Sustained Drug Delivery Research Articles

Nanotechnology: Current Developments, Applications and Patents for Non-invasive Topical Cosmetics and Dermatological Therapeutic Delivery

: Nanotechnology exhibits the advancement in the field of invention, by improving the potency of the formulation through the delivery of inventive solutions. To resolve several limita-tions related to conventional formulations, nanotechnology applications are increasing in the cosmetics and dermatological area. Cosmetic and dermatological preparations are considered a thriving branch of the body care arena and their usage has increased dramatically through the past years. Scientists are designing innovative delivery mechanisms and emerging innovations that are presently being utilized in the development of cosmetics. Inventive nanocarriers such as nio-somes, liposomes, microemulsions, nanoemulsions, solid-lipid nanoparticles, nanospheres, and nanostructured (lipid) carriers have substituted the use of traditional drug delivery. These innova-tive nanocarriers have the convenience of better skin permeation, sustained and controlled drug delivery, precise location, higher stability, and greater incorporated capability. Since the usage of cosmetics has increased, the usual delivery system has been substituted by modern delivery ap-proaches. The introduction of newer advancements and novel drug delivery systems make cos-metics and cosmeceuticals more popular with increased market share. This review article on nan-otechnology employed in cosmetics and dermatology emphasizes the numerous innovative nanocarriers designed for cosmetic and dermatologic drug delivery, their negative and positive aspects, and their toxicity.

Silicone-based AC102-loaded cochlear implant coatings protect residual hearing in an animal model of cochlear implantation

Cochlear implant users with residual hearing benefit synergistically from combined electrical stimulation via the cochlear implant and preserved residual hearing after surgery. However, direct mechanical trauma and subsequent inflammation may deteriorate hearing function. AC102, a novel otoprotective pyridoindole with anti-apoptotic and anti-oxidative properties significantly improved hearing recovery following cochlear implantation when administered intratympanically prior to surgery. Additionally, AC102 exerts neurotrophic effects, possibly aiding in the preservation of auditory nerve fibers and spiral ganglion neurons. Rapid clearance of the drug, however, might be a limiting factor to further attenuate the inflammatory response and maintain neuronal health. The aim of the current study was to design an AC102-loaded electrode array for sustained drug delivery and investigate its effects in hearing preservation cochlear implantation.First, the release-kinetics of AC102 were investigated in vitro and modelled by the Higuchi equation of drug release. An electrode array coated with 10% AC102 was manufactured, its release kinetics evaluated, and subsequently tested in vivo. 20 normal hearing Mongolian gerbils were unilaterally implanted with an AC102-loaded or an unloaded control electrode. Compound action potentials were measured prior to cochlear implantation and serially over 28 days. Hair cells, inner hair cell synapses, and auditory nerve fibers were quantified in cochlear whole-mounts by immunofluorescence staining.AC102 release from silicone coating could be predictably modelled by the Higuchi equation of drug release. The electrode array with an AC102-silicone depot enabled non-linear sustained drug release with initially higher release concentrations. In vivo, the AC102-loaded electrode array significantly recovered auditory threshold shifts near the maximum insertion depth over 28 days. In the apical region, a significant recovery was noticed only until day 14, after which threshold shifts aligned between groups. Histologically, AC102-loaded electrodes significantly preserved outer hair cells apical of the maximum insertion depth and inner hair cells and neuronal structures at the tip of the inserted electrode.In conclusion, the drug-loaded electrode arrays could predictably release AC102 over a period of 28 days. AC102 enabled the restoration of auditory thresholds near the area of maximum insertion, which is the desired region to be preserved in cochlear implant recipients with residual hearing.

A wearable osmotic microneedle patch provides high-capacity sustained drug delivery in animal models.

The maintenance of stable plasma drug concentrations within a therapeutic window can be critical for drug efficacy. Here, we developed a wearable osmotic microneedle (OMN) patch to support sustained drug dosing for at least 24 hours without the use of electronic components. The OMN patch uses an osmotic pressure driving force to deliver drug solution into the skin through three hollow microneedles with diameters of less than 200 micrometers. The rate of drug release was related to the composition and concentration of the osmogen and drug and to the physical properties of the semipermeable membrane separating the low- and high-solute compartments. The OMN patch released the peptide drug exenatide in rats and mice for 24 hours, whereas subcutaneous injection resulted in a burst release and rapid decline in the plasma drug concentration. OMN release of exenatide improved glycemic control in a diabetic mouse model consistent with a sustained effective plasma concentration of the drug. Continuous release of the small-molecule chemotherapeutic drug cytarabine reduced the progression of acute myeloid leukemia in mice more effectively than subcutaneous injection. Further evaluation of the OMN patch in canines demonstrated continuous dosing of cytarabine up to 225 milligrams for 24 hours, satisfying clinical requirements (150 to 300 milligrams daily). OMN patches were well tolerated in human participants with minimal pain or irritation of the skin and a stated preference over other administration routes. This wearable drug delivery system could provide a platform for stable high-dose drug release with convenience and safety.

Potential application of matrine microneedles for the treatment of atopic dermatitis in joint skin

Atopic dermatitis (AD) commonly manifests in skin areas subjected to flexion, particularly joints. This underscores the importance of dissolving microneedles (DMNs) used in AD treatment having strong skin adhesion to prevent drug delivery interruption due to patch detachment during patient activity. Moreover, matrine (MAT), a prominent active ingredient derived from the natural plant Sophora flavescens, is known for its significant efficacy in treating skin inflammation, itching, and allergic diseases. Herein, we presented MAT-loaded DMNs (MAT-DMNs) specifically tailored for joint skin application in AD treatment. MAT-DMNs can rapidly dissolve and hydrate after application, demonstrating adhesive properties on ex vivo pig skin, rat abdominal skin, and finger joint skin, thereby ensuring sustained and uninterrupted drug delivery to the skin. In vitro evaluations revealed that MAT-DMNs exhibited 24-hour first-order release profiles with cumulative penetration rates of 78.70 ± 4.24 % and 77.14 ± 6.65 % for the low-dose and high-dose groups, respectively. Furthermore, these DMNs showed excellent skin compatibility and therapeutic efficacy in AD mice models. Specifically, the skin lesion score in MAT-DMNs group was significantly lower (2.67 ± 0.40) compared to the model group (11.60 ± 1.62) and the blank DMNs group (10.80 ± 1.67). MAT-DMNs effectively alleviated AD symptoms such as itching and inflammation by reducing epidermal thickening, decreasing mast cell infiltration, and lowering the expression of Th2 cytokines (IL-4 and IL-10) and pro-inflammatory factors (IL-1β, IL-6, and TNF-α) compared to the blank DMNs group (p < 0.01). These findings suggest that MAT-DMNs hold promise for clinical AD treatment, particularly for skin diseases commonly affecting joint areas.

Self-Exfoliated Guanidinium Covalent Organic Nanosheets as High-Capacity Curcumin Carrier.

Drug administration is commonly used to treat chronic wounds but faces challenges such as poor bioavailability, instability, and uncontrollable release. Existing drug delivery platforms are limited by chemical instability, poor functionality, complex synthesis, and toxic by-products. Presently, research efforts are focused on developing novel drug carriers to enhance drug efficacy. Guanidinium Covalent Organic Nanosheets (gCONs) offer promising alternatives due to their high porosity, surface area, loading capacity, and ability to provide controlled, sustained, and target-specific drug delivery. Herein, we successfully synthesized self-exfoliated gCONs using a Schiff base condensation reaction and embedded curcumin (CUR), a polyphenolic pleiotropic drug with antioxidant and anti-inflammatory properties, via the wet impregnation method. The BET porosimeter exhibited the filling of gCON pores with CUR. Morphological investigations revealed the formation of sheet-like structures in gCON. Culturing human dermal fibroblasts (hDFs) on gCON demonstrated cytocompatibility even at a concentration as high as 1000 µg/mL. Drug release studies demonstrated a controlled and sustained release of CUR over an extended period of 5 days, facilitated by the high loading capacity of gCON. Furthermore, the inherent antioxidant and anti-inflammatory properties of CUR were preserved after loading into the gCON, underscoring the potential of CUR-loaded gCON formulation for effective therapeutic applications. Conclusively, this study provides fundamental information relevant to the performance of gCONs as a drug delivery system and the synergistic effect of CUR and CONs addressing issues like drug bioavailability and instability.

Engineered PVA-tamarind gum-based biocomposite for sustained ophthalmic delivery of moxifloxacin: Effect of nanocellulose on physicochemical, mechanoelectrical and permeation kinetics

Widely used polysaccharide-based films in ophthalmic drug delivery have major limitations of inadequate mechanical strength, poor electrical conductivity, and insufficient ocular drug permeability. Moxifloxacin (MFX) biocomposite film of adequate mechanoelectrical properties was developed for sustained ophthalmic drug delivery. Nanocellulose (NC) incorporated (2.5, 5.0, 7.5, and 10.0 %) PVA-tamarind gum-based moxifloxacin composite was prepared using solvent casting method. The addition of NC improved the mechanical properties of the film, demonstrating its ability to strengthen the structure. Stress relaxation (SR) of the film has been augmented (64.67±7.55 to 73.15±0.34 %) due to increased content of NC (0 to 10 %) respectively. Film containing 5 % NC showed the critical edge of tensile strength (11.9±0.39 MPa), and also the threshold limit of electrical conductivity (4.5*107 Ω). The same film exhibited continued drug release as well as erosion-controlled sustained ocular permeation (pH 7.4) and revealed the highest antibacterial activity (ZOI of disc diffusion, cm) with Pseudomonas aeruginosa (4.63±0.15) and Staphylococcus aureus (4.30±0.26) of MFX (≈224 μg). Notably, incorporating NC produced non-irritating and safe for corneal delivery as confirmed by the Draize model test. Our findings suggested that the NC-containing PVA-tamarind gum-based composite film holds a promising approach for sustained ophthalmic delivery of MFX.

Poly(2-hydroxyethyl methacrylate-co-methacrylated hyaluronan-β-cyclodextrin) hydrogel: A potential contact lens material with high hydrophilicity, good mechanical properties and sustained drug delivery

A novel poly(2-hydroxyethyl methacrylate-co-methacrylated hyaluronan-β-cyclodextrin) [p(HEMA-co-mHA-β-CD)] hydrogel was developed as a potential contact lens for ophthalmic disease. The hydrogel was synthesized from the copolymerization of 2-hydroxyethyl methacrylate (HEMA) monomer and mHA-β-CD as a hydrophilic macromolecular crosslinker. By adjusting the methacrylate substitution degree in hyaluronan (20–29 %) and the mHA-β-CD content (5–11 %), transparent p(HEMA-co-mHA-β-CD) hydrogels were achieved. p(HEMA-co-m20HA-β-CD) hydrogels exhibited an enhanced tensile modulus (from 0.35 to 0.88 MPa) with a decreased elongation at break (from 255 % to 108 %), meanwhile they showed increased hydrophilicity with a decreased water contact angle (from 83.4° to 48.6°) and an increased equilibrium water content (from 38.2 % to 46.4 %). Increasing the mHA-β-CD content resulted in a higher encapsulation and cumulative release of hydrophilic levofloxacin hydrochloride or hydrophobic puerarin, due to the improved hydrophilicity and the formation of β-CD/drug inclusion complexes. Compared with pHEMA hydrogel, p(HEMA-co-m20HA-β-CD) hydrogels better inhibited the deposition of lysozyme and bovine serum albumin, and the bacterial adhesion against S. aureus and E. coli. The hydrogels were stable at physiological conditions and non-toxic to immortalized human keratinocytes. With good mechanical properties, tear protein deposition resistance, antibacterial activity, and sustained drug delivery capabilities, p(HEMA-co-m20HA-β-CD) hydrogels were identified as a promising contact lens material for eye diseases.

Development and characterization of solriamfetol-loaded PVA/PLGA electrospun nanofiber membranes: A promising approach for sustained narcolepsy treatment

Narcolepsy presents challenges in medication adherence and delivery, with traditional oral medications not always suitable for patients experiencing unexpected sleep episodes or difficulty in swallowing pills. This study focused on developing a solriamfetol (SF) loaded nanofiber membrane using a polymer blend of polyvinyl alcohol (PVA) and polylactic-co-glycolic acid (PLGA) for the management of narcoleptic patients with non-oral dosage options. The design required synthesis, optimization, characterization, and evaluation of these nanofibers for transdermal drug delivery. Using a Box-Behnken design, the nanofibers were produced via the electrospinning technique, achieving a high drug content of 96.31 ± 1.21 % and entrapment efficiency of 96.18 ± 1.42 %. The in vitro drug release studies demonstrated a prolonged release profile of SF over 24 h, with 97 % ± 2 % of the drug released. The SEM analysis revealed that the surface morphology of the nanofibers was smooth and homogenous, and the average diameter of the SF/PVA/PLGA nanofibers was found to be 150.23 ± 2.50 nm. X-ray diffraction results confirmed the amorphous structure of the nanofibers. The zebrafish embryonic toxicological study did not reveal any signs of toxicity or morphological abnormalities in the developing embryos, indicating that the nanofibers are safe. The results point to the applicability of SF nanofiber membranes in personalized narcolepsy therapy, which improves patients’ quality of life and the efficacy of their treatment. These nanofibers can be given in the form of a transdermal patch to patients for sustained drug delivery, even when they fall asleep or when they cannot take medicines orally.

An Overview of Film-Forming Emulsions for Dermal and Transdermal Drug Delivery.

Drug delivery through the skin is a widely used therapeutic method for the treatment of local dermatologic conditions. Dermal and transdermal methods of drug delivery offer numerous advantages, but some of the most important aspects of drug absorption through the skin need to be considered. Film-forming systems (FFS) represent a new mode of sustained drug delivery that can be used to replace traditional topical formulations such as creams, ointments, pastes, or patches. They are available in various forms, including solutions, gels, and emulsions, and can be categorised as film-forming gels and film-forming emulsions. Film-forming emulsions (FFE) are designed as oil-in-water (O/W) emulsions that form a film with oil droplets encapsulated in a dry polymer matrix, thus maintaining their dispersed nature. They offer several advantages, including improved solubility, bioavailability and chemical stability of lipophilic drugs. In addition, they could improve the penetration and diffusion of drugs through the skin and enhance their absorption at the target site due to the nature of the components used in the formulation. The aim of this review is to provide an up-to-date compilation of the technologies used in film-forming emulsions to support their development and availability on the market as well as the development of new pharmaceutical forms.

Nanotechnology Based Alternative For The Topical Delivery Of Psoriasis

Psoriasis, a chronic autoimmune disease, is characterized by patches of abnormal skin that are red, pink, or purple, dry, itchy, and scaly. It affects people of all ages, with peak onset between 32 and 52 years old. Psoriasis is classified into three main types: vulgaris, pustular, and inverse. Novel Drug Delivery Systems (NDDS) offer innovative approaches to deliver pharmaceutical substances to the body more effectively and safely. These systems aim to increase bioavailability, maintain therapeutic drug concentrations, and minimize toxicity. Several NDDS are being used for psoriasis treatment, including: • Topical nanoparticles: These offer enhanced skin penetration, controlled release, and reduced side effects. • Liposomes: Spherical vesicles that can encapsulate drugs and deliver them to targeted areas. • Microneedle systems: Create microchannels in the skin for improved drug penetration and localized delivery. • Transdermal patches: Provide non-invasive, sustained drug delivery. • Smart drug delivery systems: Respond to specific stimuli, enabling targeted and controlled drug release

Revolutionizing Eye Care: Exploring the Potential of Microneedle Drug Delivery.

Microneedle technology revolutionizes ocular drug delivery by addressing challenges in treating ocular diseases. This review explores its potential impact, recent advancements, and clinical uses. This minimally invasive technique offers precise control of drug delivery to the eye, with various microneedle types showing the potential to penetrate barriers in the cornea and sclera, ensuring effective drug delivery. Recent advancements have improved safety and efficacy, offering sustained and controlled drug delivery for conditions like age-related macular degeneration and glaucoma. While promising, challenges such as regulatory barriers and long-term biocompatibility persist. Overcoming these through interdisciplinary research is crucial. Ultimately, microneedle drug delivery presents a revolutionary method with the potential to significantly enhance ocular disease treatment, marking a new era in eye care.

Application of high-polarity hydroxyl polyacrylate pressure sensitive adhesive in rizatriptan transdermal drug delivery patch

This study aimed to design a rizatriptan (RIZ) transdermal patch by combining of high-polarity hydroxyl pressure sensitive adhesive (PSA) AAOH-45 with an ion-pair strategy and investigate the molecular mechanism of high content hydroxyl PSA to enhance drug-PSA miscibility. RIZ free base, ion-pair complexes and PSAs containing hydroxyl group were prepared and characterized. Formulation factors including counter-ions, PSAs, drug-loading and others were optimized through single-factor studies and evaluated through pharmacokinetic studies and skin irritation tests. The properties of high polarity PSA and molecular mechanism of drug-PSA miscibility were investigated through molecular simulation, FTIR spectra, 13C NMR spectra, DSC, and rheology study. The optimized formulation contained 20 % (w/w) RIZ-OA (Rizatriptan-Oleic acid), 80 % AAOH-45 (w/w) as the matrix, and had a thickness of 90 μm. Compared with the oral group (MRT0-t = 5.96 ± 0.97 h) and the control patch group (MRT0-t = 11.30 ± 1.78 h), the pharmacokinetic behavior of the optimization group demonstrated sustained drug delivery behavior (MRT0-t = 20.21 ± 0.61 h) with no irritation phenomenon. The miscibility of RIZ with PSAs was positively correlated with the mass percentage of 2-HEA. Higher polar similarity, lower flowability, and stronger intermolecular interaction were responsible for the higher compatibility of high hydroxyl PSA with the drug. This study provided a reference for increasing the drug-loading in PSA and developing RIZ patch.

Nanomaterial-Enhanced Microneedles: Emerging Therapies for Diabetes and Obesity.

Drug delivery systems (DDS) have improved therapeutic agent administration by enhancing efficacy and patient compliance while minimizing side effects. They enable targeted delivery, controlled release, and improved bioavailability. Transdermal drug delivery systems (TDDS) offer non-invasive medication administration and have evolved to include methods such as chemical enhancers, iontophoresis, microneedles (MN), and nanocarriers. MN technology provides innovative solutions for chronic metabolic diseases like diabetes and obesity using various MN types. For diabetes management, MNs enable continuous glucose monitoring, diabetic wound healing, and painless insulin delivery. For obesity treatment, MNs provide sustained transdermal delivery of anti-obesity drugs or nanoparticles (NPs). Hybrid systems integrating wearable sensors and smart materials enhance treatment effectiveness and patient management. Nanotechnology has advanced drug delivery by integrating nano-scaled materials like liposomes and polymeric NPs with MNs. In diabetes management, glucose-responsive NPs facilitate smart insulin delivery. At the same time, lipid nanocarriers in dissolving MNs enable extended release for obesity treatment, enhancing drug stability and absorption for improved metabolic disorder therapies. DDS for obesity and diabetes are advancing toward personalized treatments using smart MN enhanced with nanomaterials. These innovative approaches can enhance patient outcomes through precise drug administration and real-time monitoring. However, widespread implementation faces challenges in ensuring biocompatibility, improving technologies, scaling production, and obtaining regulatory approval. This review will present recent advances in developing and applying nanomaterial-enhanced MNs for diabetes and obesity management while also discussing the challenges, limitations, and future perspectives of these innovative DDS.

Acid-triggered rattan ball-like β-glucan carrier embedding doxorubicin to synergistically alleviate precancerous lesions of gastric cancer via p53 and PI3K pathways

The early intervention of precancerous lesions of gastric cancer (PLGC) is crucial for improving the survival of patients with gastric cancer. Traditional pharmaceuticals for the treatment of PLGC are limited by side effects, thus developing innovative drug carrier that are more efficient but without the undesirable side effects is required. Here, we proposed an acid-triggered mushroom-derived β-glucan carrier embedding doxorubicin (DOX) to circumvent drug cytotoxicity and synergistically alleviate PLGC based on the controlled conformational transformation. The triple helix β-glucan extracted from Dictyophora rubrovolvata (DRP) loaded doxorubicin driven by pH and DMSO regulation, forming two rattan ball-like nanoparticles (DRP-DOX(pH) and DRP-DOX(DMSO)) via its collapse and recombination of triple-helix conformation. The findings revealed that DRP-DOXs achieved acid-triggerable and sustained drug delivery with an average particle size of 500 nm and 550 nm. In vitro evaluation of GES-1 cells showed DRP-DOXs reduced reactive oxygen species (ROS) production and altered mitochondrial membrane potential. Compared to DRP-DOX(DMSO) and DRP, DRP-DOX(pH) could more effectively downregulate cellular oxidative stress and inflammation to eventually alleviate PLGC, by regulating the p53 and PI3K pathways to mitigate gastric mucosa damage. Consequently, the nature-derived β-glucan delivery nanovesicle holds great promising applications in reducing drug toxicity and suppressing the development of PLGC.

One-pot biocatalysis of potato rhamnogalacturonan and the role of its deacetylation in efficient inhibition of colon cancer cells and hydrogel mediated colon-targeted drug delivery

Deacetylation of potato rhamnogalacturonan (PRG) by rhamnogalacturonan acetyl esterase (CtPae12B) was explored for enhanced hydrolysis of PRG by rhamnogalacturonan lyase (CtRGLf) and the effects of deacetylated PRG were studied in enhancing inhibition of colon-cancer cells and formation of colon-targeting drug delivery material. Pre-treatment of PRG with CtPae12B resulted in increased relative activity of CtRGLf. CtPae12B removed acetyl groups from both O-2 and O-3 positions of D-galactopyranosyluronic acid residues of PRG, resulting in 98 % deacetylation. PRG displayed 21.9 % degree of acetylation and 7.7 % degree of methylation. TLC and ESI-MS analysis of CtRGLf hydrolysed PRG showed unsaturated RG di-saccharide as the smallest product, with m/z 322. Deacetylated PRG-oligosaccharides displayed higher, 50 % inhibition of colon-cancer HCT-116 cells (with shrunken and globular morphology) than 35 % inhibition by acetylated PRG-oligosaccharides. FESEM and BET analysis of CtPae12B-treated PRG showed porous structure and significantly higher total surface area and pore volume than non-enzyme treated PRG. Higher drug entrapment efficiency and lower drug release rate of CtPae12B-treated PRG hydrogel (0.0033 min−1 at pH 1.2 and 0.009 min−1 at pH 7.4), than non-enzyme treated PRG hydrogel, (0.0057 min−1 at pH 1.2 and 0.02 min−1 at pH 7.4), showed it to be a potential biomaterial for sustainable colon-targeted drug delivery.

Eco-Friendly Microwave Synthesis of Sodium Alginate-Chitosan Hydrogels for Effective Curcumin Delivery and Controlled Release.

In this study, we developed sodium alginate-chitosan hydrogels using a microwave-assisted synthesis method, aligning with green chemistry principles for enhanced sustainability. This eco-friendly approach minimizes chemical use and waste while boosting efficiency. A curcumin:2-hydroxypropyl-β-cyclodextrin complex was incorporated into the hydrogels, significantly increasing the solubility and bioavailability of curcumin. Fourier Transform Infrared Spectroscopy (FTIR) analysis confirmed the structure and successful incorporation of curcumin, in both its pure and complexed forms, into the polymer matrix. Differential scanning calorimetry revealed distinct thermal transitions influenced by the hydrogel composition and physical cross-linking. Hydrogels with higher alginate content had higher swelling ratios (338%), while those with more chitosan showed the lowest swelling ratios (254%). Scanning Electron Microscopy (SEM) micrographs showed a porous structure as well as successful incorporation of curcumin or its complex. Curcumin release studies indicated varying releasing rates between its pure and complexed forms. The chitosan-dominant hydrogel exhibited the slowest release rate of pure curcumin, while the alginate-dominant hydrogel exhibited the fastest. Conversely, for curcumin from the inclusion complex, a higher chitosan proportion led to the fastest release rate, while a higher alginate proportion resulted in the slowest. This study demonstrates that the form of curcumin incorporation and gel matrix composition critically influence the release profile. Our findings offer valuable insights for designing effective curcumin delivery systems, representing a significant advancement in biodegradable and sustainable drug delivery technologies.

Enzyme-responsive microgel with controlled drug release, lubrication and adhesion capability for osteoarthritis attenuation

The treatment of osteoarthritis (OA) remains challenging due to the narrow therapeutic window and rapid clearance of therapeutic agents, even with intra-articular administration, resulting in a low treatment index. Recent advancements in local drug delivery systems have yet to overcome the issues of uncontrolled burst release and short retention time, leading to suboptimal OA treatment outcome. Herein, we developed a methacrylate-crosslinking hyaluronic acid (HA) microgel (abbreviated as CXB-HA-CBP) that covalently conjugates the anti-inflammatory drug celecoxib (CXB) via a metalloproteinase-2 (MMP-2)-responsive peptide linker (GGPLGLAGGC) and a collagen II binding peptide (WYRGRLC). The GGPLGLAGGC linker is specifically cleaved by the overexpressed MMP-2 enzyme within the OA joint, enabling the sustained and on-demand release of CXB entity. The synergistic action of CXB and HA effectively inhibited macrophage activation and reduced the production of pro-inflammatory cytokines, protecting chondrocytes from damage. Furthermore, the collagen II peptide introduced on the microgel surface enabled a cartilage-binding function to form an artificial lubrication microgel layer on the cartilage surface to reduce cartilage wear. The CXB-HA-CBP microgel showed an extended retention time of up to 18 days in the affected joint, leading to an effective OA treatment in rats. This sophistically designed microgel, characterized by the prolonged retention time, sustained drug delivery, and enhanced lubrication, presents a promising biomedicine for OA treatment. Statement of significanceA new methacrylate-crosslinking hyaluronic acid (HA) microgel, covalently conjugated with the celecoxib (CXB)-GGPLGLAGGC and the collagen II binding peptide (CBP, peptide sequence: WYRGRLC), was developed. The overexpressed MMP-2 in OA joint cleaved the GGPLGLAGGC linker to trigger the CXB moiety release. Besides, the CBP on the surface of microgels enabled a cartilage-attaching ability, resulting in a prolonged retention time and an improved lubrication property in joint. This advanced drug-loading microgel remarkably reduced macrophage activation and pro-inflammation cytokine production, while protecting the chondrocytes via a dual action of CXB and HA. This study demonstrated that the enzyme-responsive drug-loading microgel could serve as an platform to efficiently attenuate osteoarthritis.

Unlocking The Potential Of Natural Polymers: A Comparative Study For Innovative Drug Delivery Systems

This study aims to characterize and compare four biopolymers - pectin, guar gum, xanthan gum, and sodium alginate - for their potential use in drug delivery systems by evaluating their hydrophilicity, pH sensitivity, and thermosensitivity. Biopolymer films were prepared and subjected to water absorption tests for hydrophilicity, gravimetric analysis in varying pH conditions for pH sensitivity, and weight change measurements after heat exposure for thermosensitivity. Each test was conducted in five trials to ensure reliability. Pectin demonstrated the highest responsiveness across all tests, showing rapid water absorption (6.46 seconds), significant pH sensitivity (0.53g weight change in acidic conditions), and high thermosensitivity (0.378g weight change). Guar gum showed moderate responsiveness, while xanthan gum and sodium alginate exhibited the most stability across varying conditions. Pectin's high responsiveness suggests suitability for smart, multi-stimuli-responsive systems. Guar gum's moderate responsiveness indicates potential for controlled release formulations. The stability of xanthan gum and sodium alginate makes them ideal for applications requiring consistent drug release in diverse physiological environments. This study offers a comprehensive, comparative analysis of four widely used biopolymers, filling a gap in the existing literature. The results provide a foundation for developing tailored, sustainable drug delivery systems, contributing to the advancement of personalized medicine and environmentally friendly pharmaceutical practices

Investigating a novel therapeutic composition for dry eye syndrome management: In vitro and in vivo studies

Dry eye syndrome (DES) presents a significant challenge in ophthalmic care, necessitating innovative approaches for effective management. This research article introduces a multifaceted strategy to address DES through the development of ocular inserts utilizing advanced technologies such as hot-melt extrusion (HME) and the CaliCut post-extrusion system. The formulation includes key ingredients targeting different layers of the tear film and associated inflammation, including hydroxypropyl cellulose (HPC), polyethylene glycol (PEG), castor oil, and dexamethasone. The study incorporates a Design of Experiments (DoE) approach, integrating HME and the precise stretching and cutting technique of CaliCut for manufacturing consistency and dimensional control of the inserts. The developed insert(s) have been systematically characterized for their physicochemical properties, release profile, and in vivo efficacy. In silico molecular docking studies have also been conducted to assess the binding affinities of formulation components with ocular mucin, elucidating their binding affinities. Preliminary results demonstrate promising potential for the developed insert in managing DES, offering preservative-free treatment, sustained drug delivery, and improved patient compliance. This study highlights the integration of advanced technologies and formulation strategies in ocular drug delivery for effective DES management.

Nanoemulgels: A new approach for the treatment of skin-related disorders

Skin-related disorders like psoriasis, dermatitis, acne, and wounds affect a major sector of the global population. Conventional treatment modalities exhibit limitations encompassing systemic adverse effects, suboptimal skin permeability, and variable drug release kinetics. Nanoemulsion-based hydrogels, also known as nanoemulgels, have emerged as a promising approach for topical and transdermal drug delivery, particularly in treating skin disorders. These have the advantages of nanoemulsions and hydrogels, offering enhanced therapeutic efficacy. Further, nanoemulgels can facilitate controlled and sustained drug delivery, reducing the frequency of application and improving patient compliance. These nanoemulgels hold significant prospects in topical and transdermal applications, particularly in delivering therapeutic cargo in diseases such as mycoses, atopic dermatitis, and psoriasis. This review will outline the functions of nanoemulgels, the building blocks of nanoemulgels, their formulation techniques, evaluation parameters, and their pharmacological applications. Further, an overview of the current state of research in the field of nanoemulgels, future directions, and challenges associated with nanoemulgels was also provided.