level. In contrast, the drug release rate is significantly enhanced upon H2O2 and pH stimuli due to the chemical change of H2O2 sensitive PPBEM block and acid responsive PDM block. Therefore, incorporation of anti-diabetic drug and glucose oxidase (GOx, which can oxidize glucose to gluconic acid and in-situ produce H2O2) into stimulus polymer coated HMSNs results in a glucose-mediated MN device after depositing the drug-loaded nanoparticles into MN array patch. Both in vitro and in vivo results show this MN device presents a glucose mediated self-regulated drug release characteristic, which possesses a rapid drug release at hyperglycemic level but retarded drug release at normoglycemic level. The result indicates that the fabricated smart drug delivery system is a good candidate for the therapy of diabetes.

Introduction: The plant used in the present study is Cassia fistula, which belongs to the family Leguminosae and has been used in traditional medicinal systems due to the presence of a copious amount of Phytochemicals with various properties. Aims: This study is focused on the extraction of phytochemicals from the Cassia fistula flower and its subsequent encapsulation into chitosan matrix for applications in drug delivery. Chitosan is approved by FDA for its use in Pharmaceutical industries. Methods: As described by several analytical techniques such as FT-IR, NMR, Thermal analysis, and SEM, the microsphere thus prepared by the current study is predicted to release the desired extract with medicinal properties in a controlled manner, allowing for more convenient and desired levels of drug administration. The swelling study and release study of the prepared microsphere have been carried out in physiological pH 2 and 7.4. NMR study has shown that sitosterol and friedelin have been encapsulated successfully into the chitosan matrix. Results: The microspheres have shown up to 80% swelling in pH 2 upto 8 days, and 60% of the in- -vitro controlled drug release has also been found in pH 2 upto 2 days. The thermal studies using TGA and DSC supported the thermal stabilities of CS beads, CFFE and CFFE-CS beads, Also, it showed the dispersion of the CFFE in the cavities of the Chitosan matrix. Conclusion: The Biomedical application of the synthesized CFFE-CS beads has also been reported on the basis of their antibacterial studies.

The use of graphene quantum dots as biomedical devices and drug delivery systems has been increasing. The nano-platform of pure carbon has shown unique properties and is approved to be safe for human use. In this study, we successfully produced and characterized folic acid-functionalized graphene quantum dots (GQD-FA) to evaluate their antiviral activity against Zika virus (ZIKV) infection in vitro, and for radiolabeling with the alpha -particle emitting radionuclide radium-223. The in vitro results exhibited the low cytotoxicity of the nanoprobe GQD-FA in Vero E6 cells and the antiviral effect against replication of the ZIKV infection. In addition, our findings demonstrated that functionalization with folic acid doesn't improve the antiviral effect of graphene quantum dots against ZIVK replication in vitro. On the other hand, the radiolabeled nanoprobe 223Ra@GQD-FA was also produced as confirmed by the Energy Dispersive X-Ray Spectroscopy analysis. 223Ra@GQD-FA might expand the application of alpha targeted therapy using radium-223 in folate receptor-overexpressing tumors., Carlos Chagas Filho Foundation for Research Support of Rio de Janeiro State (FAPERJ) [E-26/200.815/2021, E-26/010.000981/2019, E-26/010.002362/2019, E-26/211.269/2021, E-26//211.207/2021, E-26/202.320/2021]; CNPq [301069/2018-2]; National Nuclear Energy Commission [01341.011064/2021-71], This study was funded by Carlos Chagas Filho Foundation for Research Support of Rio de Janeiro State (FAPERJ) (Cientista do Nosso Estado: E-26/200.815/2021; Rede NanoSaude: E-26/010.000981/2019, Pesquisa na UEZO: E-26/010.002362/2019; Tematicos: E-26/211.269/2021, Infraestrutura e Pesquisa na UEZO e UERJ: E-26//211.207/2021, Bolsa de Pos Doutorado Senior (PDS): E-26/202.320/2021) CNPq (Bolsa de Produtividade 1B: 301069/2018-2) to Ralph Santos-Oliveira. National Nuclear Energy Commission (Bolsa de Posdoutorado CNEN: 01341.011064/2021-71) to Martha Sahyli Ortega Pijeira.

Extracellular vesicles (EVs) are the substances that are conveyed by most sorts of cell, which play a critical role in cell-to-cell communication. Exosomes are among the most commonly explored EVs. Exosomes contain lipids, RNAs and proteins. Many examinations have shown that exosomes derived from cells play different biological roles in normal as well as diseased condition. Recent investigations have explored exosomes as natural drug delivery vehicles, as they have ability to deliver different cargo to nearby and targeted cells with high specificity and efficiency. In the last decade, there has been increased interest in exosomes research due to their potential role in disease diagnosis as intercellular messengers. Exosomes have potential in targeted drug/gene delivery, due to their unique properties, such as low immunogenicity, excellent tissue/cell penetration capacity and innate stability. As a result, exosomes can be used for disease detection and for various treatments. In this review, we focus on the potential use of exosomes as valuable diagnostic and prognostic biomarkers for their cell-lineage and state-specific contents, and their possible use as therapeutic vehicle for drug and gene delivery. As a drug, exosomes have a variety of applications in various diseases.

Cutaneous leishmaniasis (CL) and mucocutaneous leishmaniasis (ML) show clinical spectra that can range from a localized lesion (with a spontaneous healing process) to cases that progress to a generalized systemic disease with a risk of death. The treatment of leishmaniasis is complex since most of the available drugs show high toxicity. The development of an effective topical drug formulation for CL and ML treatment offers advantages as it will improve patient’s compliance to the therapy given the possibility for self-administration, as well as overcoming the first pass metabolism and the high costs of currently available alternatives. The most common dosage forms include solid formulations, such as membranes and semi-solid formulations (e.g., ointments, creams, gels, and pastes). Topical treatment has been used as a new route of administration for conventional drugs against leishmaniasis and its combinations, as well as to exploit new substances. In this review, we discuss the advantages and limitations of using topical drug delivery for the treatment of these two forms of leishmaniasis and the relevance of combining this approach with other pharmaceutical dosage forms. Emphasis will also be given to the use of nanomaterials for site-specific delivery., Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES), Fundacao de Amparo a Pesquisa do Estado do Sergipe (FAPITEC) 88887.159533/2017-00, Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPQ) CNPq 301964/2019-0 01/2019 06/2019, Fundacao Carolina

Tuberculosis, caused by Mycobacterium tuberculosis, is a disease long dealt with, but still remains the second leading cause of death world-wide. The current anti-tubercular chemotherapy primarily targets the microbial pathogenesis, which however, is failing due to the development of drug resistance. Moreover, with fewer new drugs reaching the market, there is a need to focus on alternate treatment approaches that could be used as stand-alone or adjunct therapy and the existing drugs, referred to as Track II chemotherapy. This article is an attempt to review the changing global patterns of tuberculosis and its treatment. Further, newer drug delivery approaches like multi-particulate drug carriers which increase the therapeutic efficacy and bring down the systemic toxicity associated with drugs have also been discussed. There is also a need to use interventions which can be used as Track II therapy. Host-directed therapeutics (HDT) is an emerging area concept in which host cell functions and hence the response to pathogens can be modulated, which can help manage TB. HDT decreases damage induced due to inflammation and necrosis in the lungs and other parts of the body due to the disease. Various immuno-modulatory pathways have been discussed in this review which could be explored further to treat TB. An in-depth understanding of multi-particulate drug carriers and HDT could help in dealing with tuberculosis; however, there is still a long way to go.

Introduction: Skin is the largest organ of the human body protecting the underlying organs and tissues from any foreign attack. Any damage caused in the skin may sometimes result in serious consequences within the internal body tissues. Burn is one such issue that damages the layers of the skin and thereby making the skin vulnerable and prone to any foreign matter entering and causing serious diseases. Methods: An online literature assessment was steered for the lipid nanoparticles, burn wound treatments, and different types of nanoformulation. Appropriate information was taken from different electronic scientific databases such as Web of Science, Elsevier, Science Direct, Springer, PubMed, Google Scholar etc. Additional data was summarized from textbooks, local prints and scripts. Results: Recent innovations and developments in nanotechnology-based drug delivery systems have shown promising results in minimizing the drawbacks associated with conventional therapies. Lipid based nanoparticles possess capabilities to deliver active agents to their target site without the possibility of degradation. Conventional therapy of burn wound is costly and the treatment is long lasting, making the patient uncomfortable. Moreover, it also doesn’t yield satisfactory results or narrow effects. Encapsulation of bioactives inside the lipid core protects the active entity from pH and enzymatic degradations. Conclusion: This review highlights the drawbacks associated with conventional dosage forms. A lot of consideration is focused on the advancement of nanomaterials using innovative methods in wound care for treating burn wounds with a faster healing effect. This review article highlights recent developments in lipid based nanoformulations for the treatment of burn wound injury.

S and N-doped carbon dots (S-CDs and N-CDs) and their cisplatin (cis-Pt) derivatives. (S-CDs@cis-Pt and N-CDs@cis-Pt) were tested on two ovarian cancer cell lines: A2780 and A2780 cells resistant to cis-Pt (A2780R). Several spectroscopic techniques were employed to check S-CDs@cis-Pt and N-CDs@cis-Pt: solid- and solution-state nuclear magnetic resonance, matrix-assisted laser desorption, ionization time-of-flight mass spectrometry, and X-ray photoelectron spectroscopy. In addition, synchrotron-based Fourier Transformed Infrared spectro-microscopy was used to evaluate the biochemical changes in cells after treatment with cis-Pt, S-CDs, N-CDs, or S-CDs@cis-Pt and N-CDs@cis-Pt, respectively. Computational chemistry was applied to establish the model for the most stable bond between S-CDs and N-CDs and cis-Pt. The results revealed the successful modification of S-CDs and N-CDs with cis-Pt and the formation of a stable composite system that can be used for drug delivery to cancer cells and likewise to overcome acquired cis-Pt resistance. Nanoparticle treatment of A2780 and A2780R cells led to the changes in their structure of lipids, proteins, and nucleic acids depending on the treatment. The results showed the S-CDs@cis-Pt and N-CDs@cis-Pt might be used in the combination with cis-Pt to treat the adenocarcinoma, thus having a potential to be further developed as drug delivery systems.

Introduction Temporomandibular-joint osteoarthritis (TMJOA) management is a major challenge. Minimally invasive therapies (based mainly on injections) have been developed to increase local efficacy and limit adverse systemic effects. However, the requirement for repeat injections due to a short duration of action and expensive healthcare costs have pushed researchers to develop, via tissue engineering, drug-delivery systems (DDSs). In this literature systematic review, we aim to provide an overview of studies that tested DDSs on a TMJOA model. Material and methods We searched on PubMed for articles published from November 1965 to March 2021 on DDSs using a TMJOA model. We highlighted the different DDSs and the active molecule employed. Route of drug administration, model type, test duration, and efficacy duration were assessed. To evaluate the quality of each study, a protocol bias was tested using QUADAS-2™. Results Of the 10 studies that were full text-screened, four used a poly(lactic-co-glycolic acid)-based delivery system. The other DDSs employed chitosan-based hydrogels, microneedles patches, nanostructured lipid carriers, or poloxamer micelles. Hyaluronic acid, nonsteroidal anti-inflammatory drugs, and analgesics were used as active molecules in five studies. The main way to administer DDSs was intra-articular injection and the most used model was the rat. Discussion Various DDSs and active molecules have been studied on a TMJOA model that could aid TMJOA management. Further works using longer test durations are necessary to validate these advances.

Modern society is faced with an important challenge – how to ensure enough energy and resources for industrial and population growth and preserve the environment at the same time? The answer lies in the development of novel technologies based on eco-friendly and low-cost materials. In the field of new materials, perovskite oxides stand out due to their multiple properties contained in a single material. The most important are electrical, magnetic and catalytic properties which are the basis for their practical applications. Perovskites were widely investigated over the last 70 years, but perovskite-based technologies have still not reached commercialization. This review presents several novel perovskite-based technologies and addresses possible issues and opportunities for their implementation, based on the recent scientific discoveries.

Metal–organic frameworks are porous polymeric materials formed by linking metal ions with organic bridging ligands. Metal–organic frameworks are used as sensors, catalysts for organic transformations, biomass conversion, photovoltaics, electrochemical applications, gas storage and separation, and photocatalysis. Nonetheless, many actual metal–organic frameworks present limitations such as toxicity of preparation reagents and components, which make frameworks unusable for food and pharmaceutical applications. Here, we review the structure, synthesis and properties of cyclodextrin-based metal–organic frameworks that could be used in bioapplications. Synthetic methods include vapor diffusion, microwave-assisted, hydro/solvothermal, and ultrasound techniques. The vapor diffusion method can produce cyclodextrin-based metal–organic framework crystals with particle sizes ranging from 200 nm to 400 μm. Applications comprise food packaging, drug delivery, sensors, adsorbents, gas separation, and membranes. Cyclodextrin-based metal–organic frameworks showed loading efficacy of the bioactive compounds ranging from 3.29 to 97.80%.

Both innate and adaptive immune systems play a crucial role in the pathology of skin diseases. To control these cells, there is a need for transdermal drug delivery systems that can target multiple cell populations at independently tunable rates. Herein, we describe a tissue-adhesive hydrogel system that contains particles capable of regulating the release of small molecule drugs at defined rates. Resiquimod (a macrophage-targeting drug) and palbociclib (a T cell-targeting drug) are encapsulated within two types of silicone particles embedded within the hydrogel. We demonstrate that drug release is mediated by the crosslink density of the particles, which is decoupled from the bulk properties of the hydrogel. We show that this system can be used to sustainably polarize macrophages toward an anti-tumor phenotype in vitro and ex vivo, and that the hydrogels can remain attached to skin explants for several days without generating toxicity. The hydrogel system is compatible with standard dermatological procedures and allows transdermal passage of drugs. The multimodal, tunable nature of this system has implications in treating a variety of skin disorders, managing infections, and delivering vaccines. STATEMENT OF SIGNIFICANCE: We describe a tissue-adhesive hydrogel that can regulate the release of drugs in a manner that is decoupled from its bulk properties. The mechanism of drug release is mediated by embedded microparticles with well-defined crosslink densities. The significance of this system is that, by encapsulating different drugs into the particles, it is possible to achieve multimodal drug release. We demonstrate this capability by releasing two immunomodulatory drugs at disparate rates. A drug that targets innate immune cells is released quickly, and a drug that targets adaptive immune cells is released slowly. This programmable system offers a direct means by which cellular responses can be enhanced through independent targeting for a variety of transdermal applications, including cancer treatment and vaccine delivery.

Aims and objectives: In this study, an attempt was made to synthesize, characterize, and develop many applications of functionalized rare metal oxide nanoparticles. Herein, a new strategy for drug delivery is developed to functionalize magnetite nanoparticles to improve their performances in the delivery of celecoxib. Materials and methods: Magnetite Fe3O4@SiO2 nanoparticles are synthesized by the sol-gel method. The surface of the hydroxyl groups was extended by treating with cerium nitrate salt; finally, sodium hydroxide was anchored to the surface hydroxyl groups to produce cerium oxidefunctionalized Fe3O4@SiO2@CeO2 magnetic nanoparticles (FSC). The synthesized sample was characterized by FT-IR, FESEM, VSM, TGA, and XRD. Afterward, the functionalized nanoparticles were examined in the delivery of celecoxib as an active drug model involving cerium oxide and hydroxyl functional groups. Results: For this purpose, the amount of loading/release of the drug was investigated in different amounts of nanocomposite and pH values. Conclusion: The results of the present investigation indicate that the formulations (mFSC=5 mg, pH=3.3) can be considered as best among various formulations with respect to particle size, entrapment efficiency, and in-vitro successful drug release.

Smart biomaterials, featuring not only bioactivity, but also dynamic responsiveness to external stimuli, are desired for biomedical applications, such as regenerative medicine, and hold great potential to expand the boundaries of the modern clinical practice. Herein, a magnetically responsive three-dimensional scaffold with sandwich structure is developed by using hydroxyapatite (HA) nanowires and ferrosoferric oxide (Fe3O4) nanoparticles as building blocks. The magnetic HA/Fe3O4 scaffold is fully inorganic in nature, but shows polymeric hydrogel-like characteristics including a 3D fibrous network that is highly porous (>99.7% free volume), deformable (50% deformation) and elastic, and tunable stiffness. The magnetic HA/Fe3O4 scaffold has been shown to execute multimodal motion upon exposure to an external magnetic field including shape transformation, rolling and somersault. In addition, we have demonstrated that the magnetic scaffold can serve as a smart carrier for remotely controlled, on-demand delivery of compounds including an organic dye and a protein. Finally, the magnetic scaffold has exhibited good biocompatibility, supporting the attachment and proliferation of human mesenchymal stromal cells, thereby showing great potential as smart biomaterials for a variety of biomedical applications.

In this work, the adsorption energies and some of the main electronic properties of selected biological molecules adsorbed onto a (TiO2)20 cluster were studied. With this aim, Density-Functional Theory (DFT) calculations were performed using SIESTA code. The Perdew–Burke–Ernzerhof (PBE) functional within the Generalized Gradient Approximation (GGA) was used for the exchange and correlation potential. For this study, we chose molecules with very different characteristics and applications in everyday life, including antibiotics, anti-inflammatory drugs, vitamins, and so on. The TiO2 substrate was considered due to its harmlessness and versatility of application in various industries. In particular, we studied the changes in some of the main electronic properties of the molecules after adsorption onto titanium dioxide. For all of the molecules studied here, we observed that this substrate can increase the stability of the adsorbed molecules, with values in the range of 12–150 meV/atom. The reliability of our calculations was verified through additional optimizations with other DFT codes, considering the hybrid functionals B3LYP and M06-L. Our results showed a reasonably good agreement among these three functionals, thereby revealing the possibility of adsorption of the selected biological molecules onto the vertex of the TiO2 nanoclusters. Some of these molecules were considered as possible candidates for the delivery of drugs into the SARS-CoV-2 main protease, promoting the inhibition of this virus. We are not aware of any systematic study that has focused on the adsorption of the selected molecules on a (TiO2)20 substrate within the same framework, including the analysis of the differences in electronic properties through the use of different functionals.

Breast-conserving surgery (BCS) is the primary strategy for treating early-stage breast cancer; however, the incidence of local recurrence and breast tissue loss negatively impacts patients and survivors. Furthermore, radiotherapy and/or systemic therapies are frequently advised to avoid recidivism and increase the patient’s chance of survival, resulting in longer duration of treatments, and unpleasant systemic side effects. Given the poor prognosis and the heterogeneity between individuals and tumors, a patient-centered approach is fundamental. Herein we developed a multipurpose 4D printed implant made of a blend of carboxymethyl cellulose sodium salt (CMC) and cellulose nanocrystals (CNC), loaded with doxorubicin (DOX). To predict printability performance, full rheological characterization was carried out. The smart device was programmed to change size, under swelling, to better fit in the tissue cavity, resulting in a great potential for personalization, thus improving the aesthetic outcomes. The influence of the formulation and printing parameters on the morpho transformation was investigated through the swelling test, confirming the possibility to program the 4D shape. The manufactured implants were characterized by a variety of methods, including in vitro release studies. Lastly, the anticancer activity was conducted in vitro, on MDA-MB-231 cells. Implants promoted an anticancer effect of −58% viability after 72 h incubation, even when tested 4 weeks after the printing process. Overall, the morpho transformation and the in vitro studies have shown that the implant could represent a potential strategy for breast cancer following resection, to fill the void in the breast resulting from the surgery and provide an anticancer effect to avoid recurrence.

Metal-organic frameworks (MOFs) are relatively new porous materials that have attracted significant attention in recent decades. Potential applications in gas storage and separation have been at the forefront of this research. Their biomedical applications have also received attention; however, significant work is needed to expand the field. Therefore, the aim of this thesis is to expand our understanding on the biomedical applications of novel MOFs. Chapter 1 provides an introduction into metal-organic frameworks, their properties and applications. It also provides a literature review on the biomedical applications of MOFs, with a particular focus on their drug delivery and MRI applications. Chapter 2 is a published review on the synthesis and biomedical applications of highly porous MOFs. The review defines a highly porous MOF as any MOF with a surface area above 4000 m2 g-1 . Synthetic approaches to highly porous MOFs are classified and discussed in detail. Challenges such as interpenetration and methods of overcoming them are also discussed. The biomedical applications of highly porous MOFs are classified. Highly porous MOFs are unique as their high pore volume allows for the encapsulation of large guest biomolecules such as protein, enzymes, genetic material etc. The ability of the frameworks to load such biomolecules lends to applications in protein crystallisation, biocatalysis and gene therapy. This work has been published in Molecules. 2022; 27(19):6585. Chapter 3 discusses the synthesis of a novel Zn2+ MOF, NUIG4. NUIG4 is a rare example of four-fold interpenetrated pcu MOF. The framework is composed of an octahedral [Zn4O(COO)6] secondary building unit and a linear ditopic 4-((4-carboxybenzylidene)amino)benzoic acid (CBABH2) linker. The structure of the framework was determine by single crystal X-ray diffraction. NUIG4 shows an exceptionally high loading of the anticancer drug doxorubicin (DOX) 1955 mg DOX g-1 . A combination of DFT calculations and solid-state NMR studies indicated the loading is driven by aromatic π–π stacking interactions between DOX and the framework. DOX release from the framework is pH controlled, with substantially more DOX release under acidic conditions. Cytocompatibility studies on human dermal fibroblast cells indicated the framework and linker are both biocompatible. The gas separation potential of the framework was evaluated using individual component adsorption isotherms. NUIG4 displays a rare “inverse selectivity” for C2H2 over CO2. This work was published in J. Mater. Chem. B, 2022,10, 1378-1385. Chapter 4 Discusses the synthesis and characterisation of multivariate (MTV) NUIG4 MOFs. Attempts were made to synthesise nitrated, fluorinated, pyridyl, naphthyl, methylated and hydroxylated analogues of NUIG4. Of these functional groups, only methyl and hydroxyl functionality could be introduced into the framework, at various different ratios, when used in combination with the original CBABH2 linker. Frameworks were also isolated with the CBABH2-OH and CBABH2-CH3 linkers exclusively. The methylated framework and the MTV-NUIG4 frameworks shared the same structure with the parent MOF. There was an observed decrease in framework crystallinity as the degree of functionality increased. The Dox uptake and release of the MTV-NUIG4 MOFs was studied, providing an insight into the effects of functionality on uptake capacity and release. Chapter 5 discusses the synthesis of a family of Ln3+ (Ln = Gd, Tb, Dy) MOFs based on the biocompatible CBABH2 linker. The frameworks are isostructural, featuring rhombic channel-type pores. The Gd analogue (NUIG5-Gd) was loaded with the anti-epilepsy drug carbazmazepine (CBZ) at a loading of 11.6 wt%. The loading occurred in two steps, indicative of the breathing effect. CBZ release takes three days in water and twelve hours in PBS solution. As NUIG5-Gd contains a large number of Gd3+ ions, its potential as a magnetic resonance imaging (MRI) contrast agent was explored. Firstly, the framework was nanosized by treatment with polyvinylpyrrolidone, followed by ultrasonication. Dynamic Light Scattering (DLS) measurements indicated a mean particle size of 229 nm. The relaxivity of the nanoparticles (nano-NUIG5-Gd) was calculated from concentration dependent proton relaxation rates. Nano-NUIG5-Gd displays a longitudinal relaxivity of 9.7 mM-1 s-1 per Gd3+, marginally greater than those of commercial Gd3+ MRI contrast agents. Cytotoxicity studies on nano-NUIG5-Gd indicate the framework is biocompatible, with a cell viability >70% at a concentrations as high as 1 mg mL-1 . Chapter 6 discusses the design and synthesis of novel MOFs for the treatment of tuberculosis. A prodrug linker 4,4’-azodisalicylic acid (AZDH4) was synthesised and combined with divalent metal ions (Mg2+, Zn2+, Cu2+, Co2+) yielding a family of isostructural MOFs (M2(AZD)). The AZDH4 linker is a prodrug, whose metabolic product is para-aminosalicylic acid (ASA), an antitubercular drug. The M2(AZD) frameworks share a topology with the well-studied IRMOF-74 family, featuring 1-dimensional hexagonal channel-type pores. The rate of linker release was studied in water and PBS solution. The frameworks show differing rates of AZD4- in deionised water and PBS solution. The rate of AZD4- release was correlated with metal hardness, with Mg2(AZD) showing a faster release rate than the other frameworks. In order to investigate their dual drug delivery potential, we attempted to load the frameworks with the antitubercular antibiotic isoniazid (INH). Zn2(AZD) and Mg2(AZD) loaded INH at loadings of 4 and 22 wt% respectively. Minimum inhibitory concentration (MIC) assays were carried out to determine the antibacterial activity of the frameworks. This was carried out on Pseudomonas aeruginosa (P. aeruginosa) and Staphylococcus aureus (S. aureus). The frameworks showed no inhibitory effects, this may be due specificity of INH and ASA, as they are used almost exclusively to treat tuberculosis. Interestingly the only framework to show an inhibitory effect is Co2(AZD) likely due to the high toxicity of Co2+ ions towards bacteria. 2025-07-07

The files contain fluorescent images generated in this study.&nbsp

In order to achieve the optimal level of effectiveness and safety of drugs, it is necessary to control the drug release rate. Therefore, it is important to discover the factors affecting release profile from a drug delivery system. Geometry is one of these effective factors for a tablet-shaped drug delivery system. In this study, an attempt has been made to answer a general question of how the geometry of a tablet can affect the drug release profile. For this purpose, the drug release process of theophylline from two hundred HPMC-based tablets, which are categorized into eight groups of common geometries in the production of oral tablets, was simulated using finite element analysis. The analysis of the results of these simulations was carried out using statistical methods including partial least squares regression and ANOVA tests. The results showed that it is possible to predict the drug release profile by knowing the geometry type and dimensions of a tablet without performing numerous dissolution tests. Another result was that, although in many previous studies the difference in the drug release profile from several tablets with different geometries was interpreted only by variables related to the surface, the results showed that regardless of the type of geometry and its dimensions, it is not possible to have an accurate prediction of the drug release profile. Also, the results showed that without any change in the dose of the drug and the ingredients of the tablet and only because of the difference in geometry type, the tablets significantly differ in release profile. This occurred in such a way that, for example, the release time of the entire drug mass from two tablets with the same mass and materials but different geometries can be different by about seven times.

The administration of poorly water-soluble drugs represents a relevant problem due to the low body fluids transport efficiency through hydrophilic hydrogels. Star-shaped co-polymers, i.e., amphiphilic polymers such as those with a hydrophobic core and a hydrophilic outer shell, can be used to improve weak interactions with drugs, with relevant benefits in terms of administration and controlled delivery. In this work, two different co-polymers, four-arm star-shaped PCL–PEG and six-arm star-shaped PCL–PEG, were synthesized via ring-opening polymerization to be loaded with ciprofloxacin. 1H-NMR and FTIR analyses confirmed that PCL arms were successfully grafted to the mPEG backbone, while DSC analysis indicated similar crystallinity and melting point, ranging from 56 to 60 °C, independent of the different co-polymer architecture. Therefore, both star-shaped PCL-PEGs were investigated as cargo device for ciprofloxacin. No significant differences were observed in terms of drug entrapment efficiency (>95%) and drug release, characterized by a pronounced burst followed by a slow sustained release, only slightly affected by the co-polymer architecture. This result was also confirmed with curve fitting via the Korsmeyer–Peppas model. Lastly, good antibacterial properties and biocompatibility exhibited in both star-shaped PCL–PEG co-polymers suggest a promising use for oral delivery applications.

Multistep one-pot polycondensation reactions synthesized amphiphilic diblock polyphosphoesters containing lactic acid units in the polymer backbone. At the first step was synthesized poly[poly(ethylene glycol) H-phosphonate–b-poly(ethylene glycol)lactate H-phosphonate] was converted through one pot oxidation into poly[alkylpoly(ethylene glycol) phosphate-b-alkylpoly(ethylene glycol)lactate phosphate]s. They were characterized by 1H, 13C {H},31P NMR, and size exclusion chromatography (SEC). The effects of the polymer composition on micelle formation and stability, and micelle size were studied via dynamic light scattering (DLS). The hydrophilic/hydrophobic balance of these polymers can be controlled by changing the chain lengths of hydrophobic alcohols. Drug loading and encapsulation efficiency tests using Sudan III and doxorubicin revealed that hydrophobic substances can be incorporated inside the hydrophobic core of polymer micelles. The micelle size was 72–108 nm when encapsulating Sudan III and 89–116 nm when encapsulating doxorubicin. Loading capacity and encapsulation efficiency depend on the length of alkyl side chains. Changing the alkyl side chain from 8 to 16 carbon atoms increased micelle-encapsulated Sudan III and doxorubicin by 1.6- and 1.1-fold, respectively. The results obtained indicate that these diblock copolymers have the potential as drug carriers.

This study reports the fabrication of polymeric matrices through electrospinning using polymethyl methacrylate (PMMA) and poly(lactic-co-glycolic acid) (PLGA), biocompatible polymers commonly used in medical systems. These polymers were combined with an antibacterial drug, sulfadiazine sodium salt (SDS) or its supramolecular system formed with hydroxypropyl-β-cyclodextrin (HPβ/CD) at 1:1 molar ratio, aiming to assemble a transdermal drug delivery system. The formation of fibers was confirmed by scanning electron microscopy (SEM), and the fibers’ surface properties were analyzed using contact angle and water vapor permeability techniques. Drug release tests and cell viability assays were performed to evaluate the potential toxicity of the material. SEM images demonstrated that the obtained fibers had nanoscale- and micrometer-scale diameters in PLGA and PMMA systems, respectively. The contact angle analyses indicated that, even in the presence of hydrophilic molecules (SDS and HPβCD), PMMA fibers exhibited hydrophobic characteristics, while PLGA fibers exhibited hydrophilic surface properties. These data were also confirmed by water vapor permeability analysis. The drug release profiles demonstrated a greater release of SDS in the PLGA system. Moreover, the presence of HPβCD improved the drug release in both polymeric systems and the cell viability in the PMMA SDS/HPβCD system. In terms of antibacterial activity, all membranes yielded positive outcomes; nevertheless, the PLGA SDS/HPβCD membrane exhibited the most remarkable results, with the lowest microbial load values. Additionally, the pseudo wound healing analysis demonstrated that the PLGA SDS/HPβCD fiber exhibited results similar to the control group. Consequently, these findings exemplify the substantial potential of the obtained materials for use in wound healing applications.

Bacterial infections are a constant challenge in the management of acute and chronic wounds. Chronic wounds, such as diabetic foot ulcers, have increased significantly in the last few years due to the rise of an aging population. A better understanding of the infectious pathophysiological mechanisms is urgently needed along with new options for the treatment of wound infections and wound-healing disorders. New advances in the preparation of biocompatible dressing materials that can be loaded with antimicrobial drugs may improve the topical treatment of infected wounds. In this study, we investigated the antimicrobial activity of polyvinylpyrrolidone (PVP) foils loaded with ciprofloxacin (Cipro-foils) in the presence of acetic acid as a co-solvent. We used ex vivo human wounds that were infected with two bacterial strains: methicillin-resistant Staphylococcusaureus (MRSA) or Pseudomonas aeruginosa (PAO1). The effectiveness of the treatment was demonstrated by the quantification of the living bacteria extracted from the wound and the detection of released immunological mediators in skin extracts and in the skin culture media. We found that Cipro-foils effectively treated the infection with both PAO1 and MRSA. Other than PAO1, MRSA had no lytic activity toward skin proteins. MRSA infections increased cytokines’ expression and release. Interestingly, treatment with Cipro-foils could partially counteract these effects.

International audience; Drug permeation across the cornea remains a major challenge due to its unique and complex anatomy and physiology. Static barriers such as the different layers of the cornea, as well as dynamic aspects such as the constant renewal of the tear film and the presence of the mucin layer together with efflux pumps, all present unique challenges for effective ophthalmic drug delivery. To overcome some of the current ophthalmic drug limitations, the identification and testing of novel drug formulations such as liposomes, nanoemulsions, and nanoparticles began to be considered and widely explored. In the early stages of corneal drug development reliable in vitro and ex vivo alternatives, are required, to be in line with the principles of the 3Rs (Replacement, Reduction, and Refinement), with such methods being in addition faster and more ethical alternatives to in vivo studies. The ocular field remains limited to a handful of predictive models for ophthalmic drug permeation. In vitro cell culture models are increasingly used when it comes to transcorneal permeation studies. Ex vivo models using excised animal tissue such as porcine eyes are the model of choice to study corneal permeation and promising advancements have been reported over the years. Interspecies characteristics must be considered in detail when using such models. This review updates the current knowledge about in vitro and ex vivo corneal permeability models and evaluates their advantages and limitations.

Considering the potential of nanostructured titanium dioxide layers as drug delivery systems, it is advisable to indicate the possibility of creating a functional drug delivery system based on anodic TiO2 for celecoxib as an alternative anti-inflammatory drug and its inclusion complex with β-cyclodextrin. First, the optimal composition of celecoxib—β-cyclodextrin complexes was synthesized and determined. The effectiveness of the complexation was quantified using isothermal titration calorimetry (ITC), differential scanning calorimetry (DSC), infrared spectroscopy (FT-IR) nuclear magnetic resonance (1H NMR), and scanning electron microscopy (SEM). Then, nanostructured titanium dioxide layers (TiO2) were synthesized using the electrochemical oxidation technique. The TiO2 layers with pore diameters of 60 nm and layer thickness of 1.60 µm were used as drug delivery systems. The samples were modified with pure celecoxib and the β-cyclodextrin-celecoxib complex. The release profiles shown effective drug release from such layers during 24 h. After the initial burst release, the drug was continuously released from the pores. The presented results confirm that the use of nanostructured TiO2 as a drug delivery system can be effectively used in more complicated systems composed of β-cyclodextrin—celecoxib complexes, making such drugs available for pain treatment, e.g., for orthopedic surgeries.

Curcumin (Cur) is a beneficial ingredient with numerous bioactivities. However, due to its low solubility and poor bioavailability, its therapeutic application is limited. In this work, we prepared poly-N-isopropylacrylamide p(NIPAm) and polyallylamine p(Am)-based nanogel (p(NIPAm-co-Am)) NG for a dual pH- and temperature-sensitive copolymer system for drug delivery application. In this copolymer system, the p(NIPAm) segment was incorporated to introduce thermoresponsive behavior and the p(Am) segment was incorporated to introduce drug binding sites (amine groups) in the resulting (p(NIPAm-co-Am)) NG system. Various instrumental characterizations including 1H nuclear magnetic resonance (1H NMR) spectroscopy, Fourier transform infrared (FT-IR) analysis, scanning electron microscopy (SEM), zeta potential, and particle size analysis were performed to confirm the copolymer synthesis. Curcumin (Cur), an anticancer bioactive substance, was employed to assess the in vitro drug loading and release performance of the resulting copolymer nanogels system at varied pH levels (pH 7.2, 6.5, and 4.0) and temperatures (25 °C, 37 °C, and 42 °C). The cytocompatibility of the p(NIPAm-co-Am) NG sample was also tested on MDA-MB-231 cells at various sample concentrations. All the study results indicate that the p(NIPAm-co-Am) NG produced might be effective for drug loading and release under pH and temperature dual-stimuli conditions. As a result, the p(NIPAm-co-Am) NG system has the potential to be beneficial in the use of drug delivery applications in cancer therapy.