Sustained Drug Delivery Research Articles

Next-Generation Nanomedicine Approaches for the Management of Retinal Diseases.

Retinal diseases are one of the leading causes of blindness globally. The mainstay treatments for these blinding diseases are laser photocoagulation, vitrectomy, and repeated intravitreal injections of anti-vascular endothelial growth factor (VEGF) or steroids. Unfortunately, these therapies are associated with ocular complications like inflammation, elevated intraocular pressure, retinal detachment, endophthalmitis, and vitreous hemorrhage. Recent advances in nanomedicine seek to curtail these limitations, overcoming ocular barriers by developing non-invasive or minimally invasive delivery modalities. These modalities include delivering therapeutics to specific cellular targets in the retina, providing sustained delivery of drugs to avoid repeated intravitreal injections, and acting as a scaffold for neural tissue regeneration. These next-generation nanomedicine approaches could potentially revolutionize the treatment landscape of retinal diseases. This review describes the availability and limitations of current treatment strategies and highlights insights into the advancement of future approaches using next-generation nanomedicines to manage retinal diseases.

Microfluidic-Assisted Synthesis of Metal-Organic Framework -Alginate Micro-Particles for Sustained Drug Delivery.

Drug delivery systems (DDS) are continuously being explored since humans are facing more numerous complicated diseases than ever before. These systems can preserve the drug's functionality and improve its efficacy until the drug is delivered to a specific site within the body. One of the least used materials for this purpose are metal-organic frameworks (MOFs). MOFs possess many properties, including their high surface area and the possibility for the addition of functional surface moieties, that make them ideal drug delivery vehicles. Such properties can be further improved by combining different materials (such as metals or ligands) and utilizing various synthesis techniques. In this work, the microfluidic technique is used to synthesize Zeolitic Imidazole Framework-67 (ZIF-67) containing cobalt ions as well as its bimetallic variant with cobalt and zinc as ZnZIF-67 to be subsequently loaded with diclofenac sodium and incorporated into sodium alginate beads for sustained drug delivery. This study shows the utilization of a microfluidic approach to synthesize MOF variants. Furthermore, these MOFs were incorporated into a biopolymer (sodium alginate) to produce a reliable DDS which can perform sustained drug releases for up to 6 days (for 90% of the full amount released), whereas MOFs without the biopolymer showed sudden release within the first day.

Villi Inspired Mechanical Interlocking for Intestinal Retentive Devices.

Intestinal retentive devices have applications ranging from sustained oral drug delivery systems to indwelling ingestible medical devices. Current strategies to retain devices in the small intestine primarily focus on chemical anchoring using mucoadhesives or mechanical coupling using expandable devices or structures that pierce the intestinal epithelium. Here, the feasibility of intestinal retention using devices containing villi-inspired structures that mechanically interlock with natural villi of the small intestine is evaluated. First the viability of mechanical interlocking as an intestinal retention strategy is estimated by estimating the resistance to peristaltic shear between simulated natural villi and devices with various micropost geometries and parameters. Simulations are validated in vitro by fabricating micropost array patches via multistep replica molding and performing lap-shear tests to evaluate the interlocking performance of the fabricated microposts with artificial villi. Finally, the optimal material and design parameters of the patches that can successfully achieve retention in vivo are predicted. This study represents a proof-of-concept for the viability of micropost-villi mechanical interlocking strategy to develop nonpenetrative multifunctional intestinal retentive devices for the future.

Mycobacterial lipid-derived immunomodulatory drug- liposome conjugate eradicates endosome-localized mycobacteria

Tuberculosis is a challenging disease due to the intracellular residence of its pathogen, Mycobacterium tuberculosis, and modulation of the host bactericidal responses. Lipids from Mycobacterium tuberculosis regulate macrophage immune responses dependent on the infection stage and intracellular location. We show that liposomes constituted with immunostimulatory lipids from mycobacteria modulate the cellular immune response and synergize with sustained drug delivery for effective pathogen eradication. We evaluate the pH-dependent release of Rifampicin from the mycobacterial-lipid-derived liposomes intracellularly and in vitro, their cell viability, long-term stability, and antimicrobial efficacy. Intracellular drug levels were higher following liposome treatment compared with the free drug in a temporal fashion underlying a sustained release. The drug-encapsulated liposomes were taken up by clathrin-mediated endocytosis and elicited a robust pro-inflammatory immune response while localizing in the recycling and late endosomes. Notably, these were the same cellular compartments that contained the pathogen underlying localized intracellular targeting. Our results also imply a lipid-centric and species-specific selectivity of the liposomal drug formulations. This work provides a proof-of-concept for the dual-action of liposomes derived from the pathogen itself for their effective eradication, in conjunction with the attuned host immunomodulation.

Evaluation of covalent and supra-molecular interactions in phosphated galacturonic-glucuronic acid for network structure for use in wound dressings

Keeping in view the wound healing properties of sterculia gum (SG) and ceftriaxone in consideration, in the present work, antibiotic drug encapsulated SG and poly(vinylphosphonic acid) [poly(VPA)] based copolymeric hydrogel wound dressings were designed to enhance the wound healing. Copolymers were characterized by FESEM & EDS, AFM, FTIR, 13C NMR, XRD, TGA and biomedical assay of blood compatibility, mucoadhesion and antioxidant properties. AFM analysis revealed 76.5 nm average roughness and XRD analysis showed sharp peaks at 2θ = 21°. FTIR spectrum of copolymer indicated characteristic peaks at 1116 cm−1 due to stretching vibration of P = O groups of poly(VPA) and twin peaks at 985 and 920 cm−1 due to asymmetric and symmetric vibration of P-O respectively and depicted grafting of phosphated polymers onto gum. The hemolysis test (hemolysis index = 3.40 ± 0.18%) revealed biocompatible nature and the adhesion test demonstrated 84 ± 5.00 mN detachment force which was required to detach the copolymer from the mucosal membrane. Hydrogel dressings absorbed 6.0 ± 5.00 (g/g gel) simulated wound fluid to main the moist wound environment. They were found permeable to O2 and impermeable to microbes and also exhibited antioxidant character. The release profile of ceftriaxone elucidated sustained release of encapsulated ceftriaxone drug with non-Fickian diffusion mechanism and was best fitted in first order kinetic model. Covalent and supra-molecular interactions formed in phosphated galacturonic-glucuronic acid of sterculia gum (SG) were found useful for sustained drug delivery and mucoadhesive properties. These biophysical interactions demonstrated the suitability of antibiotic-encapsulated network structures for wound dressing applications.

Glioblastoma-targeted, local and sustained drug delivery system based on an unconventional lipid nanocapsule hydrogel

The objective of this work was to develop an implantable therapeutic hydrogel that will ensure continuity in treatment between surgery and radiochemotherapy for patients with glioblastoma (GBM). A hydrogel of self-associated gemcitabine-loaded lipid nanocapsules (LNC) has shown therapeutic efficacy in vivo in murine GBM resection models. To improve the targeting of GBM cells, the NFL-TBS.40–63 peptide (NFL), was associated with LNC. The LNC-based hydrogels were formulated with the NFL. The peptide was totally and instantaneously adsorbed at the LNC surface, without modifying the hydrogel mechanical properties, and remained adsorbed to the LNC surface after the hydrogel dissolution. In vitro studies on GBM cell lines showed a faster internalization of the LNC and enhanced cytotoxicity, in the presence of NFL. Finally, in vivo studies in the murine GBM resection model proved that the gemcitabine-loaded LNC with adsorbed NFL could target the non-resected GBM cells and significantly delay or even inhibit the apparition of recurrences.

LIPUS-S/B@NPs regulates the release of SDF-1 and BMP-2 to promote stem cell recruitment-osteogenesis for periodontal bone regeneration.

Purpose: Poly (lactic-co-glycolic acid)-based nanoparticles (PLGA NPs) have been widely used as the carrier for sustainable drug delivery. However, the drug release from the NPs was usually incomplete and uncontrollable. Herein, a low intensity pulsed ultrasound (LIPUS) assisted SDF-1/BMP-2@nanoparticles (S/B@NPs) system was fabricated to facilitate stem cell recruitment-osteogenesis for periodontal bone regeneration. Methods: In this work, S/B@NPs were prepared with double-emulsion synthesis method. Then the S/B release profile from NPs was evaluated with or without low intensity pulsed ultrasound treatment. Afterwards, the stem cell recruiting and osteoinductive capacities of LIPUS-S/B@NPs were detected with human periodontal ligament cells (hPDLCs) in vitro and in a rat periodontal bone defect model. Results: The results indicated that S/B@NPs were successfully prepared and LIPUS could effectively regulate the release of S/B and increase their final releasing amount. Moreover, LIPUS-S/B@NPs system significantly promoted hPDLCs migrating and osteogenesis in vitro and recruiting rBMSCs to the rat periodontal defect and facilitated bone regeneration in vivo. Conclusion: Our LIPUS assisted S/B@NPs system can effectively facilitate stem cell recruitment and periodontal bone regeneration. Considering its reliable safety and therapeutic effect on bone fracture, LIPUS, as an adjuvant therapy, holds great potential in the regulation of drug delivery systems for bone healing.

Innovative Strategies for Drug Delivery to the Ocular Posterior Segment.

Innovative and new drug delivery systems (DDSs) have recently been developed to vehicle treatments and drugs to the ocular posterior segment and the retina. New formulations and technological developments, such as nanotechnology, novel matrices, and non-traditional treatment strategies, open new perspectives in this field. The aim of this mini-review is to highlight promising strategies reported in the current literature based on innovative routes to overcome the anatomical and physiological barriers of the vitreoretinal structures. The paper also describes the challenges in finding appropriate and pertinent treatments that provide safety and efficacy and the problems related to patient compliance, acceptability, effectiveness, and sustained drug delivery. The clinical application of these experimental approaches can help pave the way for standardizing the use of DDSs in developing enhanced treatment strategies and personalized therapeutic options for ocular pathologies.

Local Sustained Chemotherapy of Pancreatic Cancer Using Endoscopic Ultrasound-Guided Injection of Biodegradable Thermo-Sensitive Hydrogel.

Endoscopic ultrasound-guided fine-needle injection (EUS-FNI) offers a promising minimally invasive approach for locally targeted management of advanced pancreatic cancer. However, the efficacy is limited due to the rapid plasma clearance of chemotherapeutic agents. Injectable hydrogels can form drug release depots, which provide a feasible solution for optimizing targeted chemotherapy through EUS-FNI. A drug delivery system was developed, consisting of gemcitabine (GEM) and thermo-sensitive hydrogel (PLGA-PEG-PLGA, PPP). The injectability, gel formation ability, biocompatibility and sustained drug delivery properties of PPP hydrogel were verified in vitro and in vivo. The effects of GEM/PPP hydrogel on cell proliferation, invasion, metastasis, and apoptosis were explored through co-culturing with PANC-1 cells. The therapeutic effects of GEM/PPP hydrogel on xenograft mice were compared with those of GEM, ethanol and polidocanol using the precisely targeted EUS-FNI technology. Tumor sections were examined by H&E, Ki-67, and TUNEL staining. GEM/PPP hydrogel exhibited excellent injectability, biocompatibility, and the capability of sustained drug delivery for up to 7 days by forming a gel triggered by body temperature. It demonstrated the best therapeutic effects, significantly reducing proliferation, invasion and migration of PANC-1 cells while promoting apoptosis. After precise injection using EUS-FNI technology, GEM/PPP hydrogel resulted in a reduction of tumor weight by up to 75.96% and extending the survival period by 14.4 days with negligible adverse effects. Pathological examination revealed no systemic toxicity and significant apoptosis and minimal proliferation as well. The combination of GEM/PPP hydrogel and EUS-FNI technology provides an optimal approach of precise chemotherapy for pancreatic cancer, builds a bridge for clinical translation of basic research, and brings great hope for innovation of minimally invasive treatment modalities. The first-hand EUS image data obtained in this study also serves as a crucial reference for future clinical trials.

Intraocular Pressure and Eyedrop Usage Reduction with Intracameral Bimatoprost Implant.

Purpose: Sustained intraocular drug delivery devices are being developed to lower intraocular pressure (IOP) and improve adherence in patients with glaucoma. The purpose of this study was to assess the IOP and eyedrop usage reduction effects of intracameral bimatoprost implants. Methods: We retrospectively reviewed the records of 46 eyes from 38 patients who received an intracameral implant containing 10 μg of bimatoprost as a replacement or addition to their existing eyedrop regimen and investigated IOP, eyedrop usage, and adverse effects. Results: Patients were followed for an average of 274 ± 104 (mean ± standard deviation) days after implant. Mean reduction in IOP (mmHg) at 3 months ±30 days, 6 months ±60 days, and 12 months ±90 days postoperation compared to baseline was 1.26 ± 2.53 (P = 0.002), 0.93 ± 4.71 (P = 0.098), and 1.35 ± 5.24 (P = 0.053), respectively. Reduction in eyedrops at 3 months ±30 days, 6 months ±60 days, and 12 months ±90 days postoperation compared to baseline were 0.62 ± 0.49 (P < 0.001), 0.55 ± 0.73 (P < 0.001), and 0.51 ± 0.71 (P < 0.001), respectively. Fifteen eyes (32.6%) experienced implant failure, defined as either restarting IOP-lowering eyedrops or undergoing surgical intervention, at an average of 260 ± 122 days after implant. Conclusions: While some patients eventually experienced implant failure, intracameral bimatoprost implants may result in fewer adverse reactions and successfully lower IOP and eyedrop burden over a longer period than previously reported.

μMESH-Enabled Sustained Delivery of Molecular and Nanoformulated Drugs for Glioblastoma Treatment.

Modest tissue penetrance, nonuniform distribution, and suboptimal release of drugs limit the potential of intracranial therapies against glioblastoma. Here, a conformable polymeric implant, μMESH, is realized by intercalating a micronetwork of 3 × 5 μm poly(lactic-co-glycolic acid) (PLGA) edges over arrays of 20 × 20 μm polyvinyl alcohol (PVA) pillars for the sustained delivery of potent chemotherapeutic molecules, docetaxel (DTXL) and paclitaxel (PTXL). Four different μMESH configurations were engineered by encapsulating DTXL or PTXL within the PLGA micronetwork and nanoformulated DTXL (nanoDTXL) or PTXL (nanoPTXL) within the PVA microlayer. All four μMESH configurations provided sustained drug release for at least 150 days. However, while a burst release of up to 80% of nanoPTXL/nanoDTXL was documented within the first 4 days, molecular DTXL and PTXL were released more slowly from μMESH. Upon incubation with U87-MG cell spheroids, DTXL-μMESH was associated with the lowest lethal drug dose, followed by nanoDTXL-μMESH, PTXL-μMESH, and nanoPTXL-μMESH. In orthotopic models of glioblastoma, μMESH was peritumorally deposited at 15 days post-cell inoculation and tumor proliferation was monitored via bioluminescence imaging. The overall animal survival increased from ∼30 days of the untreated controls to 75 days for nanoPTXL-μMESH and 90 days for PTXL-μMESH. For the DTXL groups, the overall survival could not be defined as 80% and 60% of the animals treated with DTXL-μMESH and nanoDTXL-μMESH were still alive at 90 days, respectively. These results suggest that the sustained delivery of potent drugs properly encapsulated in conformable polymeric implants could halt the proliferation of aggressive brain tumors.

Nanotechnology-based Approaches for the Treatment of Toxocariasis: A Prospective Review

Toxocariasis, caused by Toxocara parasites, is a prevalent parasitic disease affecting millions of people worldwide. Conventional anthelmintic drugs for toxocariasis face challenges such as limited efficacy and potential adverse effects, necessitating exploring alternative therapeutic strategies. Nanotechnology has emerged as a promising approach for the treatment of toxocariasis. This prospective review provides an overview of the potential of nanotechnology in toxocariasis treatment and highlights critical advancements in the field. The current review aimed to provide an overview of toxocariasis and the current challenges in its treatment, such as limited efficacy and potential adverse effects. It emphasized the need for novel therapeutic approaches to overcome these limitations. The subsequent section focused on nanoparticle-based drug delivery systems, discussing the nanoparticles used in toxocariasis treatment, their advantages, and strategies for enhancing drug delivery efficiency. Nanotechnology in targeted therapy is a great strategy to treat toxocariasis. It explored targeting Toxocara parasites using nanoparticles, surface modifications for enhanced targeting, and controlled release and sustained drug delivery techniques. Nanodiagnostics and imaging techniques in diagnosing and monitoring provide promising futures for controlling toxocariasis. It explored the use of nanosensors for the sensitive detection of Toxocara parasites and various imaging modalities for parasite visualization. These advancements enabled timely intervention and personalized treatment strategies. Furthermore, the application of nanotechnology in vaccine development is fruitful for preventing toxocariasis. It highlights the use of nano vaccines for enhanced immune responses, controlled antigen delivery, and targeted immune cell activation. In conclusion, nanotechnology holds immense potential in the treatment of toxocariasis. Its unique features, such as targeted drug delivery, enhanced diagnostics, and improved vaccine efficacy, offer promising avenues for more effective and personalized approaches. Addressing evaluation, regulatory approval, cost-effectiveness, and scalability challenges is crucial for successful translation into clinical practice. The advancements in nanotechnology can potentially revolutionize toxocariasis treatment and improve patient outcomes.

Surface modification of graphene oxide by functionalized dendritic polyesters based on phthalic acid and pentaerythritol as a novel nanoplatform for sustained drug delivery: Statistical optimization using response surface methodology and release kinetics modelling

In this work, the third generation of polyester dendrimers was synthesized by conjugating phthalic acid and pentaerythritol on the graphene oxide surface. After the esterification reaction, 3, 5-dinitrobenzoyl chloride was grafted to the polyester dendrimer and used as a nanocarrier for the antibiotic-sustained delivery of the metronidazole. The success of the synthesis was confirmed by using various techniques. The batch sorption test was conducted according to the variables set by the central composite design under response surface methodology. The statistically optimized sorption efficiency (95.11%) was attained at pH= 5, 15 µg mL−1 concentration, and a contact time of 15 min. This data indicated that the pseudo-second-order kinetic and Langmuir isotherm models had greater correlation coefficients (R2) of 0.9980 and 0.9995, respectively than the other non-linear models. Based on the thermodynamic study such as ΔH°, ΔG°, and ΔS°, the adsorption efficiency of drug by nanoadsorbent was an endothermic (ΔH°= 16121.68 J mol−1), spontaneous process (ΔG° = −7.83 to 9.84 kJ mol−1), and entropy driven (ΔS° = 80.35 J mol−1K−1). Nearly 98.92% of the drug was released in simulated intestinal fluid, pH= 7.4, in 6 h and 34.96% in simulated gastric fluid, pH= 1.2, in 1 h. The nanocarrier had an encapsulation efficiency of 86.90% and a drug loading of 38.12%. The Korsmeyer-Peppas mathematical model adjusted well to the experimental drug release kinetic profile with non-Fickian diffusion (0.5 <n < 0.9 for all pH). The findings display that the synthesized nanocarrier could be a promising choice for the sustained delivery of metronidazole.

Injectable Hyaluronan-Based Thermoresponsive Hydrogels for Dermatological Applications.

Most marketed HA-based dermal fillers use chemical cross-linking to improve mechanical properties and extend their lifetime in vivo; however, stiffer products with higher elasticity require an increased extrusion force for injection in clinical practice. To balance longevity and injectability, we propose a thermosensitive dermal filler, injectable as a low viscosity fluid that undergoes gelation in situ upon injection. To this end, HA was conjugated via a linker to poly(N-isopropylacrylamide) (pNIPAM), a thermosensitive polymer using "green chemistry", with water as the solvent. HA-L-pNIPAM hydrogels showed a comparatively low viscosity (G' was 105.1 and 233 for Candidate1 and Belotero Volume®, respectively) at room temperature and spontaneously formed a stiffer gel with submicron structure at body temperature. Hydrogel formulations exhibited superior resistance against enzymatic and oxidative degradation and could be administered using a comparatively lower injection force (49 N and >100 N for Candidate 1 and Belotero Volume®, respectively) with a 32G needle. Formulations were biocompatible (viability of L929 mouse fibroblasts was >100% and ~85% for HA-L-pNIPAM hydrogel aqueous extract and their degradation product, respectively), and offered an extended residence time (up to 72 h) at the injection site. This property could potentially be exploited to develop sustained release drug delivery systems for the management of dermatologic and systemic disorders.

Aloe vera-Based Polymeric Network: A Promising Approach for Sustained Drug Delivery, Development, Characterization, and In Vitro Evaluation

The present study was conducted to fabricate and characterize mucilage-based polymeric networks of Aloe vera for controlled drug release. Aloe vera mucilage was used to develop a polymeric network via the free-radical polymerization method using potassium persulphate as the initiator, N′ N′-Methylene bisacrylamide as the crosslinker, and acrylamide as the monomer. Using varying concentrations of Aloe vera mucilage, crosslinker, and monomer, we developed different formulations. Swelling studies were conducted at pH 1.2 and 7.4. Concentrations of polymer, monomer, and crosslinker were optimized as a function of swelling. Porosity and gel content were calculated for all samples. FTIR, SEM, XRD, TGA, and DSC studies were conducted for the characterization of polymeric networks. Thiocolchicoside was used as a model drug to study the in vitro release in acidic and alkaline pH. Various kinetics models were applied by using a DD solver. Increasing content of monomer and crosslinker swelling, porosity, and drug release decreased while gel content increased. An increase in Aloe vera mucilage concentration promotes swelling, porosity, and drug release of the polymeric network but decreases gel content. The FTIR study confirmed the formation of crosslinked networks. SEM indicated that the polymeric network had a porous structure. DSC and XRD studies indicated the entrapment of drugs inside the polymeric networks in amorphous form. The analytical method was validated according to ICH guidelines in terms of linearity, range, LOD, LOQ, accuracy, precision, and robustness. Analysis of drug release mechanism revealed Fickian behavior of all formulations. All these results indicated that the M1 formulation was considered to be the best polymeric network formulation in terms of sustaining drug release patterns.

New trends towards glaucoma treatment: Topical osmoprotective microemulsions loaded with latanoprost

The chronic use of hypotensive agents eventually leads to ocular surface damage and poor patient compliance during glaucoma management. Thus, new sustained drug delivery systems are needed. This work aimed to develop osmoprotective latanoprost-loaded microemulsion formulations as new potential glaucoma treatments with ocular surface protective properties. The microemulsions were characterized and latanoprost encapsulation efficacy determined. In-vitro tolerance, osmoprotective efficacy, cell internalization as well as cell-microemulsion interactions and distribution were performed. In vivo hypotensive activity was conducted in rabbits to assess intraocular pressure reduction and relative ocular bioavailability. Physicochemical characterization showed nanodroplet sizes within 20–30 nm, being in vitro tolerance within 80 and 100% viability in corneal and conjunctival cells. Besides, microemulsions exhibited higher protection under hypertonic conditions than untreated cells. Cell fluorescence lasted for 11 days after short exposure to coumarin-loaded microemulsions (5 min) showing extensive internalization in different cell compartments by electronic microscopy. In vivo studies exhibited that a single instillation of latanoprost-loaded microemulsions reduced the intraocular pressure for several days (4–6 days without polymer and 9–13 days with polymers). Relative ocular bioavailability was 4.5 and 19 times higher than the marketed formulation. These findings suggest the use of these microemulsions as potential combined strategies for extended surface protection and glaucoma treatment.

Development of amylopectin based polyurethanes for sustained drug release studies

In this research work, the crosslinked structure of polyurethane has been exploited for sustained drug delivery. Polyurethane composites have been prepared by the reaction of isophorone diisocyanate (IPDI) and polycaprolactone diol (PCL), which were further extended by varying the mole ratios of amylopectin (AMP) and 1,4-butane diol (1,4-BDO) chain extenders. The progress and completion of the reaction of polyurethane (PU) were confirmed using Fourier Transform infrared (FTIR) and nuclear magnetic resonance (1H NMR) spectroscopic techniques. Gel permeation chromatography (GPC) analysis showed that the molecular weights of prepared polymers were increased with the addition of amylopectin into the PU matrix. The molecular weight of AS-4 (Mw ≈ 99,367) was found threefold as compared to amylopectin-free PU (Mw ≈ 37,968). Thermal degradation analysis was done using thermal gravimetric analysis (TGA) and inferred that AS-5 showed stability up to 600 °C which was the maximum among all PUs because AMP has a large number of –OH units for linking with prepolymer resulting in a more cross-linked structure which improved the thermal stability of the AS-5 sample. The samples prepared with AMP showed less drug release (<53 %) as compared to the PU sample prepared without AMP (AS-1).

Therapeutic applications of contact lens-based drug delivery systems in ophthalmic diseases

Traditional ophthalmic drugs, such as eye drops, gels and ointments, are accompanied by many problems, including low bioavailability and potential drug side effects. Innovative ophthalmic drug delivery systems have been proposed to overcome the limitations associated with traditional formulations. Recently, contact lens-based drug delivery systems have gained popularity owing to their advantages of sustained drug delivery, prolonged drug retention, improved bioavailability, and few drug side effects. Various methods have been successfully applied to drug-loaded contact lenses and prolonged the drug release time, such as chemical crosslinking, material embedding, molecular imprinting, colloidal nanoparticles, vitamin E modification, drug polymer film/coating, ion ligand polymerization systems, and supercritical fluid technology. Contact lens-based drug delivery systems play an important role in the treatment of multifarious ophthalmic diseases. This review discusses the latest developments in drug-loaded contact lenses for the treatment of ophthalmic diseases, including preparation methods, application in ophthalmic diseases and future prospects.

Nanocarriers for ocular drug delivery: Recent advances and future opportunities.

Topical route of administration is very important and the most commonly used method of drug delivery for treatment of ocular diseases. However, due to unique anatomical and physiological barriers of eye, it is difficult to achieve the therapeutic concentration in the targeted tissue within the eye. To overcome the effect of these barriers in absorption and to provide targeted and sustained drug delivery, various advances have been made in developing safe and efficient drug delivery systems. Various formulation strategies for ocular drug delivery are used, like basic formulation techniques for improving availability of drugs, viscosity enhancers, and use of mucoadhesives for drug retention and penetration enhancers to promote drug transport to the eye. In this review, we present a summary of the current literature to understand the anatomical and physiological limitations in achieving adequate ocular bioavailability and targeted drug delivery of topically applied drugs and use of new techniques in formulating dosage forms in overcoming these limitations. The recent and future advances in nanocarrier-mediated drug delivery may have the potential to provide patient-friendly and noninvasive techniques for the treatment of diseases related to the anterior and posterior segments of the eye.

Sustained Release of Drug Facilitated Through Chemically Crosslinked Polyvinyl Alcohol-Gelatin (PVA-GE) Hydrogels. A sustainable biomedical approach

Abstract The present study aimed to prepare hydrogel based on polyvinyl alcohol (PVA) and gelatin (Ge) and characterization of PVA/Ge hydrogel for their potential use as a sustained drug delivery system. Polyvinyl Alcohol (PVA) and-Gelatin (Ge) were cross-linked using glutaraldehyde (GA) as a crosslinking agent and hydrochloric acid (HCl) as a catalyst. Different feed polymer ratio and crosslinking agent concentration were used to prepare a series of PVA/Ge hydrogels. The obtained PVA/Ge hydrogels were investigated for dynamic and equilibrium swelling studies. The effect of polymers ratio, degree of crosslinking and pH of the medium on swelling of PVA/Ge hydrogels was investigated. Furthermore, the values of diffusion coefficient (D), volume fraction, polymer-solvent interaction parameter, molecular weight between crosslink and crosslink density were calculated. For swelling studies, 0.05M USP phosphate buffer solutions of different pH (1.2, 5.5, 6.5 and 7.5) were used. For the drug release study, ciprofloxacin HCl was loaded into selected samples as a model drug. The release of drug from these samples was performed for 12 hours in USP phosphate buffers of pH 1.2, 5.5 and 7.5. The release data from these samples were fitted into various kinetic models like zero order, first order, Higuchi and Peppas models to investigate the release mechanism. It was found that by varying the composition of PVA/Ge hydrogel and GA concentration, a significant difference was observed in drug release kinetics. FTIR spectroscopy and X-ray diffraction were used for the characterization of hydrogels. PVA/Ge hydrogel showed sustained release of the model drug at various pH values suggesting its potential use as a sustained drug delivery system.