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The most popular and patient-friendly method of drug administration is often thought to be the oral route of administration. Compared to conventional release formulations, advancements in formulation technology, including modified release dosage forms or sustained release oral dosage forms, have been extensively accepted. A sustained release dosage form provides a prolonged release of the drug over an extended period, thereby giving better patient compliance and enhanced bioavailability. Sustain release systems are considered a wiser approach for drugs with short half-lives requiring repeated dosing. Sustained release drug delivery has a range of advantages over conventional dosage forms, including increased patient compliance due to less frequent drug administration, significantly reduced steady state drug level fluctuations, maximum drug utilization, the increased safety margin of potent drugs, lower healthcare costs due to improved therapy, and shorter treatment times. The present review focuses on design, fabrication, and various factors that influence the performance of sustained-release dosage forms.

Background: Extracellular vesicles (EVs) are a heterogeneous family of small vesicles released by donor cells and absorbed by recipient cells, which represent important mediators with fundamental roles in both physiological and pathological conditions. EVs are present in a large variety of biological fluids and have a great diagnostic and prognostic value. They have gained the interest of the scientific community due to their extreme versatility. In fact, they allow us to hypothesize new therapeutic strategies since, in addition to being cell signal mediators, they play an important role as biomarkers, drug vehicles, and potential new therapeutic agents. They are also involved in immunoregulation, have the ability to transmit resistance to a drug from one cell to a more sensitive one, and can act as drug delivery systems. Objective: The main reciprocal interactions between EVs and immunosuppressive drugs will be presented. Results: The known interactions between EVs and immunosuppressive drugs, in particular cyclosporin, glucocorticoids, rapamycin, methotrexate, cyclophosphamide, eculizumab, infliximab, certolizumab, etanercept, glatiramer acetate, and fingolimod are presented. Conclusion: This review provides relevant information on the links between EVs and immunosuppressive drugs with a focus on EVs' role as tools to assess the effects of immunosuppressants, suggesting innovative properties and new possible therapeutic uses.

A novel approach for the long-term medical treatment of the inner ear is the diffusion of drugs through the round window membrane from a patient-individualized, drug-eluting implant, which is inserted in the middle ear. In this study, drug-loaded (10 wt% Dexamethasone) guinea pig round window niche implants (GP-RNIs, ~1.30 mm × 0.95 mm × 0.60 mm) were manufactured with high precision via micro injection molding (µIM, Tmold = 160 °C, crosslinking time of 120 s). Each implant has a handle (~3.00 mm × 1.00 mm × 0.30 mm) that can be used to hold the implant. A medical-grade silicone elastomer was used as implant material. Molds for µIM were 3D printed from a commercially available resin (TG = 84 °C) via a high-resolution DLP process (xy resolution of 32 µm, z resolution of 10 µm, 3D printing time of about 6 h). Drug release, biocompatibility, and bioefficacy of the GP-RNIs were investigated in vitro. GP-RNIs could be successfully produced. The wear of the molds due to thermal stress was observed. However, the molds are suitable for single use in the µIM process. About 10% of the drug load (8.2 ± 0.6 µg) was released after 6 weeks (medium: isotonic saline). The implants showed high biocompatibility over 28 days (lowest cell viability ~80%). Moreover, we found anti-inflammatory effects over 28 days in a TNF-α-reduction test. These results are promising for the development of long-term drug-releasing implants for human inner ear therapy.

Kersen (Muntingia calabura L.) contains flavonoids that have the potential as antioxidants. However, its hydrophilic characteristics cause poor penetration so that its bioavailability is low. Research had been carried out on the preparation of ethanol extract of cherry leaves in ethosomal vesicle carriers. This study aimed to obtain the optimal phytosome suspension formula. Methods: Sample extraction was carried out by maceration method using ethanol as a solvent and was delipidated was by liquid-liquid method with n-hexane. The characterization of the extract included organoleptic, water-soluble extract content, ethanol soluble extract content, water content, ash content, acid insoluble ash content, and residual solvent. flavonoid contents were carried out by the TLC method and antioxidant activity was determined using DPPH method. Phytosome preparation was prepared by solvent evaporation and thin film hidration with ratio of extract and phosphatidylcholine 1:1 with concentration of 0.5% (A); 1% (B); and 1.5% (C). The characterization included observing morphology of vesicles using optical microscope, determining the size distribution of vesicles using PSA, and calculating the sorption efficiency using a spectrophotometer at max 281 nm. Results: The characteristics of extract were dark green; thick; distinctive aroma; ethanol soluble content were 70.91%; water soluble content were 32.5%; water content were 1.19%; ash content were 1.25%; acid insoluble ash content were 0.49%; and the remaining solvent was 0. The identification of flavonoids showed positive results. The extract has flavonoids and strong antioxidant activity with 62.71 g/mL for IC50. The shape is single layer large vesicle (LUV), diameter was 445.7 nm (A); 420.7 nm (B); and 419.6 nm (C). Vesicle entrapment efficiency was 5.83% (A); 47.575% (B); and 68.81% (C). It can be concluded that the optimal phytosome suspension formula is C with 1.5% phosphatidylcholine and 1.5% of extract.

BACKGROUND Liver cancer is the fourth most significant cause of cancer-related death. Lack of early diagnosis strategy and a scarcity of efficient therapy constitute the main reasons for its lethality. Exosomes, which contain various bioactive molecules, are characterized by high biocompatibility, low immunogenicity, and high transport efficiency. As a result, exosomes have become a research hotspot and present significant potential for cancer diagnosis biomarkers, biotherapeutics, therapy targets, drug carriers and therapeutic agents. AIM To explore the potential of exosomes in the diagnosis and treatment of liver cancer. METHODS We conducted a systematic literature search via PubMed and Web of Science. The following keywords were used: "exosomal biomarkers", "exosomal therapy", "exosomal therapy", and "liver cancer" or "HCC". The duplicate data were deleted by EndNote software. Literature search focused on full-texts and references of each article were carefully checked. One author (Xiao-Cui Wei) screened the literature that met the following inclusion criteria: (1) Detection of exosomes or their contents in clinical samples (body fluid or tissue); or (2) Exosomes served as drug carriers or therapeutic factors. Two authors (Xiao-Cui Wei and Li-Juan Liu) independently reviewed all retained literature and analyzed the information. RESULTS A total of 1295 studies were identified using the systematic literature search. Of these, 835 duplicate studies were removed. A further 402 irrelevant studies were excluded due to being irrelevant, including other diseases, review articles, the literature containing neither clinical samples nor animal experiments, exosome-independent studies, methods for detecting exosomes, or articles in Chinese. Finally, 58 published papers were retained and analyzed in the study. It showed a list of potential exosomal biomarkers that were upregulated in the blood samples of patients with liver cancer. Those downregulated in exosomes might serve as possible biotherapeutics. Some exosomes derived from cells in vitro were used for cytology or animal experiments to explore the mechanism of these exosome contents in disease. These contents might serve as potential targets for liver cancer. Additionally, we also discussed that exosomes serve as drug carriers or therapeutic factors. CONCLUSION Exosomes might serve as potential biomarkers or therapeutic biotargets in liver cancer and have the potential to act as drug carriers and self-treatment factors for liver cancer patients.

Hyaluronic acid (HA)-coated biodegradable polymeric micelles were developed as nanoparticulate vaccine delivery systems to establish an effective nasal vaccine. We previously reported HA-coated micelles prepared by forming a polyion complex (PIC) of poly(L-lysine)-b-polylactide (PLys⁺-b-PLA) micelles and HA. The HA-coated micelles exhibited specific accumulation in HA receptor-expressing cells and extremely high colloidal stability under diluted blood conditions. In this study, a model antigen, ovalbumin (OVA), and an adjuvant oligonucleotide containing the CG motif (CpG-DNA) were efficiently loaded in HA-coated micelles via electrostatic interactions. HA-coated micelles delivered OVA and CpG-DNA in mouse bone marrow-derived dendritic cells (BMDCs) and resulted in upregulation of mRNA encoding IFN-γ and IL-4 in BMDCs. In addition, HA-coated micelles enhanced the expression of the major histocompatibility complex (MHC) class II on BMDCs. We investigated the immune response of HA-coated micelles following intranasal administration. HA-coated micelles induced higher OVA-specific IgG in the blood and OVA-specific IgA in the nasal wash than control (carboxymethyl dextran-coated) micelles. These results suggest that HA-coated micelles efficiently deliver antigens and adjuvants to mucosal-resident immune cells. Therefore, HA-coated micelles are promising platforms for developing nasal vaccines against infectious diseases., This work was financially supported in part by the Private University Research Branding Project: Matching Fund Subsidy from the Ministry of Education, Culture, Sports, Science, and Technology (MEXT) Japan (2016–2020), Grants-in-Aid for Scientific Research (20H00670) from the Japan Society for the Promotion of Science (JSPS), and Kansai University Contingency Fund for Education and Research Outlay (2020)., 2020年度関西大学教育研究緊急支援経費 研究課題「高分子ミセルを用いた対コロナウイルス経鼻型ワクチンの開発」

Ischemic stroke (IS) is one of the leading causes of death and disability resulting in inevitable burden globally. Ischemic injury initiates cascade of pathological events comprising energy dwindling, failure of ionic gradients, failure of blood brain barrier (BBB), vasogenic edema, calcium over accumulation, excitotoxicity, increased oxidative stress, mitochondrial dysfunction, inflammation and eventually cell death. In spite of such complexity of the disease, the only treatment approved by US Food and Drug Administration (FDA) is tissue plasminogen activator (t-PA). This therapy overcome blood deficiency in the brain along with side effects of reperfusion which are responsible for considerable tissue injury. Therefore, there is urgent need of novel therapeutic perspectives that can protect the integrity of BBB and salvageable brain tissue. Advancement in nanomedicine is empowering new approaches that are potent to improve the understanding and treatment of the IS. Herein, we focus nanomaterial mediated drug delivery systems (DDSs) and their role to bypass and cross BBB especially via intranasal drug delivery. The various nanocarriers used in DDSs are also discussed. In a nut shell, the objective is to provide an overview of use of nanomedicine in the diagnosis and treatment of IS to facilitate the research from benchtop to bedside.

Corneal neovascularization is a serious corneal pathological change caused by various factors. The drug delivery system is of great significance for the effective treatment of corneal neovascularization. Herein, we developed and characterized a monolith/hydrogel composite as the triamcinolone acetonide (TA) carrier for curing corneal neovascularization. The composite was prepared by photo-initiated free radical polymerization of multi-methacrylate substituted dodecamine organic molecular cage and post-modified by the sequential photo-initiated free radical polymerization of acrylated gelatin. The globular morphology and structural property of as-prepared composites were evaluated by scanning electron microscopy, Fourier-transform infrared spectroscopy and solid-state cross polarization magic angle spinning carbon-13 nuclear magnetic resonance. Then swelling ratio and the TA loading capacity were investigated then. Compared with gelatin hydrogel, the composites exhibited a decreased swelling ratio and an improved loading capacity. With good biocompatibility, the composite can sustainedly release TA for up to 28 days, and effectively inhibit corneal neovascularization with an alkali burn-induced corneal neovascularization model. Additionally, tandem mass tags-labeled quantitative proteomics were performed to identify differentially expressed proteins between vascularized and devascularized corneas. The Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed that the inhibition process could be primarily linked to the fibrinolytic system. These results demonstrated the potential of monolith/hydrogel composites as delivery systems in the therapy for biomedical diseases.

Gastrointestinal (GI) malignancies, a series of malignant conditions originating from the digestive system, include gastric cancer, hepatocellular carcinoma, pancreatic cancer, and colorectal cancer. GI cancers have been regarded as the leading cancer-related cause of death in recent years. Therefore, it is essential to develop effective treatment strategies for GI malignancies. Mesenchymal stem cells (MSCs), a type of distinct non-hematopoietic stem cells and an important component of the tumor microenvironment, play important roles in regulating GI cancer development and progression through multiple mechanisms, such as secreting cytokines and direct interactions. Currently, studies are focusing on the anti-cancer effect of MSCs on GI malignancies. However, the effects and functional mechanisms of MSC-derived exosomes on GI cancer are less studied. MSC-derived exosomes can regulate GI tumor growth, drug response, metastasis, and invasion through transplanting proteins and miRNA to tumor cells to activate the specific signal pathway. Besides, the MSC-derived exosomes are also seen as an important drug delivery system and have shown potential in anti-cancer treatment. This study aims to summarize the effect and biological functions of MSC-derived exosomes on the development of GI cancers and discuss their possible clinical applications for the treatment of GI malignancies.

Bone tumors are tumors that occur in the bone or its accessory tissues, including primary tumors and metastatic tumors. The main mechanism of bisphosphonate is to inhibit the resorption of destructive bone, inhibit the activity of osteoclasts and reduce the concentration of blood calcium. Therefore, bisphosphonates can be used for malignant hypercalcaemia, pain caused by osteolytic bone metastasis, prevention of osteolytic bone metastasis, multiple myeloma osteopathy, improving radiosensitivity and so on. However, the traditional administration of bisphosphonates can cause a series of adverse reactions. To overcome this disadvantage, it is necessary to develop novel methods to improve the delivery of bisphosphonates. In this paper, the latest research progress of new and improved bisphosphonate drug delivery methods in the treatment of bone tumors is reviewed. At present, the main design idea is to connect bisphosphonate nanoparticles, liposomes, microspheres, microcapsules, couplings, prodrugs and bone tissue engineering to targeted anti-tumors systems, and positive progress has been made in in vitro and animal experiments. However, its safety and effectiveness in human body still need to be verified by more studies.

Probiotics have demonstrated their high potential to treat and/or prevent various diseases including neurodegenerative disorders, cancers, cardiovascular diseases, and inflammatory diseases. Probiotics are also effective against multidrug-resistant pathogens and help maintain a balanced gut microbiota ecosystem. Accordingly, the global market of probiotics is growing rapidly, and research efforts to develop probiotics into therapeutic adjuvants are gaining momentum. However, because probiotics are living microorganisms, many biological and biopharmaceutical barriers limit their clinical application. Probiotics may lose their activity in the harsh gastric conditions of the stomach or in the presence of bile salts. Moreover, they easily lose their viability under thermal or oxidative stress during their preparation and storage. Therefore, stable formulations of probiotics are required to overcome the various physicochemical, biopharmaceutical, and biological barriers and to maximize their therapeutic effectiveness and clinical applicability. This review provides an overview of the pharmaceutical applications of probiotics and covers recent formulation approaches to optimize the delivery of probiotics with particular emphasis on various dosage forms and formulation technologies.

In present study, we describe a promising radiolabeled drug delivery system for Methotrexate (MTX), an anticancer drug used in the treatment of breast cancer. Uniform and re-dispersible MSN were synthesized with a particle size of as 42.55 +/- 1.45 nm. Then, MTX was loaded into the surface modified MSN with DTPA over 95% loading capacity. Subsequently, MTX loaded MSN carrier system was radiolabeled with Tc-99 m (Tc-99m-MTX-MSN) with 92.20 +/- 0.8% radiolabeling yield. Furthermore, in vitro evaluation on estrogen positive (ER +) MCF7 and estrogen negative (ER-) A549 cells lines were performed for determining apoptotic and cytotoxic effects of MTX-MSN, and incorporation behavior of Tc-99m-MTX-MSN. Drug loaded MSN particles were exhibit higher uptake in MCF7 cells than A549 cells., Ege University Scientific Research Projects Coordination Unit [2017NBE006], The authors gratefully acknowledge the support by Ege University Scientific Research Projects Coordination Unit (Funding Number: 2017NBE006).

Recurrent aphthous stomatitis (RAS) is a disease marked by painful oral lesions on the buccal and labial mucosa or tongue. Drug delivery systems (DDS) for RAS include topical forms that manage wound healing, cover the ulcer, and relieve the associated pain. DDS targeting the oral mucosa face a major challenge, especially the short residence times in the mouth due to the effect of “saliva wash-out”, which continually removes the drug. The objective of this review is to study the development of preparation forms and delivery systems of various types and preparations that have been used for RAS management from 1965 until February 2020. There are 20 types of DDS for RAS which were discussed in 62 articles. The preparations were classified into 4 preparation forms: liquid, semi-solid, solid, and miscellaneous. In addition, the ultimate DDS for RAS preparations is the semi-solid forms (41.94%), which include 5 types of DDS are gel, paste, patch, cream, and ointment. This preparation was developed into new preparation form (11.29%), such as adhesive alginates, dentifrice, OraDisc, membranes, bioresorbable plates, pellicles, and gelosomes. Generally, the mucosal drug delivery system is the method of choice in RAS treatment because the ulcer is commonly located in the oral mucosa. In conclusion, these preparations are designed to improve drug delivery and drug activity for the treatment of RAS ulcers. Moreover, almost all of these DDS are topical preparations that use various types of mucoadhesive polymers to increase both residence time in the oral mucosa and pain relief in RAS treatment., Graphical Abstract

NLCs have provoked the incessant impulsion for the development of safe and valuable drug delivery systems owing to their exceptional physicochemical and then biocompatible characteristics. Throughout the earlier period, a lot of studies recounting NLCs based formulations have been noticeably increased. They are binary system which contains both solid and liquid lipids aiming to produce less ordered lipidic core. Their constituents particularly influence the physicochemical properties and effectiveness of the final product. NLCs can be fabricated by different techniques which are classified according to consumed energy. More utilization NLCs is essential due to overcome barriers surrounded by the technological procedure of lipid-based nanocarriers' formulation and increased information of the core mechanisms of their transport via various routes of administration. They can be used in different applications and by different routes such as oral, cutaneous, ocular and pulmonary. This review article seeks to present an overview on the existing situation of the art of NLCs for future clinics through exposition of their applications which shall foster their lucid use. The reported records evidently demonstrate the promise of NLCs for innovate therapeutic applications in the future.

The complex drug delivery barrier in the eye reduces the bioavailability of many drugs, resulting in poor therapeutic effects. It is necessary to investigate new drugs through appropriate delivery routes and vehicles. Nanotechnology has utilized various nano-carriers to develop potential ocular drug delivery techniques that interact with the ocular mucosa, prolong the retention time of drugs in the eye, and increase permeability. Additionally, nano-carriers such as liposomes, nanoparticles, nano-suspensions, nano-micelles, and nano-emulsions have grown in popularity as an effective theranostic application to combat different microbial superbugs. In this review, we summarize the nano-carrier based drug delivery system developments over the last decade, particularly review the biology, methodology, approaches, and clinical applications of nano-carrier based drug delivery system in the field of ocular therapeutics. Furthermore, this review addresses upcoming challenges, and provides an outlook on potential future trends of nano-carrier-based drug delivery approaches in ophthalmology, and hopes to eventually provide successful applications for treating ocular diseases.

Glioblastoma (GBM) is the most common malignant neoplasm in adults among all CNS gliomas, with the 5-year survival rate being as low as 5%. Among nanocarriers, liposomal nanoformulations are considered as a promising tool for precise drug delivery. The herein presented study demonstrates the possibility of encapsulating four selected natural compounds (curcumin, bisdemethoxycurcumin, acteoside, and orientin) and their mixtures in cationic liposomal nanoformulation composed of two lipid types (DOTAP:POPC). In order to determine the physicochemical properties of the new drug carriers, specific measurements, including particle size, Zeta Potential, and PDI index, were applied. In addition, NMR and EPR studies were carried out for a more in-depth characterization of nanoparticles. Within biological research, the prepared formulations were evaluated on T98G and U-138 MG glioblastoma cell lines in vitro, as well as on a non-cancerous human lung fibroblast cell line (MRC-5) using the MTT test to determine their potential as anticancer agents. The highest activity was exhibited by liposome-entrapped acteoside towards the T98G cell line with IC50 equal 2.9 ± 0.9 µM after 24 hours of incubation. Noteworthy, curcumin and orientin mixture in liposomal formulation exhibited a synergistic effect against GBM. Moreover, the impact on the expression of apoptosis-associated proteins (p53 and Caspase-3) of acteoside as well as curcumin and orientin mixture, as the most potent agents, was assessed, showing nearly 40% increase as compared to control U-138 MG and T98G cells. It should be emphasized that a new and alternative method of extrusion of the studied liposomes was developed.

Extracellular vesicles (EVs) represent a diverse class of lipid bilayer membrane vesicles released by both animal and plant cells. These ubiquitous vesicles are involved in intercellular communication and transport of various biological cargos, including proteins, lipids, and nucleic acids. In recent years, interest in plant-derived EVs has increased tremendously, as they serve as a scalable and sustainable alternative to EVs derived from mammalian sources. In vitro and in vivo findings have demonstrated that these plant-derived vesicles (PDVs) possess intrinsic therapeutic activities that can potentially treat diseases and improve human health. In addition, PDVs can also act as efficient and biocompatible drug carriers. While preclinical studies have shown promising results, there are still several challenges and knowledge gaps that have to be addressed for the successful translation of PDVs into clinical applications, especially in view of the lack of standardised protocols for material handling and PDV isolation from various plant sources. This review provides the readers with a quick overview of the current understanding and research on PDVs, critically analysing the current challenges and highlighting the immense potential of PDVs as a novel class of therapeutics to treat human diseases. It is expected that this work will guide scientists to address the knowledge gaps currently associated with PDVs and promote new advances in plant-based therapeutic solutions.

Acknowledgements The authors thank the Fundaç˜ao para a Ciˆencia e Tecnologia (FCT), Portugal for the financial support and Centro 2020 through the following projects: UIDB/04138/2020 and UIDP/04138/2020 (iMed. ULisboa), UIDB/05608/2020 and UIDP/05608/2020 (H&TRC), UIDP/ 04044/2020, PAMI - ROTEIRO/0328/2013 (N◦ 022158) and MATIS (CENTRO-01-0145-FEDER-000014 - 3362), L. Gonçalves Principal Researcher grant (CEECIND/03143/2017). Finally, the authors would like to thank VOCO GmbH (Cuxhaven, Germany) for the donation of the Ufi Gel Hard and Prof Alice Nogueira Alves for graphical advice., The high recurrence rate of common denture stomatitis after antifungal treatment is still concerning. This condition is caused by low patient compliance and incomplete local elimination of the main etiological factor — Candida albicans, often associated with other microorganisms, such as Streptococcus species. Impregnating denture materials with antimicrobials for local delivery is a strategy that can overcome the side effects and improve the efficacy of conventional treatments (topical and/or systemic). In this work, we describe the development of three hard autopolymerizing reline acrylic resins (Kooliner, Ufi Gel Hard, and Probase Cold) loaded with different percentages of chlorhexidine (CHX). The novel formulations were characterized based on their antimicrobial activity, mechanical, morphological and surface properties, in-vitro drug release profiles, and cytotoxicity. The addition of CHX in all resins did not change their chemical and mechanical structure. Among all the tested formulations, Probase Cold loaded with 5 wt% CHX showed the most promising results in terms of antimicrobial activity and lack of serious detrimental mechanical, morphological, surface, and biological properties., Fundação para a Ciência e Tecnologia (FCT), Portugal, Centro 2020 through the following projects: UIDB/04138/2020 and UIDP/04138/2020 (iMed.ULisboa), UIDB/05608/2020 and UIDP/05608/2020 (H&TRC), UIDP/04044/2020, PAMI - ROTEIRO/0328/2013 (N° 022158), MATIS (CENTRO-01-0145-FEDER-000014 - 3362), Grant (CEECIND/03143/2017)

Nowadays, modern pharmaceutical investigations are directed toward the design and production of drug delivery systems for achieving prolonged and controlled drug delivery. In this respect, the use of interpenetrating polymer networks (IPNs) is an opportunity in the preparation of polymer drug delivery systems with desired characteristics. This paper describes the synthesis and characterization of novel poly(2-(dimethylamino) ethyl methacrylate) (PDMAEMA) and polyacrylamide (PAAm)-based IPNs with different compositions and their application as diclofenac sodium delivery systems. The prepared IPNs were shown to possess phase-separated structures at the nano level, as revealed by SEM and TM-DSC. The IPNs’ composition was shown to determine the swelling behavior of these novel materials, and the inclusion of the charged IPN component (PDMAEMA) has changed the water molecules type diffusion from Fickian to non-Fickian, as revealed by the swelling kinetics study. Loading efficiency of diclofenac sodium and diclofenac sodium content in the polymer network was evaluated, and in vitro drug release experiments were carried out in order to estimate the ability of the obtained IPNs to control the release of the water-soluble drug.

Hop (Humulus lupulus L.) is a plant used as an ingredient in beer or employed for its anti-inflammatory properties. The cultivation of hops is currently dedicated to the brewing industry, where mainly female flowers are used, whereas aerial parts, such as leaves, are considered coproducts. Osteoarthritis is the most common musculoskeletal disease associated with low-grade cartilage inflammation. Liposomes have been shown to be promising systems for drug delivery to cartilage cells, called chondrocytes. The aim of our work was to vectorize hop extract valorized from coproducts as a therapeutic agent to alleviate inflammation in human chondrocytes in vitro. Liquid chromatography allowed the identification of oxidized bitter acids in a methanolic extract obtained from the leaves of Cascade hops. The extract was encapsulated in rapeseed lecithin nanoliposomes, and the physicochemical properties of empty or loaded nanoliposomes exhibited no difference. Increasing concentrations of the hop extract alone, empty nanoliposomes, and loaded nanoliposomes were tested on human chondrocytes to assess biocompatibility. The appropriate conditions were applied to chondrocytes stimulated with interleukin-1β to evaluate their effect on inflammation. The results reveal that encapsulation potentiates the hop extract anti-inflammatory effect and that it might be able to improve joint inflammation in osteoarthritis. Furthermore, these results also show that a “zero waste” chain is something that can be achieved in hop cultivation.

The research for alternative administration methods for anticancer drugs, towards enhanced effectiveness and selectivity, represents a major challenge for the scientific community. In the last decade, polymeric nanostructured delivery systems represented a promising alternative to conventional drug administration since they ensure secure transport to the selected target, providing active compounds protection against elimination, while minimizing drug toxicity to non-target cells. In the present research, poly(glycerol sebacate), a biocompatible polymer, was synthesized and then nanostructured to allow curcumin encapsulation, a naturally occurring polyphenolic phytochemical isolated from the powdered rhizome of Curcuma longa L. Curcumin was selected as an anticancer agent in virtue of its strong chemotherapeutic activity against different cancer types combined with good cytocompatibility within healthy cells. Despite its strong and fascinating biological activity, its possible exploitation as a novel chemotherapeutic has been hampered by its low water solubility, which results in poor absorption and low bioavailability upon oral administration. Hence, its encapsulation within nanoparticles may overcome such issues. Nanoparticles obtained through nanoprecipitation, an easy and scalable technique, were characterized in terms of size and stability over time using dynamic light scattering and transmission electron microscopy, confirming their nanosized dimensions and spherical shape. Finally, biological investigation demonstrated an enhanced cytotoxic effect of curcumin-loaded PGS-NPs on human cervical cancer cells compared to free curcumin.

Three-dimensional printing is a technology that prints the products layer-by-layer, in which materials are deposited according to the digital model designed by computer aided design (CAD) software. This technology has competitive advantages regarding product design complexity, product personalization, and on-demand manufacturing. The emergence of 3D technology provides innovative strategies and new ways to develop novel drug delivery systems. This review summarizes the application of 3D printing technologies in the pharmaceutical field, with an emphasis on the advantages of 3D printing technologies for achieving rapid drug delivery, personalized drug delivery, compound drug delivery and customized drug delivery. In addition, this article illustrates the limitations and challenges of 3D printing technologies in the field of pharmaceutical formulation development.

Drug delivery devices are promising tools in the pharmaceutical field, as they are able to maximize the therapeutic effects of the delivered drug while minimizing the undesired side effects. In the past years, electrospun nanofibers attracted rising attention due to their unique features, like biocompatibility and broad flexibility. Incorporation of active principles in nanofibrous meshes proved to be an efficient method for in situ delivery of a wide range of drugs, expanding the possibility and applicability of those devices. In this review, the principle of electrospinning and different fields of applications are treated to give an overview of the recent literature, underlining the easy tuning and endless combination of this technique, that in the future could be the new frontier of personalized medicine.

Senile plaques composed of amyloid β (Aβ) fibrils are considered the leading cause of Alzheimer’s disease (AD). Molecules with the ability to inhibit Aβ aggregation and/or promote Aβ clearance are thus a promising approach for AD therapy. Our group recently demonstrated that gallic acid (GA) has strong anti-amyloidogenic properties. In this study, stealth liposomes were prepared for the delivery of GA for AD therapy. The liposomes were functionalized with transferrin (Tf) to direct them to the brain, since Tf receptors are overexpressed in the endothelial cells of the blood–brain barrier. GA-loaded Tf-functionalized liposomes showed mean diameters of 130 nm, low polydispersity index values, and neutral zeta potential. Moreover, the produced nanocarriers promoted the sustained release of GA over 5 days and are physically stable for 1 month under storage conditions. Furthermore, GA-loaded Tf-functionalized liposomes showed a strong ability to interact with Aβ1-42 monomers, slowing down the Aβ monomer-to-oligomer and oligomer-to-fibril transitions and decreasing the number of fibrils formed by 56%. In addition, the NPs disaggregated approximately 30% of preformed Aβ fibrils. The presented results suggest that Tf-functionalized liposomes could be a viable platform for the brain delivery of GA for AD therapy. Studies with animal models of AD will be valuable for validating the therapeutic efficacy of this novel liposomal formulation.

Polymeric drug delivery systems have been studied in the last 20 years and have achieved great developments. Polymeric matrix type delivery systems (also called “one-block system” or “monolithic system”) are essentially a mixture of drug and polymer homogeneously distributed throughout the device. This new generation of implants has shown promising capabilities to overcome the inherent problems of conventional implants and therapies, presenting minimal side effects and making clinical treatments more efficient. The polymeric drug delivery systems are proving themselves to be safe regarding the drug content and prolonged release, while also very effective in improving the daily life and life expectancy of patients. Within this context, this review is aimed at highlighting the main characteristics of the matrix type polymeric drug delivery systems.

Diclofenac sodium tablets were successfully prepared via hot-melt extrusion (HME) and fused deposition modeling (FDM), using different molecular-weight (Mw) grades of hydroxyethyl cellulose (HEC) as the main excipient. Hydroxypropyl cellulose (HPC) was added to facilitate HME and to produce drug-loaded, uniform filaments. The effect of the HEC grades (90–1000 kDa) on the processability of HME and FDM was assessed. Mechanical properties of the filaments were evaluated using the three-point bend (3PB) test. Breaking stress and distance were set in relation to the filament feedability to identify printer-specific thresholds that enable proper feeding. The study demonstrated that despite the HEC grade used, all formulations were at least printable. However, only the HEC L formulation was feedable, showing the highest breaking stress (29.40 ± 1.52 MPa) and distance (1.54 ± 0.08 mm). Tablet drug release showed that the release was Mw dependent up to a certain HEC Mw limit (720 kDa). Overall, the release was driven by anomalous transport due to drug diffusion and polymer erosion. The results indicate that despite being underused in FDM, HEC is a suitable main excipient for 3D-printed dosage forms. More research on underutilized polymers in FDM should be encouraged to increase the limited availability.

Lipid nanoparticles based on lecithin are an interesting part of drug delivery systems. However, the stability of lecithin nano-lipids is problematic due to the degradation of lecithin, causing a decrease in pH. In this study, the modification of the conventional nano-lipid-based soybean lecithin was demonstrated. Ginger-oil-derived Zingiber officinale was used along with lecithin, cholesterol and span 80 to fabricate nano-lipids (GL nano-lipids) using a thin-film method. TEM and a confocal microscope were used to elucidate GL nano-lipids’ liposome-like morphology. The average size of the resultant nano-lipid was 249.1 nm with monodistribution (PDI = 0.021). The ζ potential of GL nano-lipids was negative, similarly to as-prepared nano-lipid-based lecithin. GL nano-lipid were highly stable over 60 days of storage at room temperature in terms of size and ζ potential. A shift in pH value from alkaline to acid was detected in lecithin nano-lipids, while with the incorporation of ginger oil, the pH value of nano-lipid dispersion was around 7.0. Furthermore, due to the richness of shogaol-6 and other active compounds in ginger oil, the GL nano-lipid was endowed with intrinsic antibacterial activity. In addition, the sulforhodamine B (SRB) assay and live/dead imaging revealed the excellent biocompatibility of GL nano-lipids. Notably, GL nano-lipids were capable of carrying hydrophobic compounds such as curcumin and performed a pH-dependent release profile. A subsequent characterization showed their suitable potential for drug delivery systems.

Excessive postoperative scarring halts the effectiveness of glaucoma surgery and still remains a challenging problem. The purpose of this study was to develop a PLA-PEG-based drug delivery system with cyclosporine A or everolimus for wound healing modulation. Methods: PLA-PEG implants saturation with cyclosporine A or everolimus as well as their further in vitro release were analyzed. Anti-proliferative activity and cytotoxicity of the immunosuppressants were studied in vitro using human Tenon’s fibroblasts. Thirty-six rabbits underwent glaucoma filtration surgery with the application of sham implants or samples saturated with cyclosporine A or everolimus. The follow-up period was six months. A morphological study of the surgery area was also performed at seven days, one, and six months post-op. Results: PLA-PEG implants revealed a satisfactory ability to cumulate either cyclosporine A or everolimus. The most continuous period of cyclosporine A and everolimus desorption was 7 and 13 days, respectively. Immunosuppressants demonstrated marked anti-proliferative effect regarding human Tenon’s fibroblasts without signs of cytotoxicity at concentrations provided by the implants. Application of PLA-PEG implants saturated with immunosuppressants improved in vivo glaucoma surgery outcomes. Conclusions: Prolonged delivery of either cyclosporine A or everolimus by means of PLA-PEG implants represents a promising strategy of wound healing modulation in glaucoma filtration surgery.

Osteoarthritis (OA) is a degenerative and heterogeneous disease that affects all types of joint structures. Current clinical treatments are only symptomatic and do not manage the degenerative process in animals or humans. One of the new orthobiological treatment strategies being developed to treat OA is the use of drug delivery systems (DDS) to release bioactive molecules over a long period of time directly into the joint to limit inflammation, control pain, and reduce cartilage degradation. Two vasoactive peptides, endothelin-1 and bradykinin, play important roles in OA pathogenesis. In this study, we investigated the effects of two functionalized nanogels as DDS. We assessed the effect of chitosan functionalized with a type A endothelin receptor antagonist (BQ-123-CHI) and/or hyaluronic acid functionalized with a type B1 bradykinin receptor antagonist (R-954-HA). The biocompatibility of these nanogels, alone or in combination, was first validated on equine articular chondrocytes cultured under different oxic conditions. Further, in an OA equine organoid model via induction with interleukin-1 beta (IL-1β), a combination of BQ-123-CHI and R-954-HA (BR5) triggered the greatest decrease in inflammatory and catabolic markers. In basal and OA conditions, BQ-123-CHI alone or in equimolar combinations with R-954-HA had weak pro-anabolic effects on collagens synthesis. These new nanogels, as part of a composite DDS, show promising attributes for treating OA.

An immune response for a nasal ovalbumin (OVA) powder formulation with an applied nasal delivery platform technology, consisting of a powdery nasal carrier and a device, was evaluated in monkeys with similar upper respiratory tracts and immune systems to those of humans, in order to assess the applicability to a vaccine antigen. Nasal distribution and retention studies using a 3D nasal cavity model and manganese-enhanced MRI were conducted by administering nasal dye and manganese powder formulations with the applied technology. Systemic and mucosal immune responses for the nasal OVA powder formulation were evaluated by determining serum IgG and nasal wash IgA antibody titers. The nasal dye and manganese powder formulations showed wider distribution and longer retention time than did a nasal liquid formulation. The nasal OVA powder formulation also showed comparable and higher antigen-specific IgG antibody titer to an injection and nasal liquid formulation, respectively. Furthermore, antigen-specific IgA antibody response was detected only for the nasal OVA powder formulation. The present study suggests that the technology, originally designed for drug absorption, is promising for nasal vaccines, enabling both a mucosal immunity response as the first line of defense and systemic immunity response as a second line of defense against infection.

The effective colon drug delivery remains to be an international frontier research in inflammatory bowel disease (IBD) therapy. The exploration and research of nanocarrier-based nanomedicine with great potential brings new opportunities for IBD therapy and diagnoses. Functional nanocarriers with varying morphology and characteristics can not only effectively avoid the destruction of the complex gastrointestinal (GI) tract microenvironment but also endow drugs with target therapy and improved bioavailability, thus elevating therapeutic efficacy. In this review, we illustrated several challenges in IBD therapy, then emphasis on some latest research progress of nanoparticles based therapy of oral administration, rectal administration and parenteral administration, as well as IBD diagnoses. Finally, we described the future perspective of nanocarriers in the treatment and diagnoses of IBD.

Glycol chitosan (GC) is a chitosan (CH) derivative with improved water solubility with regards to CH which affords significant solubility advantages. In this study, microgels of GC as p(GC) were synthesized by a microemulsion technique at various crosslinking ratios e.g., 5%, 10%, 50%, 75%, and 150% based on the repeating unit of GC using divinyl sulfone (DVS) as a crosslinker. The prepared p(GC) microgels were tested for blood compatibility and it was found that p(GC) microgels at 1.0 mg/mL concentration possessed a 1.15 ± 0.1% hemolysis ratio and 89 ± 5% blood clotting index value confirming their hemocompatibility. In addition, p(GC) microgels were found biocompatible with 75.5 ± 5% cell viability against L929 fibroblasts even at a 2.0 mg/mL concentration. By loading and releasing tannic acid (TA) (a polyphenolic compound with high antioxidant activity) as an active agent, p(GC) microgels’ possible drug delivery device application was examined. The TA loading amount of p(GC) microgels was determined as 323.89 mg/g, and TA releases from TA loaded microgels (TA@p(GC)) were found to be linear within 9 h and a total amount of TA released was determined as 42.56 ± 2 mg/g within 57 h. According to the Trolox equivalent antioxidant capacity (TEAC) test, 400 µL of the sample added to the ABTS+ solution inhibited 68.5 ± 1.7% of the radicals. On the other hand, the total phenol content (FC) test revealed that 2000 μg/mL of TA@p(GC) microgels resulted in 27.5 ± 9.5 mg/mL GA eq antioxidant properties.

Bioactive calcium phosphate ceramics (CaPs) are one of the building components of the inorganic part of bones. Synthetic CaPs are frequently used as materials for filling bone defects in the form of pastes or composites; however, their porous structure allows modification with active substances and, thus, subsequent use as a drug carrier for the controlled release of active substances. In this study, four different ceramic powders were compared: commercial hydroxyapatite (HA), TCP, brushite, as well as HA obtained by wet precipitation methods. The ceramic powders were subjected to physicochemical analysis, including FTIR, XRD, and determination of Ca/P molar ratio or porosity. These techniques confirmed that the materials were phase-pure, and the molar ratios of calcium and phosphorus elements were in accordance with the literature. This confirmed the validity of the selected synthesis methods. CaPs were then modified with the antibiotic clindamycin. Drug release was determined on HPLC, and antimicrobial properties were tested against Staphylococcus aureus. The specific surface area of the ceramic has been demonstrated to be a factor in drug release efficiency.

In this study, we developed an efficient mRNA delivery vehicle by optimizing a lyophilization method for preserving human serum albumin-based nanobubbles (HSA-NBs), bypassing the need for artificial stabilizers. The morphology of the lyophilized material was verified using scanning electron microscopy, and the concentration, size, and mass of regenerated HSA-NBs were verified using flow cytometry, nanoparticle tracking analysis, and resonance mass measurements, and compared to those before lyophilization. The study also evaluated the response of HSA-NBs to 1 MHz ultrasound irradiation and their ultrasound (US) contrast effect. The functionality of the regenerated HSA-NBs was confirmed by an increased expression of intracellularly transferred Gluc mRNA, with increasing intensity of US irradiation. The results indicated that HSA-NBs retained their structural and functional integrity markedly, post-lyophilization. These findings support the potential of lyophilized HSA-NBs, as efficient imaging, and drug delivery systems for various medical applications.

The interest in the pharmacological applications of cannabinoids is largely increasing in a wide range of medical areas. Recently, research on its potential role in eye conditions, many of which are chronic and/or disabling and in need of new alternative treatments, has intensified. However, due to cannabinoids’ unfavorable physicochemical properties and adverse systemic effects, along with ocular biological barriers to local drug administration, drug delivery systems are needed. Hence, this review focused on the following: (i) identifying eye disease conditions potentially subject to treatment with cannabinoids and their pharmacological role, with emphasis on glaucoma, uveitis, diabetic retinopathy, keratitis and the prevention of Pseudomonas aeruginosa infections; (ii) reviewing the physicochemical properties of formulations that must be controlled and/or optimized for successful ocular administration; (iii) analyzing works evaluating cannabinoid-based formulations for ocular administration, with emphasis on results and limitations; and (iv) identifying alternative cannabinoid-based formulations that could potentially be useful for ocular administration strategies. Finally, an overview of the current advances and limitations in the field, the technological challenges to overcome and the prospective further developments, is provided. Programa Operacional Regional do Centro CENTRO-04- 3559-FSE-000162

A connection of a functional peptide with a cell-penetrating peptide (CPP) used a heterodimeric coiled-coil as a molecular zipper can improve the intracellular delivery and activity of the functional peptide. However, the chain length of the coiled coil required for functioning as the molecular zipper is unknown at present. To solve the problem, we prepared an autophagy-inducing peptide (AIP) that conjugates with the CPP via heterodimeric coiled-coils consisting of 1 to 4 repeating units (K/E zipper; AIP-Kn and En-CPP), and we investigated the optimum length of the K/E zipper for effective intracellular delivery and autophagy induction. Fluorescence spectroscopy showed that K/E zippers with n = 3 and 4 formed a stable 1:1 hybrid (AIP-K3/E3-CPP and AIP-K4/E4-CPP, respectively). Both AIP-K3 and AIP-K4 were successfully delivered into cells by the corresponding hybrid formation with K3-CPP and K4-CPP, respectively. Interestingly, autophagy was also induced by the K/E zippers with n = 3 and 4, more intensively by the former than by the latter. The peptides and K/E zippers used in this study did not show significant cytotoxicity. These results indicate that the effective induction of autophagy occurs via an exquisite balance of the association and dissociation of the K/E zipper in this system.

The short shelf life of platelet concentrates (PC) of up to 5–7 days leads to higher wastage due to expiry. To address this massive financial burden on the healthcare system, alternative applications for expired PC have emerged in recent years. Engineered nanocarriers functionalized with platelet membranes have shown excellent targeting abilities for tumor cells owing to their platelet membrane proteins. Nevertheless, synthetic drug delivery strategies have significant drawbacks that platelet-derived extracellular vesicles (pEV) can overcome. We investigated, for the first time, the use of pEV as a carrier of the anti-breast cancer drug paclitaxel, considering it as an appealing alternative to improve the therapeutic potential of expired PC. The pEV released during PC storage showed a typical EV size distribution profile (100–300 nm) with a cup-shaped morphology. Paclitaxel-loaded pEV showed significant anti-cancer effects in vitro, as demonstrated by their anti-migratory (>30%), anti-angiogenic (>30%), and anti-invasive (>70%) properties in distinct cells found in the breast tumor microenvironment. We provide evidence for a novel application for expired PC by suggesting that the field of tumor treatment research may be broadened by the use of natural carriers.

Cell-penetrating peptides (CPPs) have great potential to deliver bioactive agents into cells. Although there have been many recent advances in CPP-related research, it is still important to develop more efficient CPPs. The development of CPPs by in silico methods is a very useful addition to experimental methods, but in many cases it can lead to a large number of false-positive results. In this study, we developed a deep-learning-based CPP prediction method, AiCPP, to develop novel CPPs. AiCPP uses a large number of peptide sequences derived from human-reference proteins as a negative set to reduce false-positive predictions and adopts a method to learn small-length peptide sequence motifs that may have CPP tendencies. Using AiCPP, we found that short peptide sequences derived from amyloid precursor proteins are efficient new CPPs, and experimentally confirmed that these CPP sequences can be further optimized.

Bioactive linear poly(ionic liquid)s (PIL) were designed as carriers in drug delivery systems (DDS). Their synthesis was based on a monomeric ionic liquid (MIL) with a relevant pharmaceutical anion to create therapeutically functionalized monomers, which further can be used in the controlled atom transfer radical polymerization (ATRP). The presence of chloride counterions in the quaternary ammonium groups of choline MIL, e.g., [2-(methacryloyloxy)ethyl]trimethyl-ammonium chloride (ChMACl), was stimulated to undergo the anion exchange with p-aminosalicylate sodium salt (NaPAS) as the source of the pharmaceutical anion with antibacterial activity. The resultant [2-(methacryloyloxy)ethyl]trimethylammonium p-aminosalicylate (ChMAPAS) was copolymerized to attain the well-defined linear choline-based copolymers with various contents of PAS anions (24–42%), which were regulated by the initial ratio of ChMAPAS to MMA and conversion degree. The length of polymeric chains was evaluated by the total monomer conversion (31–66%) yielding degree of polymerization (DPn = 133–272). Depending on the polymer carrier composition, PAS anions were exchanged by 60–100% within 1 h, 80–100% within 4 h, and completely after 24 h by phosphate anions in PBS imitating a physiological fluid.

This work reports the use of mesoporous silica rods as templates for the step-wise preparation of multifunctional Fe3O4 NPs filled polydopamine hollow rods (Fe3O4@PDA HR). The capacity of as-synthesized Fe3O4@PDA HR as a new drug carrier platform was assessed by its loading and the triggered release of fosfomycin under various stimulations. It was found that the release of fosfomycin was pH dependent with ~89% of fosfomycin being released in pH 5 after 24 h, which was 2-fold higher than that in pH 7. The magnetic properties of Fe3O4 NPs and the photothermal properties of PDA enabled the triggered release of fosfomycin upon the exposure to rotational magnetic field, or NIR laser irradiation. Additionally, the capability of using multifunctional Fe3O4@PDA HR to eliminate preformed bacterial biofilm was demonstrated. Upon exposure to the rotational magnetic field, the biomass of a preformed biofilm was significantly reduced by 65.3% after a 20 min treatment with Fe3O4@PDA HR. Again, due to the excellent photothermal properties of PDA, a dramatic biomass decline (72.5%) was achieved after 10 min of laser exposure. This study offers an alternative approach of using drug carrier platform as a physical mean to kill pathogenic bacteria along with its traditional use for drug delivery.

Immune system is essential for host homeostasis. Immune cells communicate with each other by binding to receptors or by releasing vesicles including chemokines and cytokines. Under healthy circumstances, immune cell-derived factors are critical for cellular growth, division and function, whereas under conditions such as ageing and inflammatory states, they can aggravate pathologies and cause disease. Cell-derived membranous extracellular vesicles mediate cell-to-cell communication and are implicated in various physiological and pathological processes involving ageing and age-related diseases. Extracellular vesicles are responsible for spreading detrimental factors to the surroundings and the propagation phase of inflammatory diseases. The regulation of extracellular vesicles is a putative target for treatment of inflammatory diseases. Moreover, their features are ideal for developing biomarkers and drug delivery systems modulated by bioengineering in inflammatory diseases. The present review summarizes the current understanding of extracellular vesicles in ageing and inflammatory diseases.

Low temperature plasma (LTP) technology has shown an outstanding application value in the pharmaceutical filed in recent ten years. This paper reviews the research advances in LTP, including its effects on enhancing or inhibiting drug activity, its combined use with drugs to treat cancers, its effects on the improvement of drug delivery system, its use in preparation of new inactivated virus vaccines, its use with mass spectrometry for rapid detection of drug quality, and the anti-tumor and sterilization effects of plasma-activated liquids. The paper also analyzes the challenges of LTP in the pharmaceutical filed, hoping to promote related research., Graphical abstract Image 1, Highlights • Low temperature plasma is a young subject. It shows infinite possibilities in many fields. • Paper introduces the research advances on low temperature plasma in pharmaceutical field for the first time. • Paper summarizes the difficulties in the application of low temperature plasma in pharmacy.

A reversible switchable on-demand UV-triggered drug delivery system (DDS) based on interpenetrating polymer networks (IPNs) with silicone as the host polymer and spiropyran (SP)-functionalized guest polymer is designed and demonstrated. The photo-responsive IPNs provide a new triggered drug delivery concept as they exploit the change in intermolecular interactions (work of adhesion) among the drug, matrix, and solvent when the incorporated hydrophobic SP moieties transform into the hydrophilic merocyanine form upon light irradiation without degradation and disruption of the DDS. The change in how the copolymer composition (hydrophilicity and content) and the lipophilicity of the drug (log P) affect the release profile was investigated. A thermodynamic model, based on Hansen solubility parameters, was developed to design and optimize the polymer composition of the IPNs to obtain the most efficient light-triggered drug release and suppression of the premature release. The developed IPNs showed excellent result for dopamine, l-dopa, and prednisone with around 90-95% light-triggered release. The model was applied to study the release behavior of drugs with different log P and to estimate if the light-induced hydrophobic-to-hydrophilic switch can overcome the work of adhesion between polymers and drugs and hence the desorption and release of the drugs. To the best of our knowledge, this is the first time that work of adhesion is used for this aim. Comparing the result obtained from the model and experiment shows that the model is useful for evaluating and estimating the release behavior of specific drugs merocyanine, IPN, DDS, and spiropyran.

Biodegradable polyurethanes can be the basis for drug delivery systems that are sensitive to external changes. pH-sensitive polyurethanes (PUs) have been used successfully as intravaginal rings and specific drug delivery systems for the colon. In this study, a series of pH-sensitive polyurethane hydrogels with a change of the polyol component (poly(ethylene glycol) 400/poly(propylene glycol) 2000/poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol) 1100), saccharides as crosslinkers (melibiose/raffinose/starch) and a-hydroxy carboxylic acids as chain extenders (dimethylol propionic acid/lactic acid) were synthesized. Structural characterization of the synthesized polyurethane hydrogels was performed using Fourier transform infrared spectroscopy (FTIR), which showed that the polyurethane synthesis reaction was achieved with successful crosslinking with saccharides and, despite the change of starting components, FTIR spectra for all investigated samples are almost identical. The degree of swelling of the hydrogels was monitored at 25 °C in solutions of pH values 4.5 and 7.4. In samples with the polyol component block1100, the degree of swelling at pH 7.4 (16.09%) was up to 9 times higher than at pH 4.5 (1.82%). The effects of variable parameters on the thermal properties and phase transitions of PUs hydrogels were investigated by thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). The results showed that by varying the saccharide as a crosslinker, the acid chain extender and the chain length of the polyols, the stated properties of polyurethane hydrogels as potential drug delivery carriers can be influenced.

Fibrosis is a necessary process in the progression of chronic disease to cirrhosis or even cancer, which is a serious disease threatening human health. Recent studies have shown that the early treatment of fibrosis is turning point and particularly important. Therefore, how to reverse fibrosis has become the focus and research hotspot in recent years. So far, the considerable progress has been made in the development of effective anti-fibrosis drugs and targeted drug delivery. Moreover, the existing research results will lay the foundation for more breakthrough delivery systems to achieve better anti-fibrosis effects. Herein, this review summaries anti-fibrosis delivery systems focused on three major organ fibrotic diseases such as liver, pulmonary, and renal fibrosis accompanied by the elaboration of relevant pathological mechanisms, which will provide inspiration and guidance for the design of fibrosis drugs and therapeutic systems in the future., Graphical abstract Image, graphical abstractSummarizing the recent advances in liver, lung, and renal fibrosis accompanied by the elaboration of relevant pathological mechanisms as well as related treatment strategies, and development of anti-fibrotic drug delivery system

Weipeng Wei,1– 3,* Jianhua Tang,4,* Hongfang Li,1– 3 Yongsheng Huang,5 Chengchen Yin,1– 3 Dan Li,6 Fushan Tang1– 3 1Department of Clinical Pharmacy, Key Laboratory of Basic Pharmacology of Guizhou Province and School of Pharmacy, Zunyi Medical University, Zunyi 563000, People’s Republic of China; 2Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi 563000, People’s Republic of China; 3Key Laboratory of Clinical Pharmacy of Zunyi City, Zunyi Medical University, Zunyi 563000, People’s Republic of China; 4Cancer Research UK Manchester Institute, The University of Manchester, Cheshire SK10 4TG, UK; 5Peking Union Medical College, Chinese Academy of Medical Sciences, Institute of Basic Medical Sciences, Beijing 100005, People’s Republic of China; 6State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, People’s Republic of China*These authors contributed equally to this workCorrespondence: Fushan TangDepartment of Clinical Pharmacy, School of Pharmacy, Zunyi Medical University, Guizhou, People’s Republic of ChinaTel +86851 28642337Fax +86851 28642334Email fstang@vip.163.comDan LiCancer Hospital, Chinese Academy of Medical Sciences, Beijing, People’s Republic of ChinaTel +8610 87787107Email eileenld@gmail.comPurpose: To study the in vitro and in vivo antitumor effects of the colloidal suspension-in situ hydrogel of emodin (EM) constructed with the self-assembling peptide RADA16-I and systematically evaluate the feasibility of the delivery system.Methods: The MTT and colony-formation assays were used to determine the viability of normal cells NCTC 1469 and tumor cells Hepa1-6. The uptake of EM in the RADA16-I-EM in situ hydrogel by tumor cells was analyzed by laser confocal microscope and flow cytometry. Flow cytometry was used to detect the cell apoptosis and cell cycle distribution. Transwell assay was used to detect the migration and invasion of tumor cells. The antitumor efficacy of the RADA16-I-EM in situ hydrogel and its toxic effects was further assessed in vivo on Hepa1-6 tumor-bearing C57 mice.Results: The results showed that the RADA16-I-EM in situ hydrogels could obviously reduce the toxicity of EM to normal cells and the survival of tumor cells. The uptake of EM by the cells from the hydrogels was obviously increased and could significantly induce apoptosis and arrest cell cycle in the G2/M phase, and reduce the migration, invasion and clone-formation ability of the cells. The RADA16-I-EM in situ hydrogel could also effectively inhibit the tumor growth and obviously decrease the toxic effects of EM on normal tissues in vivo.Conclusion: Our results demonstrated that RADA16-I has the potential to be a carrier for the hydrophobic drug EM and can effectively improve the delivery of hydrophobic antitumor drugs with enhanced antitumor effects and reduced toxic effects of the drugs on normal cells and tissues.Keywords: self-assembling peptide, emodin, in situ hydrogels, antitumor, drug delivery system

Traditional drugs are facing bottlenecks of lower solubility, absorption, and especially the inefficient organs or cells targeting during the precision medicine era. It is urgently needed to discover and establish new methods or strategies to modify old drugs or create new ones against the above defects. With the support of nanotechnology, the solubility, absorption and targeting of traditional drugs were greatly improved by modifying and fabricating with various types of nanoparticles to some extent, though many shortages remain. In this mini-review we will focus on advances in several most commonly used nanoparticles, from their nature and design, to drug delivery system and clinical application, that they overcome heterogeneous barriers in precision medicine, thereby ultimately improve patient outcome overall.

Emulsion electrospinning is a method of modifying a fibers’ surface and functional properties by encapsulation of the bioactive molecules. In our studies, bovine serum albumin (BSA) played the role of the modifier, and to protect the protein during the electrospinning process, the W/O (water-in-oil) emulsions were prepared, consisting of polymer and micelles formed from BSA and anionic (sodium dodecyl sulfate–S) or nonionic (Tween 80–T) surfactant. It was found that the micelle size distribution was strongly dependent on the nature and the amount of the surfactant, indicating that a higher concentration of the surfactant results in a higher tendency to form smaller micelles (4–9 µm for S and 8–13 µm for T). The appearance of anionic surfactant micelles reduced the diameter of the fiber (100–700 nm) and the wettability of the nonwoven surface (up to 77°) compared to un-modified PCL polymer fibers (100–900 nm and 130°). The use of a non-ionic surfactant resulted in better loading efficiency of micelles with albumin (about 90%), lower wettability of the nonwoven fabric (about 25°) and the formation of larger fibers (100–1100 nm). X-ray photoelectron spectroscopy (XPS) was used to detect the presence of the protein, and UV-Vis spectrophotometry was used to determine the loading efficiency and the nature of the release. The results showed that the location of the micelles influenced the release profiles of the protein, and the materials modified with micelles with the nonionic surfactant showed no burst release. The release kinetics was characteristic of the zero-order release model compared to anionic surfactants. The selected surfactant concentrations did not adversely affect the biological properties of fibrous substrates, such as high viability and low cytotoxicity of RAW macrophages 264.7.

Conventional drug delivery systems often cause side effects and gastric degradation. Novel drug delivery systems must be developed to decrease side effects and increase the efficacy of drug delivery. This research aimed to fabricate hydrogel beads for use as a drug delivery system based on basil seed mucilage (BSM), sodium alginate (SA), and magnetic particles (MPs). The Taguchi method and Grey relational analysis were used for the design and optimization of the hydrogel beads. Three factors, including BSM, SA, and MPs at four levels were designed by L-16 orthogonal arrays. BSM was the main factor influencing bead swelling, drug release rate at pH 7.4, and release of antioxidants at pH 1.2 and 7.4. In addition, SA and MPs mainly affected drug loading and drug release rate in acidic medium, respectively. Grey relational analysis indicated that the composition providing optimal overall properties was 0.2 vol% BSM, 0.8 vol% SA, and 2.25 vol% MPs. Based on the findings of this work, BSM/SA/MPs hydrogel beads have the potential to be used as a pH-sensitive alternative material for drug delivery in colon-specific systems.

New strategies to efficiently treat bacterial infections are crucial to circumvent the increase of resistant strains and to mitigate side effects during treatment. Skin and soft tissue infections represent one of the areas suffering the most from these resistant strains. We developed a new drug delivery system composed of the green algae, Chlamydomonas reinhardtii, which is generally recognized as safe, to target specifically skin diseases. A two‐step functionalization strategy was used to chemically modify the algae with the antibiotic vancomycin. Chlamydomonas reinhardtii was found to mask vancomycin and the insertion of a photocleavable linker was used for the release of the antibiotic. This living drug carrier was evaluated in presence of Bacillus subtilis and, only upon UVA1‐mediated release, growth inhibition of bacteria was observed. These results represent one of the first examples of a living organism used as a drug delivery system for the release of an antibiotic by UVA1‐irradiation., Algae control the release: A new approach for antibiotic caging and controlled release was developed using Chlamydomonas reinhardtii. The algae were covalently modified with vancomycin, and using a photocleavable linker, light‐mediated release of an antibacterial agent from the cell surface and inhibited the growth of Bacillus subtilis (see figure).