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The eye's complex anatomical structures present formidable barriers to effective drug delivery across a range of ocular diseases, from anterior to posterior segment pathologies. Emerging as a promising solution to these challenges, nanotechnology-based platforms-including but not limited to liposomes, dendrimers, and micelles-have shown the potential to revolutionize ophthalmic therapeutics. These nanocarriers enhance drug bioavailability, increase residence time in targeted ocular tissues, and offer precise, localized delivery, minimizing systemic side effects. Focusing on pediatric ophthalmology, particularly on retinoblastoma, this review delves into the recent advancements in functionalized nanosystems for drug delivery. Covering the literature from 2017 to 2023, it comprehensively examines these nanocarriers' potential impact on transforming the treatment landscape for retinoblastoma. The review highlights the critical role of these platforms in overcoming the unique pediatric eye barriers, thus enhancing treatment efficacy. It underscores the necessity for ongoing research to realize the full clinical potential of these innovative drug delivery systems in pediatric ophthalmology.

Polyhedral oligomeric silsesquioxanes (POSS) have attracted considerable attention in the design of novel organic-inorganic hybrid materials with high performance capabilities. Features such as their well-defined nanoscale structure, chemical tunability, and biocompatibility make POSS an ideal building block to fabricate hybrid materials for biomedical applications. This review highlights recent advances in the application of POSS-based hybrid materials, with particular emphasis on drug delivery, photodynamic therapy and bioimaging. The design and synthesis of POSS-based materials is described, along with the current methods for controlling their chemical functionalization for biomedical applications. We summarize the advantages of using POSS for several drug delivery applications. We also describe the current progress on using POSS-based materials to improve photodynamic therapies. The use of POSS for delivery of contrast agents or as a passivating agent for nanoprobes is also summarized. We envision that POSS-based hybrid materials have great potential for a variety of biomedical applications including drug delivery, photodynamic therapy and bioimaging.

Poly(ethylene glycol) diacrylate (PEGDA) is a common polymer in the field of biomedical engineering and can be used for the production of drug delivery systems (DDS). The main advantages of PEGDA are biocompatibility and the ability to alter the physical and chemical properties, thereby ensuring individualized drug release behaviour. The processing of PEGDA via inkjet printing is relevant for the production of DDS. This can be challenging due to the high viscosity of pure PEGDA. In this work, PEGDA, with a molecular weight of 250 g/mol (PEGDA250), was inkjet printed using a Nanoplotter 2.1 with a piezoelectric heatable NanoTip HV-J-H printhead (GeSiM mbH, Radeberg, Germany) at different voltages and temperatures. Droplet generation was analysed in terms of droplet volume and angle deviations. PEGDA250 can be inkjet printed reproducibly in a voltage range of 60 V - 80 V at room temperature (20 °C) or heated up to 38 °C. The average volume of heated (38 °C) PEGDA250 droplets was approximately 110 pl - 150 pl higher than the droplet volume of PEGDA250 in the unheated state. The average angle deviations of main and satellite droplets were mostly < 3°. Increasing voltage or excessive heating of more than 38 °C caused greater instabilities in the droplet generation as well as larger satellite droplets which can affect the accuracy negatively. The studies have shown that PEGDA250 can be processed via inkjet printing and thus can be used as a drug carrier for DDS without the need for mixing with a solvent. [ABSTRACT FROM AUTHOR]

This paper provides a review of the literature on the use of Pluronic® triblock copolymers for drug encapsulation over the last 10 years. A special focus is given to the progress of drug delivery systems (e.g. , micelles, liposomes, micro/nanoemulsions, hydrogels and nanogels, and polymersomes and niosomes); the beneficial aspects of Pluronic® triblock copolymers as biological response modifiers and as pharmaceutical additives, adjuvants, and stabilizers, are also discussed. The advantages and limitations encountered in developing site-specific targeting approaches based on Pluronic-based nanostructures in cancer treatment are highlighted, in addition to innovative examples for improving tumor cytotoxicity while reducing side effects. [Display omitted] [ABSTRACT FROM AUTHOR]

The goal of this research was the development of cellulose-based biodegradable drug delivery systems solutions for cosmetic mask applications. Cellulose-based materials derived from natural renewable sources provide a sustainable alternative to nonwoven cosmetic masks derived from nondegradable fossil-based raw materials. An experimental design was executed to assemble the 3D cellulose fibres matrix and the water in oil emulsion comprising the active molecules from Mentha piperita L. Two types of biopolymeric additives were used, one derived from a nano/micro fibrillated cellulose pulp and another one including chitosan. A 3D computational simulation study was performed to enhance porosity and strength properties. The results indicated that the cosmetic face mask optimized prototypes, made from a biodegradable 3D matrix of cellulose fibres and active molecules, are suitable for dermic use. [ABSTRACT FROM AUTHOR]

Anthracyclines are effective anticancer drugs but have drawbacks including systemic toxicity and drug resistance. Delivering them directly to the tumor may improve therapeutic efficacy and reduce adverse effects. Carbon nanotubes (CNTs) can act as excellent drug delivery systems (DDS), but pristine CNTs have inert surfaces, which contributes poor drug loading capacity and limits dispersion. In this study, we designed a series of functionalized CNTs (f-CNTs) with anchored hydrophilic groups (OH, COOH, and NH 2 ) by substitutional doping of the CNT lattice (DNT) using N or B atoms or the combination of both. The aromatic compound benzene (Ben) was selected as a model for anthracycline drugs. The effect of CNT curvature, chemical groups (CGs), and doping on the Ben-CNTs interactions was studied using quantum chemistry calculations. Our results show that π-π interactions between Ben and CNTs are influenced by CNT curvature. When the CNTs were functionalized only with CGs and not doped, the system was unstable, resulting in weak Ben-CNT interactions. However, anchoring CGs on DNTs greatly enhanced the Ben-CNT interactions. CNTs with good affinity for drug molecules, improved solubility, and lower tendency to aggregate have potential as DDS for enhancing the efficacy of medicines. We believe that these studies have general applicability and anticipate that our findings will motivate additional theoretical and experimental studies on the biology and chemistry of CNTs as DDS. [ABSTRACT FROM AUTHOR]

A drug delivery system is used for targeting drugs to specific cells. Various drug carriers, that also reduce the side effects of unbound drugs, have been introduced and commercialized in the pharmaceutical field. Among them, synthetic biodegradable polymers have received much attention attributed to their low toxicity, controllable biodegradation rates, manufacturability, and low costs. This paper reviews the salient characteristics of biodegradable polymers as drug carriers and their microfabrication methods. The reviewed microfabrication methods include laser micromachining, rapid prototyping, replication, emulsification, microfluidic fabrication, and X-ray-lithography-based methods. For these microfabrication methods, critical dimensions, feature variety, solvent compatibility, production throughput, and tooling requirements are also summarized. [ABSTRACT FROM AUTHOR]

Understanding the structure-property relationships of drug delivery system (DDS) components is critical for their development and the prediction of bodily performance. This study investigates the effects of introducing polyethylene oxide (PEO) homopolymers, over a wide range of molecular weights, into Pluronic injectable smart hydrogel formulations. These smart DDSs promise to enhance patient compliance, reduce adverse effects and dosing frequency. Pharmaceutically, Pluronic systems are attractive due to their unique sol-gel phase transition in the body, biocompatibility, safety and ease of injectability as solutions before transforming into gel matrices at body temperature. This paper presents a systematic and comprehensive evaluation of gelation and the interplay of microscopic and macroscopic properties under both equilibrium and non-equilibrium conditions in controlled environments, as measured by rheology in conjunction with time-resolved Small Angle Neutron Scattering (SANS). The non-equilibrium conditions investigated in this work offer a better understanding of the two polymeric systems' complex interactions affecting the matrix thermo-rheological behaviour and structure and therefore the future release of an active pharmaceutical ingredient from the injectable DDS. [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract: Used since ancient times especially for the local treatment of pulmonary diseases, lungs and airways are a versatile target route for the administration of both local and systemic drugs. Despite the existence of different platforms and devices for the pulmonary administration of drugs, only a few formulations are marketed, partly due to physiological and technological limitations. Respiratory infections represent a significant burden to health systems worldwide mainly due to intrahospital infections that more easily affect immune-compromised patients. Moreover, tuberculosis (TB) is an endemic infectious disease in many developing nations and it has resurged in the developed world associated with the human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) epidemic. Currently, medicine faces the specter of antibiotic resistance. Besides the development of new anti-infectious drugs, the development of innovative and more efficient delivery systems for drugs that went off patent appears as a promising strategy pursued by the pharmaceutical industry to improve the therapeutic outcomes and to prolong the utilities of their intellectual property portfolio. In this context, nanotechnology-based drug delivery systems (nano-DDS) emerged as a promising approach to circumvent the limitations of conventional formulations and to treat drug resistance, opening the hypothesis for new developments in this area. [Copyright &y& Elsevier]

Abstract: Current treatments for Parkinson's disease (PD) are aimed at addressing motor symptoms but there is no therapy focused on modifying the course of the disease. Successful treatment strategies have been so far limited and brain drug delivery remains a major challenge that restricts its treatment. This review provides an overview of the most promising emerging agents in the field of PD drug discovery, discussing improvements that have been made in brain drug delivery for PD. It will be shown that new approaches able to extend the length of the treatment, to release the drug in a continuous manner or to cross the blood–brain barrier and target a specific region are still needed. Overall, the results reviewed here show that there is an urgent need to develop both symptomatic and disease-modifying treatments, giving priority to neuroprotective treatments. Promising perspectives are being provided in this field by rasagiline and by neurotrophic factors like glial cell line-derived neurotrophic factor. The identification of disease-relevant genes has also encouraged the search for disease-modifying therapies that function by identifying molecularly targeted drugs. The advent of new molecular and cellular targets like α-synuclein, leucine-rich repeat serine/threonine protein kinase 2 or parkin, among others, will require innovative delivery therapies. In this regard, drug delivery systems (DDS) have shown great potential for improving the efficacy of conventional and new PD therapy and reducing its side effects. The new DDS discussed here, which include microparticles, nanoparticles and hydrogels among others, will probably open up possibilities that extend beyond symptomatic relief. However, further work needs to be done before DDS become a therapeutic option for PD patients. [Copyright &y& Elsevier]

A promising approach for local drug delivery is high-intensity focused ultrasound (HIFU)-triggered release of drugs from stimuli-responsive nanoparticles such as liposomes. The aim of this study was to investigate whether another release mechanism is involved with HIFU-triggered release from liposomes beside cavitation and temperature. Furthermore, it was studied whether this new release mechanism allows the release of lipophilic compounds. Therefore, both a lipophilic (Nile red) and a hydrophilic (fluorescein) compound were loaded into thermosensitive (TSL) or non-thermosensitive liposomes (NTSL) and the liposomes were subjected both to continuous wave (CW)- and pulsed wave (PW)-HIFU. The mean liposome size varied from 97 to 139nm with a polydispersity index (PDI)≤0.06 for the different formulations. The T m of the phospholipid bilayer of the TSL was around 42°C. Approximately 80% of fluorescein was released within 15min from TSL at temperatures≥42°C. In contrast, no fluorescein release from NTSL and NR release from both TSL and NTSL was observed at temperatures up to 60°C. CW-HIFU exposure of TSL resulted in rapid temperature elevation up to 52°C and subsequently almost quantitative fluorescein release. Fluorescein release from NTSL was also substantial (~64% after 16min at 20W). Surprisingly, CW-HIFU exposure (20W for 16min) resulted in the release of NR from TSL (~66% of the loaded amount), and this was even higher from NTSL (~78%). PW-HIFU exposure did not result in temperatures above the T m of TSL. However, nearly 85% of fluorescein was released from TSL after 32min at 20W of PW-HIFU exposure, whereas the release from NTSL was around 27%. Interestingly, NR release from NTSL was~30% after 2min PW-HIFU exposure and increased to~70% after 32min. Furthermore, addition of microbubbles to the liposomes prior to PW-HIFU exposure did not result in more release, which suggests that cavitation can be excluded as the main mechanism responsible for the triggered release of both a hydrophilic and a lipophilic model compound from liposomes. Dynamic light scattering analysis showed that the mean size and PDI of the liposomes did not significantly change after CW- and PW-HIFU exposure. Taken together, it is therefore concluded that neither temperature elevation nor inertial cavitation is essential for the release of both hydrophilic and lipophilic compounds from liposomes. It is assumed that the release originates from radiation force-induced acoustic streaming, causing the liposomes to collide at the walls of the exposure chamber leading to shear forces which in turn results in reversible liposome destabilization and release of both hydrophilic and lipophilic compounds. [ABSTRACT FROM AUTHOR]

Abstract: At report, we presented a common design and theoretical modelling scheme for a porous scaffold from nitinol with a shape memory effect (SME), fabricated by the selective laser sintering (SLS) process. The operation of the SME fluidic MEMS involves such physical process as heat transfer, phase transformation with temperature hysteresis, stress-strain and electrical resistance variations accompanying the phase transformation. This model can be used for an estimation of drug delivery system (DDS) route during a porous volume changing. [Copyright &y& Elsevier]

Abstract: Electrohydrodynamic atomization (EHDA) is an attractive technique to make new types of composite particles for pharmaceutical use. The aim of this work is to prove that EHDA can be successfully used to attach nano/micro-particles of protein to lactose, the commonly used excipient for pulmonary delivery, keeping all the biological properties of the protein after dissolution of the complex. Bovine serum albumin (BSA) was used as a model protein. The atomization of BSA was tested with two different solvents, dimethyl sulfoxide (DMSO) and ethanol. The process using DMSO resulted in the formation of a thin layer of protein while the tests using ethanol resulted in the formation of spherical particles with mean diameters around 700nm. Ethanol as solvent was also used to produce a composite formed by BSA adsorbed at the surface of lactose by electrostatic forces. No denaturation or significant conformational changes of the protein were observed, although an increase in the exposition of the lactose to the jet of the solution decreases the reproducibility of the method. Due to the absence of denaturation in the model protein, this new approach can be tested for the production of new formulations for dry powders for drug delivery systems. [Copyright &y& Elsevier]

Summary: Targeted delivery of anti-tubercular therapeutics to alveolar macrophages via inhalation aims to achieve optimal concentration of the therapeutic in the mycobacteria’s niche environment. However, several challenges need to be overcome when designing a system to achieve this targeted, intracellular delivery. The first objective is to design a system that is suitable for inhalation, i.e. it must be capable of deposition in the alveolar region of the lungs. The theme of this commentary will be on the biological barriers for intracellular targeting to alveolar macrophages once particles are deposited in the lungs with emphasis on the delivery of anti-tubercular therapy and implications for novel vaccine formulations. The commentary focuses on four key features: 1) How Mycobacterium tuberculosis enters and is trafficked through macrophages, 2) the mechanism by which current drug delivery systems (DDS) enter and are trafficked through cells and 3) How an ideal DDS for anti-tubercular therapy would be trafficked through the macrophage and 4) the potential for using DDS for novel anti-tubercular therapy and vaccine development. These four features of targeted DDS shall be discussed in relation to some new findings from our own research. [ABSTRACT FROM AUTHOR]

Abstract: Worldwide, over 40 million people are infected with the Human Immunodeficiency Virus (HIV). The High Activity Antiretroviral Therapy (HAART) combines at least three antiretroviral (ARV) drugs and, for over a decade, has been used to extend the lifespan of the HIV-infected patients. Chronic intake of HAART is mandatory to control HIV infection. The frequent administration of several drugs in relatively high doses is a main cause of patient incompliance and a hurdle toward the fulfillment of the pharmacotherapy. High adherence to HAART does not lead to complete HIV virus elimination from the host. Intracellular and anatomical viral reservoirs are responsible for the perpetuation of the infection. Active transport mechanisms involving proteins of the ATP-binding cassette superfamily prevent the penetration of ARV drugs into the brain and may account for the limited bioavailability after oral administration. A new research that addresses from simple organoleptic or technological problems to more complex issues involving the targeting of specific tissues and organs has emerged. With the aim to reduce dosing frequency, to improve the compliance of the existing pharmacotherapy and to target viral reservoirs, the design of drug delivery systems (DDS) is becoming complementary to new drug discovery. Based on the common molecular features that characterize the different families of ARV drugs, the present review describes state-of-the-art ARV DDS and thoroughly discusses the challenges in the development of medicines with enhanced biopharmaceutical properties. In addition, a number of specific issues such as pediatric HAART, preventive pharmacotherapy and specific HIV-associated ethical issues are addressed in an integrative manner. Finally, the impact of such novel drug development on the Pharmaceutical Technology field is discussed. [Copyright &y& Elsevier]

Abstract: In this work a multifaceted approach to the fabrication of scaffolds is considered, that is, besides the preparation technique, the introduction of substances that may contribute to enhance their final performance, as well as the techniques required to ensure the correct preservation of the so obtained scaffolds are taken into account to tailor the release of vancomycin from β-tricalcium phosphate (β-TCP)/agarose scaffolds. These materials were prepared by a shaping technique that allows to obtain pieces at a temperature low enough to simultaneously include active substances susceptible of heat degrading such as vancomycin, the model drug considered in this work. In the first approximation poly(ethylene glycol) (PEG), a hydrophilic substance employed as a matrix capable of binding compounds such as proteins or peptides and release them in a controlled fashion, was included in the formulation. The second tool to govern the vancomycin liberation is based on the drying procedures employed to process and preserve the obtained scaffolds: freeze-drying and heat desiccation at 37°C. These modifications resulted in the generation of different pore architectures and certain chemical interactions, such as the formation of an agarose–PEG–vancomycin complex that yielded different drug release patterns. The so obtained pieces behave like a hydrogel when immersed in a hydrated medium but show a consistency comparable to that of the cancellous bone. [Copyright &y& Elsevier]

Use of macromolecular water-soluble carriers of anti-cancer drugs represents a promising approach to cancer therapy. Release of drugs from the carrier system is a prerequisite for therapeutic activity of most macromolecular anti-cancer conjugates. Incorporation of acid-sensitive spacers between the drug and carrier enables release of an active drug from the carrier in a tumor tissue, either in slightly acidic extracellular fluids or, after endocytosis, in endosomes or lysosomes of cancer cells. This paper reviews advances in development and study of properties of various acid-sensitive macromolecular drug delivery systems, starting from simple polymer–drug conjugates to ending with site-specific antibody-targeted polymer–drug conjugates. [Copyright &y& Elsevier]

[Display omitted] Curcumin (CUR) is a phenolic compound present in some herbs, including Curcuma longa Linn. (turmeric rhizome), with a high bioactive capacity and characteristic yellow color. It is mainly used as a spice, although it has been found that CUR has interesting pharmaceutical properties, acting as a natural antioxidant, anti-inflammatory, antimicrobial, and antitumoral agent. Nonetheless, CUR is a hydrophobic compound with low water solubility, poor chemical stability, and fast metabolism, limiting its use as a pharmacological compound. Smart drug delivery systems (DDS) have been used to overcome its low bioavailability and improve its stability. The current work overviews the literature from the past 10 years on the encapsulation of CUR in nanostructured systems, such as micelles, liposomes, niosomes, nanoemulsions, hydrogels, and nanocomplexes, emphasizing its use and ability in cancer therapy. The studies highlighted in this review have shown that these nanoformulations achieved higher solubility, improved tumor cytotoxicity, prolonged CUR release, and reduced side effects, among other interesting advantages. [ABSTRACT FROM AUTHOR]

One of the major challenges in the field of biomedicine is to use biocompatible carriers to achieve efficient drug delivery in the body. Most of the existing carriers have shown poor loading and rapid drug release. In this context, a subclass of coordination polymers, known as Metal-Organic Frameworks (MOFs), has attracted huge research interest: the unique physical properties of MOFs make them exceptional materials for drug delivery systems. Here, we have synthesized and characterized a non-toxic Zn-based MOF, designated bio-MOF-1, by using 4,4′-biphenyl-dicarboxylic acid and adenine as linkers. The microcrystalline porous material presented great loading capacity (0.340 ​g·g−1) for the antitumoral metallodrug Ru-90 [ cis -[Ru(bpy) 2 (NO 2)(solv)](PF 6)]. The cellular viability results demonstrated that metallodrug occlusion facilitated its access and increased its availability in the cells. Ru-90 release from bio-MOF-1 depended on pH, so this material is a promising candidate for anticancer drug delivery. Moreover, application of kinetic equation models revealed that the mechanism of Ru-90 release from bio-MOF-1 fitted the Korsmeyer-Peppas model for the system at pH 5.0 and pH 7.4; the plots displayed high linearity and correlation coefficient values (R2) greater than 0.96. The n values were under 0.45 (Korsmeyer-Peppas model), which suggested the quasi Fickian model for the transport mechanism. In conclusion, the kinetic study results showed that bio-MOF-1 delivers the anticancer complex Ru-90 mostly through a diffusive mechanism. [Display omitted] • Synthesis of Bio-MOF-1, a non-toxic Zn-based MOF. • Bio-MOF-1 presented great Ru-90 complex, as antitumoral drug, loading capacity. • Ru-90 release was pH-sensitive showing a promising anticancer drug delivery. • Ru-90@Bio-MOF-1 had good selectivity index (SI) in the studied cell lines. [ABSTRACT FROM AUTHOR]

Zeolites have attractive features making them suitable carriers for drug delivery systems (DDS). As such, we loaded the anticancer drug 5-fluorouracil (5-FU), into two different zeolite structures, faujasite (NaY) and Linde Type L (LTL), to obtain different DDS. The prepared DDS were tested in vitro using breast cancer, colorectal carcinoma, and melanoma cell lines and in vivo using the chick embryo chorioallantoic membrane model (CAM). Both assays showed the best results for the Hs578T breast cancer cells, with a higher potentiation for 5-FU encapsulated in the zeolite LTL. To unveil the endocytic mechanisms involved in the internalization of the zeolite nanoparticles, endocytosis was inhibited pharmacologically in breast cancer and epithelial mammary human cells. The results suggest that a caveolin-mediated process was responsible for the internalized zeolite nanoparticles. Aiming to boost the DDS efficacy, the disc-shaped zeolite LTL outer surface was functionalized using amino (NH 2) or carboxylic acid (COOH) groups and coated with poly- l -lysine (PLL). Positively functionalized surface LTL nanoparticles revealed to be non-toxic to human cells and, importantly, their internalization was faster and led to a higher tumor reduction in vivo. Overall, our results provide further insights into the mechanisms of interaction between zeolite-based DDS and cancer cells, and pave the way for future studies aiming to improve DDS anticancer activity. Unlabelled Image • 5-FU DDS-based zeolite nanoparticles exhibit good anticancer efficacy in vitro and in vivo. • Zeolite nanoparticles are mainly internalized by a caveolin-mediated process in cancer cells. • NH 2 DDS functionalization increases their antitumoral activity in vivo. [ABSTRACT FROM AUTHOR]

The success of oil-based plastics and the continued growth of production and utilisation can be attributed to their cost, durability, strength to weight ratio, and eight contributions to the ease of everyday life. However, their mainly single use, durability and recalcitrant nature have led to a substantial increase of plastics as a fraction of municipal solid waste. The need to substitute single use products that are not easy to collect has inspired a lot of research towards finding sustainable replacements for oil-based plastics. In addition, specific physicochemical, biological, and degradation properties of biodegradable polymers have made them attractive materials for biomedical applications. This review summarises the advances in drug delivery systems, specifically design of nanoparticles based on the biodegradable polymers. We also discuss the research performed in the area of biophotonics and challenges and opportunities brought by the design and application of biodegradable polymers in tissue engineering. We then discuss state-of-the-art research in the design and application of biodegradable polymers in packaging and emphasise the advances in smart packaging development. Finally, we provide an overview of the biodegradation of these polymers and composites in managed and unmanaged environments. [ABSTRACT FROM AUTHOR]