Controlled Drug Release Kinetics Research Articles

Polymer-grafted porous silicon nanoparticles for enhanced siRNA delivery

Small interfering RNA (siRNA) shows promise for cancer treatment but faces biological barriers limiting its effective clinical use. To overcome these limitations and enhance siRNA’s therapeutic potential, innovative drug delivery systems are needed. Porous silicon nanoparticles (pSiNPs) are an attractive drug delivery system due to their high surface area, biodegradability, and tuneable porosity, although challenges with uncontrolled degradation, limited circulation time, and inefficient drug release remain. To address these limitations, we explored surface-initiated reversible addition-fragmentation chain transfer polymerisation to modify pSiNPs with poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) and poly(oligo(ethylene glycol) methacrylate) (POEGA). PDMAEMA, an ionisable polymer with tertiary amine groups, is protonated at physiological pH and facilitates strong electrostatic interactions with negatively charged siRNA, leading to an siRNA loading capacity up to 438 ± 21 μg/mg, but resulted in burst release. The addition of the outer POEGA block, with its hydrophilic and neutral properties, resulted in a similar loading efficiency and enabled a more controlled biphasic drug release kinetics, although it reduced cellular association. Both systems successfully protected the siRNA from RNAse degradation, showed good cytocompatibility, and successful delivered siRNA targeting polo-like kinase 1 (PLK1). These results suggest that these polymer-coated pSiNPs offer a promising approach for siRNA delivery and gene therapy.

A Comprehensive Review on Metal Oxide‐based Nanomaterials: Synthesis, Characterization, Environmental, and Therapeutic Applications

AbstractMetal oxide‐based nanomaterials have gained attention due to their unique properties and wide applications in numerous fields including environmental remediation and intervention therapy. This paper provides a comprehensive overview of the synthetic methods, characterization strategies, and therapeutic and environmental applications of metal oxide‐based NPs. Diverse synthetic routes have their advantages in controlling the nanostructure size, shape, and morphology of nanostructures and thus, tailoring their properties to specific applications techniques such as X‐ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and Fourier transform infrared spectroscopy (FTIR) provide information about crystallite size, morphology, surface chemistry, and optical properties. These NPs have the potential for the identification and elimination of hazardous gases, heavy metals like arsenic, iron, and manganese, and so on. along with organic pollutants and biological contaminants such as viruses, bacteria, and fungi. The medicinal utility of metal‐oxide‐based NPs has also been disseminated, particularly their role as antibacterial, antifungal, and anticancer agents. The properties may be attributed to high surface area (surface‐to‐volume ratio) and high reactivity. They also find applications in clinical medicine especially in drug delivery and biomedical imaging. Their biocompatibility, controlled drug release kinetics and ability to target cells or tissues make them more effective than conventional drugs.

Liposomal Formulations: A Recent Update.

Liposome-based drug delivery technologies have showed potential in enhancing medication safety and efficacy. Innovative drug loading and release mechanisms highlighted in this review of next-generation liposomal formulations. Due to poor drug release kinetics and loading capacity, conventional liposomes have limited clinical use. Scientists have developed new liposomal carrier medication release control and encapsulation methods to address these limits. Drug encapsulation can be optimized by creating lipid compositions that match a drug's charge and hydrophobicity. By selecting lipids and adding co-solvents or surfactants, scientists have increased drug loading in liposomal formulations while maintaining stability. Nanotechnology has also created multifunctional liposomes with triggered release and personalized drug delivery. Surface modification methods like PEGylation and ligand conjugation can direct liposomes to disease regions, improving therapeutic efficacy and reducing off-target effects. In addition to drug loading, researchers have focused on spatiotemporal modulation of liposomal carrier medication release. Stimuli-responsive liposomes release drugs in response to bodily signals. Liposomes can be pH- or temperature-sensitive. To improve therapeutic efficacy and reduce systemic toxicity, researchers added stimuli-responsive components to liposomal membranes to precisely control drug release kinetics. Advanced drug delivery technologies like magnetic targeting and ultrasound. Pro Drug, RNA Liposomes approach may improve liposomal medication administration. Magnetic targeting helps liposomes aggregate at illness sites and improves drug delivery, whereas ultrasound-mediated drug release facilitates on-demand release of encapsulated medicines. This review also covers recent preclinical and clinical research showing the therapeutic promise of next-generation liposomal formulations for cancer, infectious diseases, neurological disorders and inflammatory disorders. The transfer of these innovative liposomal formulations from lab to clinical practice involves key difficulties such scalability, manufacturing difficulty, and regulatory limits.

Ultrasound-triggered drug release and cytotoxicity of microbubbles with diverse drug attributes

Ultrasound-triggered drug release and cytotoxicity of microbubbles with diverse drug attributes

Alginate Microbeads Technology for Pharmaceutical Applications

Nowadays, microbeads are inevitable in pharmaceutical formulations with remarkable drug delivery and therapeutic outcome benefits. Usually made from biocompatible polymers, these tiny spherical particles allow for controlled and targeted delivery of APIs within the human body. Other benefits associated with microbeads include their ability to control drug release kinetics in terms of sustained or pulsatile release profiles in order to facilitate patient compliance and minimize adverse effects. This also has a minimal size and allows for adaptation for precise dosing and targeting the right sites, which augments therapeutic efficacy while cutting down systemic exposure. The need for safe and effective drug delivery systems has been a crucial aspect in the advancement of new pharmaceutical formulations. Researchers continue to seek new ways in prolonging drug release, minimizing drug wastage, and reducing the side effects of drugs. However, synthetic polymers are costly, non-biocompatible, and potentially toxic. On the other hand, sodium alginate, a natural polymer, is generally used as a matrix material because of biodegradability, low price, simplicity, and excellent biocompatibility. Sodium alginate is nontoxic when delivered orally and gives protection on the mucous membrane of the upper gastrointestinal tract. Sodium alginate is an anionic polysaccharide of natural origin wherein gelation can be obtained with the use of calcium ions to form stable microbeads. There are multiple techniques used to prepare alginate microbeads, that is, ionotropic gelation, cross-linking, emulsion gelation, spray drying, and both simple and complex coacervation phase separation methods. This review shall highlight the preparation and characterization of alginate microbeads, their therapeutic applications, and their position in the realm of controlled and novel drug delivery systems

Nanofiber-Based Drug Delivery Systems: A Review on Its Applications, Challenges, and Envisioning Future Perspectives.

Nanomaterials, especially nanofibers, hold considerable promise as drug delivery systems (DDS) by providing targeted administration of drugs due to their unique properties, such as large surface area, high porosity, and mechanical robustness. Nanofibers can be fabricated using various techniques like electrospinning, self-assembly, phase separation, and template synthesis, offering properties such as adjustable size, shape, high precision, and biodegradability. Additionally, features such as multiple target functionalization, controlled release of the drug, and prolonged circulation of the drug make nanofibers particularly suitable for biomedical applications, including drug delivery, tissue regeneration, and biosensing. This comprehensive review explores the characteristics, types, fabrication methods, and applications of nanofibers. Diverse types of polymer nanofibers are used in drug delivery, such as blended nanofibers, core-shell nanofibers, and layer-by-layer assembly, each demonstrating their own advantages in controlled drug release and targeted therapy. Electrospun nanofibers are extensively utilized in biomedical applications due to their superior mechanical performance and high porosity and advancements in coaxial electrospinning enabling the fabrication of core-shell nanofibers, offering controlled drug release kinetics and protection of loaded molecules. These nanofibers demonstrate enhanced bioactivity and biocompatibility and can find application in tissue engineering. Furthermore, this review addresses the challenges associated with nanofiber production, including reproducibility and scalability. Nanofibers exhibit the potential to revolutionize medical treatment across diverse therapeutic areas. Future research directions and challenges in nanofiber-based drug delivery discussed in this review offer guidance for further advancements in this rapidly evolving field.

A SYSTEMATIC REVIEW OF THE EFFECTIVENESS OF TURMERIC IN THE TREATMENT OF BREAST CANCER

Breast cancer remains a significant global health concern, necessitating the exploration of innovative therapeutic strategies. Curcumin, a bioactive compound derived from turmeric, has garnered considerable attention due to its diverse pharmacological properties, including anticancer effects. However, the clinical translation of curcumin is hampered by its poor bioavailability. Nanoformulations of curcumin, particularly Cur-NPs, offer a promising solution to this challenge by enhancing drug solubility, stability, and targeted delivery. This in-depth abstract delves into the potential of Cur-NPs as a therapeutic approach for breast cancer treatment. The systematic review included in vivo studies investigating the efficacy and toxicity of Cur-NPs in breast cancer models. Notably, Cur-NPs demonstrated significant antitumoral activity across diverse breast cancer models, attributed to mechanisms such as apoptosis induction, inhibition of proliferation, and suppression of angiogenesis. Moreover, Cur-NPs exhibited minimal toxicity, with no or low adverse effects observed in terms of body weight, organ histopathology, and hematological/biochemical parameters. Characterization of Cur-NPs revealed a diverse array of nanoparticle types, including polymer NPs, micelles, lipid-based NPs, and metal NPs. Poly(ethylene glycol) chains were commonly incorporated into NP compositions, enhancing their biocompatibility and circulation time. Targeting moieties such as folic acid and hyaluronic acid further augmented the specificity of drug delivery to breast cancer cells. Experimental design varied among studies, encompassing different animal models, routes of administration, and treatment durations. Intravenous administration emerged as the predominant route, although alternative routes such as intraperitoneal and intratumoral administration were also explored. The onset of treatment protocols varied based on days after tumour induction or tumour volume, with curcumin doses ranging from 2 to 100 mg/kg and administered with varying frequencies. In conclusion, Cur-NPs represent a promising therapeutic approach for breast cancer treatment, offering enhanced efficacy and safety profiles compared to free curcumin. Further research is warranted to optimize Cur-NP formulations and elucidate their clinical potential in breast cancer patients. The review also identified a diverse array of nanoparticle formulations employed in breast cancer therapy, including liposomes, polymeric nanoparticles, micelles, and dendrimers. These nanoparticles were engineered to encapsulate various anticancer drugs, including chemotherapeutic agents, molecularly targeted therapies, and immunomodulators, with the aim of enhancing their efficacy and reducing systemic toxicity. Targeted drug delivery strategies were employed to selectively deliver therapeutic agents to tumour cells while sparing healthy tissues, thereby minimizing off-target effects and improving treatment outcomes. Preclinical studies provided compelling evidence of the efficacy of nanoparticle-based therapies in inhibiting tumour growth, suppressing metastasis, and overcoming drug resistance in breast cancer models. Nanoparticles demonstrated superior pharmacokinetic properties, enhanced bioavailability, and controlled drug release kinetics, leading to improved therapeutic efficacy compared to conventional formulations. Furthermore, nanoparticle-based therapies exhibited synergistic effects when combined with traditional chemotherapy agents, leading to enhanced antitumor activity and reduced treatment resistance. Clinical studies evaluating the safety and efficacy of nanoparticle-based therapies in breast cancer patients demonstrated promising results, with favourable tolerability profiles and encouraging preliminary efficacy outcomes. However, challenges remain in translating preclinical findings into clinical practice, including issues related to scalability, manufacturing, and regulatory approval. Additionally, further research is needed to optimize nanoparticle formulations, tailor treatment strategies to individual patient profiles, and elucidate long-term safety and efficacy outcomes.

Design and evaluation of magnetic-targeted bilosomal gel for rheumatoid arthritis: flurbiprofen delivery using superparamagnetic iron oxide nanoparticles.

The study aimed to systematically enhance the fabrication process of flurbiprofen-loaded bilosomes (FSB) using Quality by Design (QbD) principles and Design of Experiments (DOE). The objective was to develop an optimized formulation with improved entrapment efficiency and targeted drug delivery capabilities. The optimization process involved applying QbD principles and DOE to achieve the desired formulation characteristics. Superparamagnetic iron oxide nanoparticles (SPIONs) were incorporated to impart magnetic responsiveness. The size, entrapment efficiency, morphology, and in vitro release patterns of the FSB formulation were evaluated. Additionally, an in situ forming hydrogel incorporating FSB was developed, with its gelation time and drug release kinetics assessed. In vivo studies were conducted on osteoarthritic rats to evaluate the efficacy of the FSB-loaded hydrogel. The optimized FSB formulation yielded particles with a size of 453.60nm and an entrapment efficiency of 91.57%. The incorporation of SPIONs enhanced magnetic responsiveness. Morphological evaluations and in vitro release studies confirmed the structural integrity and sustained release characteristics of the FSB formulation. The in situ forming hydrogel exhibited a rapid gelation time of approximately 40 ± 1.8s and controlled drug release kinetics. In vivo studies demonstrated a 27.83% reduction in joint inflammation and an 85% improvement in locomotor activity in osteoarthritic rats treated with FSB-loaded hydrogel. This comprehensive investigation highlights the potential of FSB as a promising targeted drug delivery system for the effective management of osteoarthritis. The use of QbD and DOE in the formulation process, along with the integration of SPIONs, resulted in an optimized FSB formulation with enhanced entrapment efficiency and targeted delivery capabilities. The in situ forming hydrogel further supported the formulation's applicability for injectable applications, providing rapid gelation and sustained drug release. The in vivo results corroborate the formulation's efficacy, underscoring its potential for improving the treatment of osteoarthritis.

Intranasal Administration of Bedaquiline-Loaded Fucosylated Liposomes Provides Anti-Tubercular Activity while Reducing the Potential for Systemic Side Effects.

Liposomal formulations of antibiotics for inhalation offer the potential for the delivery of high drug doses, controlled drug release kinetics in the lung, and an excellent safety profile. In this study, we evaluated the in vivo performance of a liposomal formulation for the poorly soluble, antituberculosis agent, bedaquiline. Bedaquiline was encapsulated within monodisperse liposomes of ∼70 nm at a relatively high drug concentration (∼3.6 mg/mL). Formulations with or without fucose residues, which bind to C-type lectin receptors and mediate a preferential binding to macrophage mannose receptor, were prepared, and efficacy was assessed in an in vivo C3HeB/FeJ mouse model of tuberculosis infection (H37Rv strain). Seven intranasal instillations of 5 mg/kg bedaquiline formulations administered every second day resulted in a significant reduction in lung burden (∼0.4-0.6 Δlog10 CFU), although no differences between fucosylated and nonfucosylated formulations were observed. A pharmacokinetic study in healthy, noninfected Balb/c mice demonstrated that intranasal administration of a single dose of 2.5 mg/kg bedaquiline liposomal formulation (fucosylated) improved the lung bioavailability 6-fold compared to intravenous administration of the same formulation at the same dose. Importantly, intranasal administration reduced systemic concentrations of the primary metabolite, N-desmethyl-bedaquiline (M2), compared with both intravenous and oral administration. This is a clinically relevant finding as the M2 metabolite is associated with a higher risk of QT-prolongation in predisposed patients. The results clearly demonstrate that a bedaquiline liposomal inhalation suspension may show enhanced antitubercular activity in the lung while reducing systemic side effects, thus meriting further nonclinical investigation.

Scaffold-Mediated Drug Delivery for Enhanced Wound Healing: A Review.

Wound healing is a complex physiological process involving coordinated cellular and molecular events aimed at restoring tissue integrity. Acute wounds typically progress through the sequential phases of hemostasis, inflammation, proliferation, and remodeling, while chronic wounds, such as venous leg ulcers and diabetic foot ulcers, often exhibit prolonged inflammation and impaired healing. Traditional wound dressings, while widely used, have limitations such poor moisture retention and biocompatibility. To address these challenges and improve patient outcomes, scaffold-mediated delivery systems have emerged as innovative approaches. They offer advantages in creating a conducive environment for wound healing by facilitating controlled and localized drug delivery. The manuscript explores scaffold-mediated delivery systems for wound healing applications, detailing the use of natural and synthetic polymers in scaffold fabrication. Additionally, various fabrication techniques are discussed for their potential in creating scaffolds with controlled drug release kinetics. Through a synthesis of experimental findings and current literature, this manuscript elucidates the promising potential of scaffold-mediated drug delivery in improving therapeutic outcomes and advancing wound care practices.

Polymeric nanoparticles – a review

Polymeric nanoparticles have emerged as versatile and promising platforms in the field of nanotechnology, offering unique properties and functionalities for various applications. These nanoparticles, typically ranging from 1 to 1000 nanometers in size, are composed of biocompatible or biodegradable polymers, offering controlled drug delivery, imaging capabilities, and targeted therapy. This abstract provides an overview of the synthesis methods, characterization techniques, and applications of polymeric nanoparticles in drug delivery, gene therapy, diagnostics, and imaging. Various polymeric materials, including synthetic and natural polymers, are explored for their suitability in nanoparticle formulations. The choice of polymers influences crucial properties such as biocompatibility, biodegradability, and controlled drug release kinetics, enhancing the therapeutic efficacy and reducing side effects. The ability to encapsulate a diverse range of payloads, including hydrophobic and hydrophilic compounds, makes polymeric nanoparticles highly adaptable for different applications.

Multi-vesicular Liposome and its Applications: A Novel Chemically Modified Approach for Drug Delivery Application.

This study aimed to elaborate on all the aspects of multivesicular liposomes, including structure, function, topology, etc. Liposomes are a unique drug delivery system, in which both hydrophilic and hydrophobic drug molecules can be incorporated. Particularly, multivesicular liposomes have more advantages than other liposomes because of their unique structure. This study provides an overview of several works already performed by various researchers in this field. Numerous studies have reported on preparing and evaluating multivesicular liposomes for drug delivery applications. This study summarizes the process of formulating multivesicular liposomes and their application in drug delivery systems and provides details about how to resolve the problem of limited solubility and stability of biomolecules, along with controlled drug release kinetics, with the possibility of loading various drugs. There is no doubt that multivesicular liposome opens new avenues to develop novel drug delivery system for achieving the desired functional performances and expanding the applications in the drug delivery area.

Development and characterization of Tinospora cordifolia extract-loaded SLNs for the treatment of autoimmune hepatitis

Solid Lipid Nanoparticles (SLNs) have emerged as promising drug delivery systems with the potential to enhance the therapeutic efficacy of bioactive compounds. In this study, T. Cordifolia extract-loaded SLNs were developed and characterized for their application in the treatment of autoimmune hepatitis. T. Cordifolia, known for its immunomodulatory and anti-inflammatory properties, was chosen as the active ingredient. The formulations were systematically evaluated for drug-excipient compatibility, particle size, zeta potential, drug loading efficiency, drug release kinetics, encapsulation efficiency, in-vitro release, and stability. The results indicated "No Change" in drug-excipient compatibility, ensuring the formulation's stability. The SLNs exhibited nanoscale particle sizes (159.30 nm to 172.12 nm) with narrow size distributions, facilitating consistent drug delivery. Negative zeta potentials (-28.28 mV to -35.44 mV) indicated colloidal stability. High drug loading efficiencies (up to 32.23%) and controlled drug release kinetics were observed, suggesting the potential for sustained and targeted drug delivery. Encapsulation efficiencies of up to 83.41% highlighted efficient drug loading within the SLNs. In-vitro release studies revealed that SLN2 and SLN4 exhibited superior drug release profiles compared to other formulations. These findings indicate the potential of these formulations for controlled drug delivery. In-vivo efficacy studies in murine models of autoimmune hepatitis are recommended to assess the therapeutic benefits of T. Cordifolia extract-loaded SLNs. Additionally, stability studies demonstrated the maintenance of critical parameters, such as particle size, zeta potential, and drug loading efficiency, under different storage conditions.

Investigation of controlled drug release of ibuprofen with prepared and characterized innovative bigel materials

AbstractNew systems called bigels have been discovered recently, alongside other consolidations of hydrogels and organogels. The purpose of this research is to develop bigels using span 40, alginate, centaury oil, black cumin oil and sorbitan monopalmitate for controlled ibuprofen release. Characterization of prepared materials was performed using various analysis by fourier transform infrared spectroscopy and differential scanning calorimetry. The pH 7.2 level was used for the swelling test of bigels. Cytocompatibility of bigels was determined by using human immortalized human keratinocyte cells. Bigels have been tested for their effectiveness as controlled medication delivery formulations by in vitro studies. The prepared bigels did not show any toxic effects on human cells. This indicates that the prepared materials were biocompatible. For controlled drug release kinetics, zeroth‐order, first‐order, Higuchi, and Korsmeyer‐Peppas kinetic models were used. According to results, the kinetic modeling of bigels by Korsmeyer‐Peppas is also highly compatible. Consequently, controlled drug release was successfully carried out by the novel bigel materials formed by adding an active ingredient. Our results clearly indicate that bigels have been an alternative potential material for controlled drug delivery systems by the properties of biocompatibility, slower release of the drug and the diffusion release mechanism.

Synthesis of Quercetin-Loaded Silver Nanoparticles and Assessing Their Anti-Bacterial Potential.

The study delves into the multifaceted potential of quercetin (Qu), a phytoconstituent found in various fruits, vegetables, and medicinal plants, in combination with silver nanoparticles (AgNPs). The research explores the synthesis and characterization of AgNPs loaded with Qu and investigates their pharmaceutical applications, particularly focusing on antibacterial properties. The study meticulously evaluates Qu's identity, and physicochemical properties, reaffirming its suitability for pharmaceutical use. The development of Qu-loaded AgNPs demonstrates their high drug entrapment efficiency, ideal particle characteristics, and controlled drug release kinetics, suggesting enhanced therapeutic efficacy and reduced side effects. Furthermore, the research examines the antibacterial activity of Qu in different solvents, revealing distinct outcomes. Qu, both in methanol and water formulations, exhibits antibacterial activity against Escherichia coli, with the methanol formulation displaying a slightly stronger efficacy. In conclusion, this study successfully synthesizes AgNPs loaded with Qu and highlights their potential as a potent antibacterial formulation. The findings underscore the influence of solvent choice on Qu's antibacterial properties and pave the way for further research and development in drug delivery systems and antimicrobial agents. This innovative approach holds promise for addressing microbial resistance and advancing pharmaceutical formulations for improved therapeutic outcomes.

The Promise of Exosomes as Drug Delivery Systems

Exosomes are small extracellular vesicles that play a role in cell-to-cell communication by transferring bioactive molecules such as proteins, nucleic acids, and lipids between cells. Over the past few years, there have been significant advances in utilizing exosomes as drug delivery systems due to their unique properties, including their ability to target specific cells and tissues. Especially advances in targeted delivery, nanoparticle incorporation, personalized medicine, cargo delivery, imaging, and tracking have excited the pharmaceutical community about their potential use in these areas. I briefly discuss the significance of exosomes in these areas or research interests. Natural Cargo Delivery: Exosomes naturally transport a variety of biomolecules, making them attractive vehicles for delivering drugs, nucleic acids (such as siRNA and miRNA), proteins, and even small molecules. Researchers are harnessing this inherent cargo delivery capability to load exosomes with therapeutic agents. Engineered Exosomes: Scientists are engineering exosomes to enhance their drug delivery capabilities. This includes modifying the surface of exosomes to display targeting ligands that can direct them to specific cell types or tissues, improving their stability, and optimizing their cargo-loading efficiency. Targeted Delivery: One of the key advantages of using exosomes for drug delivery is their potential for targeted delivery. By engineering exosomes to carry targeting molecules on their surface, researchers can selectively deliver therapeutic agents to specific cells or disease sites, minimizing off-target effects. Personalized Medicine: Exosomes can be isolated from a patient's cells (autologous exosomes), loaded with personalized therapies, and then re-administered to the patient. This personalized approach holds promise for tailoring treatments to individual patients' needs. Imaging and Tracking: Exosomes can be labeled with imaging agents to track their distribution and uptake in vivo. This information is crucial for understanding the pharmacokinetics and biodistribution of exosome-based drug delivery systems. Nanoparticle Incorporation: Exosomes can be loaded with nanoparticles, such as liposomes or polymer-based carriers, to increase their cargo capacity and control drug release kinetics. This combination allows for synergistic benefits of both exosome-mediated and nanoparticle-based drug delivery. Clinical Translation: Clinical trials involving exosome-based therapies are underway for various diseases, including cancer and neurodegenerative disorders. These trials provide valuable insights into the safety, efficacy, and challenges associated with exosome-based drug delivery in humans. Regulatory Considerations: The field of exosome-based drug delivery is also evolving in terms of regulatory considerations. Regulatory agencies are working to establish guidelines and standards for developing and approving exosome-based therapies. Exosome Isolation and Purification Techniques: Advances in exosome isolation and purification methods are critical for obtaining high-quality and consistent exosome preparations for drug delivery studies. Improved techniques contribute to the reproducibility and reliability of exosome-based therapies. Disease-Specific Cargo: Exosomes derived from specific cell types or disease models can be isolated and used as delivery vehicles for disease-specific cargo, including diagnostic biomarkers and therapeutic agents. This enables precise delivery to disease-affected cells. Combination Therapies: Researchers are exploring the potential of using exosomes to deliver combination therapies, where multiple therapeutic agents are loaded into a single exosome to achieve synergistic effects. The study of exosomes as drug delivery systems is rapidly advancing and holds great promise for improving the targeted delivery of therapeutic agents, reducing side effects, and enabling personalized medicine approaches. However, scalability, cargo loading efficiency, safety, and regulatory approval challenges still need to be addressed as the field progresses.

Profiling target engagement and cellular uptake of cRGD-decorated clinical-stage core-crosslinked polymeric micelles

Polymeric micelles are increasingly explored for tumor-targeted drug delivery. CriPec® technology enables the generation of core‐crosslinked polymeric micelles (CCPMs) based on thermosensitive (mPEG-b-pHPMAmLacn) block copolymers, with high drug loading capacity, tailorable size, and controlled drug release kinetics. In this study, we decorated clinical-stage CCPM with the αvβ3 integrin-targeted cyclic arginine-glycine-aspartic acid (cRGD) peptide, which is one of the most well-known active targeting ligands evaluated preclinically and clinically. Using a panel of cell lines with different expression levels of the αvβ3 integrin receptor and exploring both static and dynamic incubation conditions, we studied the benefit of decorating CCPM with different densities of cRGD. We show that incubation time and temperature, as well as the expression levels of αvβ3 integrin by target cells, positively influence cRGD-CCPM uptake, as demonstated by immunofluorescence staining and fluorescence microscopy. We demonstrate that even very low decoration densities (i.e., 1 mol % cRGD) result in increased engagement and uptake by target cells as compared to peptide-free control CCPM, and that high cRGD decoration densities do not result in a proportional increase in internalization. In this context, it should be kept in mind that a more extensive presence of targeting ligands on the surface of nanomedicines may affect their pharmacokinetic and biodistribution profile. Thus, we suggest a relatively low cRGD decoration density as most suitable for in vivo application.Graphical

Phenylboronic acid modified hydrogel materials and their potential for use in contact lens based drug delivery

The use of hydrogel-based contact lens materials holds promise for ophthalmic drug delivery by increasing drug residence time, improving drug bioavailability, reducing administration frequency, and enhancing special site targeting. Issues such as ease of manufacturing, lens comfort and appropriate release kinetics must be considered. Furthermore, the high water content of hydrogel materials can result in rapid and poorly controlled release kinetics. Herein, we modified common hydrogels used in contact lens manufacturing with phenylboronic acid (PBA). PBA addresses these material design issues since boronate esters are easily formed when boron acid and diols interact, opening up a pathway for simple modification of the model lens materials with saccharide based wetting agents. The wetting agents have the potential to improve lens comfort. Furthermore, the hydrophobicity of PBA and the presence of diols can be useful to help control drug release kinetics. In this work, polymerizable 3-(acrylamido)phenylboronic acid (APBA) was synthesized and incorporated into various hydrogels used in contact lens applications, including poly(2-hydroxyethylmethacrylate) (PHEMA), polyvinylpyrrolidone (PVP) and poly(N,N-dimethyl acrylamide) (PDMA) using UV induced free radical polymerization. The APBA structure and its incorporation into the hydrogel materials were confirmed by NMR and FTIR. The materials were shown to interact with and bind wetting agents such as hyaluronan (HA) and hydroxypropyl guar (HPG) by simple soaking in an aqueous solution. The equilibrium water content of the modified materials was characterized, demonstrating that most materials are still in the appropriate range after the introduction of the hydrophobic PBA. The release of three model ophthalmic drugs with varying hydrophilicity, atropine, atropine sulfate and dexamethasone, was examined. The presence of PBA in the materials was found to promote sustained drug release due to its hydrophobic nature. The results suggest that the modification of the materials with PBA was able to not only provide a mucoadhesive property that enhanced wetting agent interactions with the materials, but had the potential to alter drug release. Thus, the modification of contact lens materials with mucoadhesive functionality may be useful in the design of hydrogel contact lenses for ophthalmic drug release and wetting agent binding.

Functional drug carriers formed by RGD-modified β-CD-HPG for the delivery of docetaxel for targeted inhibition of nasopharyngeal carcinoma cells.

In this study, a drug delivery system was prepared by grafting the targeting molecule arginine-glycine-aspartic acid (RGD) onto hyperbranched polyglycerol (HPG)-modified β-cyclodextrin (β-CD-HPG) for the targeted inhibition of nasopharyngeal carcinoma (NPC) cells. The obtained β-CD-HPG-RGD with a relatively small size and low surface charge delivered docetaxel (Doc) effectively and displayed a targeting effect to human NPC HNE-1 cells, as confirmed by confocal laser scanning microscopy and flow cytometry. The in vitro drug release analysis exhibited the controlled drug release kinetics of the β-CD-HPG-RGD/Doc nanomedicine. β-CD-HPG-RGD/Doc effectively inhibited the proliferation of HNE-1 cells and promoted apoptosis. Moreover, its biocompatibility in vitro and in vivo was assessed. The results indicate that the β-CD-HPG-RGD/Doc nanomedicine has potential application in NPC targeting therapy.

Drug Release Kinetics from Nondegradable Hydrophobic Polymers Can Be Modulated and Predicted by the Glass Transition Temperature.

Controlling drug release kinetics within a desired therapeutic window is the central task when designing polymeric drug delivery systems. Complex polymer chemistries have often been explored to control water penetration, polymer degradation rate, or the mesh network size of delivery systems. Here, a simple parameter for controlling the release rate and duration of nondegradable hydrophobic polymers is discovered. A systematic study involving 59 polymers and multiple drugs demonstrates that the glass transition temperature, Tg , is a critical factor that dictates drug release kinetics from nondegradable hydrophobic polymers. Drug release rate exhibits a unique and simple linear correlation of (T - Tg )0.5 despite variability of polymer structure and type. An empirical model established based on the special correlation can accurately simulate and predict drug release kinetics from polymers saving substantial time typically required to test long-acting drug delivery systems.