Chitosan conjugates in precision medicine: from synthesis to their role in advanced drug delivery.

Objective: The current study aimed to develop and optimize a liposomal gel for topical baclofen delivery to enhance skin permeation and therapeutic efficacy in muscle spasticity. Methods: A thin film hydration approach was used to create liposomes loaded with Baclofen. To optimize the baclofen liposomes, the effects of lipid concentration and hydration volume on vesicle size and entrapment efficiency were examined using a 32 full factorial design. A topical liposomal gel was created by incorporating an optimized baclofen liposome batch into a 1% Carbopol gel, and it was assessed for many parameters. Results: The optimized formulation demonstrated a mean vesicle size of 244.6 ± 3.34 with a PDI of 0.145 and an entrapment efficiency of 63.78 ± 2.66. The values from the experiments were very close to the predicted values given by the software, with a result error of ±5%, confirming the reliability of the statistical model at 95% confidence interval. A zeta potential of -28.8 mV for optimized formulation reflected good physical stability. The formulated liposomes were found to have a smooth surface texture with discrete particles in spherical shape as demonstrated in TEM analysis. The release profile of the drug from the liposomal gel formulation has shown a sustained release pattern up to 8 hrs with maximum release of 96.95%, following the Higuchi drug release kinetics model with non-Fickian diffusion as predicted by Kores-Peppas model. The in vivo skin irritation test conducted on Wistar rats revealed no signs of irritation. Furthermore, the histopathological evaluation established the safety of the formulation for topical application. Conclusion: It was concluded that the Baclofen-loaded topical liposomal gel represents a promising drug delivery approach for the treatment of muscle spasticity.

Background: Chronic and acute wounds remain a significant clinical challenge due to delayed healing, infection risk, and limitations of conventional topical therapies. The integration of medicinal plant-derived bioactives with nanotechnology offers a promising strategy to enhance wound repair and therapeutic outcomes. Aim: This study aimed to develop and evaluate a novel topical nano-hydrogel formulation containing Adina cordifolia leaf extract-mediated Copper Oxide (CuO) nanoparticles for enhanced wound healing activity. Methods: CuO nanoparticles were synthesised using a green synthesis approach employing A. cordifolia leaf extract and characterised by UV-visible spectroscopy, X-ray Diffraction (XRD), particle size analysis, and zeta potential measurement. The nanoparticles were incorporated into a Carbopol 934-based hydrogel. Formulation optimisation was performed using a central composite design, generating thirteen formulations (HGL1-HGL13). The optimised formulation was evaluated for in vitro drug release kinetics, drug-excipient compatibility, stability, and model validation. In vivo wound healing efficacy was assessed in Wistar rats by monitoring wound contraction and epithelialisation over 15 days. Results: The synthesised CuO nanoparticles showed a mean particle size of 365.3 ± 118.2 nm and a zeta potential of −26.6 mV, indicating good stability. UV-visible spectroscopy (λmax 264 nm) and XRD peaks at 35° and 38° confirmed nanoparticle formation and crystalline nature. Among all formulations, HGL7 exhibited optimal performance with 81% cumulative drug release over 12 h following zero-order kinetics (R2 = 1). Compatibility and validation studies confirmed formulation stability and high predictability (bias < ±1%). In vivo studies demonstrated significantly enhanced wound contraction and epithelialisation in nano-hydrogel-treated animals compared to conventional treatment. Conclusion: The developed A. cordifolia-based CuO nano-hydrogel represents a stable, reproducible, and effective topical formulation that significantly enhances wound healing. This study highlights the potential of combining traditional herbal medicine with nanotechnology for advanced wound care and future clinical and commercial applications. Major Findings: The study developed a stable nano-hydrogel using green-synthesised CuO nanoparticles from A. cordifolia, showing optimal properties and controlled drug release. The optimised formulation (HGL7) significantly accelerated wound contraction and epithelialisation in vivo. These findings demonstrate its strong potential as an effective advanced wound care treatment.

pH-sensitive liposomes represent a promising platform for targeted drug delivery, with imidazole-based lipids offering unique advantages for tumor-specific release and enhanced endosomal escape. This pH-responsiveness facilitates cellular uptake through electrostatic interactions and improves intracellular delivery, primarily via the proton sponge effect and membrane fusion mechanisms. This article provides a comprehensive overview of imidazole-modified liposomes, detailing their pH-responsiveness mechanisms, diverse formulations, and highlighting current gaps and future research directions within the field. Special attention is given to the characteristics, advantages, and applications of key structures, including imidazole-lipid compounds, imidazole-cholesterol conjugates, and histidine-bearing polymers. The incorporation of imidazole has been shown to optimize drug release profiles, enhance intracellular delivery, and improve cytotoxicity toward cancer cells, while maintaining a favorable safety profile under physiological conditions comparable to conventional liposomes. Recent advancements highlight the impact of structural modifications, such as carbon chain length optimization, conjugated moieties, and polymer architecture, on modulating liposome stability, drug release kinetics, and targeting efficiency. Despite these notable advancements, significant challenges persist, including the critical balance between carrier stability and pH sensitivity, immune clearance, endosomal entrapment, and the complexities associated with large-scale synthesis.

Biodegradable polymers have emerged as essential components in advanced drug delivery systems, enabling controlled, sustained, and site-specific therapeutic release while minimizing systemic toxicity. This comprehensive review covers the design principles, degradation mechanisms, and drug release dynamics of natural and synthetic biodegradable polymers such as PLGA, PCL, chitosan, and alginate. Their adaptability allows fabrication into nanoparticles, microspheres, hydrogels, and scaffolds tailored to various clinical needs, including cancer therapy, vaccine delivery, gene therapy, and tissue engineering. The review discusses hydrolytic and enzymatic degradation processes, surface versus bulk erosion behaviors, and factors influencing polymer degradation and drug release kinetics. Case studies highlight FDA-approved formulations leveraging these polymers for enhanced therapeutic efficacy and patient compliance. Challenges such as variability in degradation rates, formulation stability, manufacturing scale-up, and regulatory hurdles are addressed. Emerging frontiers in smart stimuli-responsive systems, hybrid polymers, AI-driven design, and personalized medicine underscore the future potential of biodegradable polymers as cornerstones of precision and sustainable therapeutics.

The limited penetration of nanomedicines into tumor tissues remains a major obstacle to their therapeutic efficacy. To overcome this barrier, we designed a novel nanodrug that leverages receptor/cation dual pathway-mediated transcytosis to achieve deep tumor penetration and targeted disruption of mitochondria, resulting in significantly enhanced antitumor outcomes. The multifunctional carrier, P1, was constructed through the synthesis of an amphiphilic block copolymer, terminal conjugation of the CRGDK peptide, and side-chain modification with 7-diethylaminocoumarin (DEAC) for mitochondrial targeting. Dynamic light scattering analyses confirmed the pH/ROS-responsive behavior of P1 micelles, including acid-triggered charge reversal. Drug release kinetics, cellular uptake and endocytic mechanisms, lysosomal escape efficiency, mitochondrial colocalization, induction of ROS generation, mitochondrial membrane potential (ΔΨm) depolarization, apoptosis induction, penetration in multicellular tumor spheroids (MTSs) and in vivo tumors, and antitumor efficacy (in vitro and in vivo) were systematically evaluated. Results indicated that DOX/P1 micelles initially target tumor tissue via CRGDK binding, followed by NRP-1-mediated transcytosis. Subsequent acidity-induced charge reversal activates a secondary cation-mediated transcytosis pathway, synergistically promoting deep tumor infiltration. Upon mitochondrial localization, the carrier undergoes ROS-triggered degradation, leading to concurrent release of doxorubicin (DOX) and cinnamaldehyde (CA) within mitochondria. This dual release acts synergistically to amplify oxidative stress, collapse ΔΨm, and induce mitochondrial DNA damage, collectively precipitating irreversible apoptosis. This study establishes a programmable platform for developing tumor-penetrating nanotherapeutics with precise subcellular organelle-targeting capabilities.

Bone tissue engineering requires scaffolds that mimic the native extracellular matrix and provide sustained delivery of osteoinductive factors. This study focuses on developing a multifunctional scaffold using a green electrospinning process to combine the biocompatibility of silk fibroin (SF) with a non-viral gene delivery system for sustained expression of Bone Morphogenetic Protein 2 (BMP2). A green electrospinning technique, using an aqueous SF and polyethylene oxide (PEO) solution, was employed to fabricate nanofibrous scaffolds, eliminating the use of harsh organic solvents. Polyethylenimine (PEI) modified liposomes (LipoPEI) were used to encapsulate a BMP2-encoding plasmid (pDNA Bmp2 ). These gene-loaded nanoparticles were incorporated into the SF-PEO nanofibers. The resulting scaffolds were characterized for morphology (SEM), structure (FTIR, XRD), and drug release kinetics. Biological performance was evaluated by assessing cell viability (MTT assay), cell attachment (SEM), gene transfection efficiency (confocal microscopy), and osteogenic differentiation (alkaline phosphatase (ALP) activity, Alizarin Red S staining) using bone marrow mesenchymal stem cells (BMSCs). Physicochemical characterization confirmed the successful formation of uniform pDNABmp2@LipoPEI nanocomplexes with a particle size of approximately 266 nm and a positive surface charge of +16.9 mV. These nanocomplexes were homogeneously incorporated into smooth, bead-free SF-PEO nanofibers with average diameters ranging from 460 to 541 nm. The composite scaffold demonstrated a highly sustained release of pDNABmp2 over 14 days. In vitro studies using rat bone marrow-derived mesenchymal stem cells (BMSCs) revealed that the scaffold possesses excellent biocompatibility, promoting robust cell adhesion, spreading, and proliferation. Furthermore, the gene-loaded scaffold successfully mediated the transfection of BMSCs, leading to significant upregulation of osteogenic markers, including alkaline phosphatase (ALP) activity and extensive calcium mineral deposition over 21 days. The novel composite scaffold combines the structural advantages of SF with a sustained BMP2 gene delivery system, showing remarkable potential to promote osteogenic differentiation. This work presents a promising, environmentally friendly, and effective platform for bone tissue engineering and regenerative medicine.

Development of 3D-printed chitosan/p-coumaric acid scaffolds for wound healing: antibacterial properties and drug release kinetics.

Effects of hydrophobic chain lengths on the structure and properties of polymeric micelles: experimental and simulation studies.

Bioengineered chitosan/silk scaffold encapsulated with quercetin nanoparticles accelerates wound healing in a diabetic rat skin defect model.

Advanced gentamicin-loaded chitosan/hydroxyapatite/mesoporous SiO2 scaffold: A comprehensive investigation of drug delivery and cellular interactions.

Engineering chitosan-functionalized liposomes for targeted drug delivery and biomedical applications.

Fabrication and characterization of taste-masked core-shell nanofibre mats for dual drug delivery of antihypertensives in pediatrics.

Recent updates in alginate as a promising biopolymer in cancer therapy: A review.

ABSTRACT Polymer–drug conjugates have seen limited exploration in antimalarial therapy, despite their successful development for cancer and other diseases. With rising resistance and a critical shortage of first‐line treatments for severe malaria, innovative drug delivery strategies are urgently needed to maximize the currently available drugs. Building on our previous work that demonstrated a water‐soluble polymer–lumefantrine conjugate for the intravenous treatment of severe malaria, we investigated the influence of linker chemistry on drug release rate and kinetics of a new polyethylene glycol‐lumefantrine conjugate under conditions relevant to malaria pathophysiology. Four homologous aliphatic diacid linkers (succinic, glutaric, adipic, and dodecanedioic acids) containing 4, 5, 6, and 12 carbon atoms, respectively, were introduced between the polymer and the drug. The conjugates were structurally well‐defined and selectively cleaved at the ester bond under acidic conditions (pH 5.5), releasing only free lumefantrine, while remaining stable in human plasma (pH 7.4). Drug release rates were inversely proportional to linker length, with only the succinic acid‐linked conjugate, which exhibited an initial burst release, deviating from first‐order kinetic models. Complete inhibition of the Plasmodium falciparum NF54 strain was observed in vitro with a divalent variant of the succinic acid‐linked conjugate, underscoring its potential for effective therapeutic action.

Development of a controlled-release tofacitinib formulation using acid-sensitive pore-forming components for an osmotic drug delivery system.

Electrospinning is an innovative process that produces polymeric fibres for a variety of purposes, including controlled hormone administration. These fibres are made from biopolymers like chitosan, cellulose, alginate, and starch, and have attracted interest for their capacity to encapsulate hormones and release them in a regulated way, therefore Increasing bioavailability and stability. The article investigates the utilization of smart electrospun fibers for hormone delivery, alongside a focus on their potential to improve therapeutic results. Electrospun fibres can encapsulate hormones such as insulin, melatonin, and contraceptives for regulated and prolonged release. This method addresses difficulties in traditional hormone delivery, like frequent insulin injections or hormone instability in biological circumstances. Techniques like coaxial electrospinning enable the development of core-shell structures, which further optimize release profiles. The use of these fibres for diabetic management, wound healing, and long-term contraception represents substantial advances in patient care. The flexibility of fibres also allows for precise regulation of drug release kinetics, which improves the efficacy of hormone therapy while reducing adverse effects. Smart electrospun food fibres have enormous promise for the future of hormone administration, providing longer-lasting, more focused, and effective therapies. Their flexibility, along with ongoing advances in electrospinning processes, positions them as a viable tool in contemporary medicine.

Correlation between permeability of pectin-ethylcellulose films and drug release from coatings under variable processing conditions.

Injectable Schiff base-engineered hydrogel for spatiotemporal liraglutide delivery orchestrates diabetic periodontitis regression via multimodal microenvironment reprogramming.

Research progress and prospect of preparation and long-acting drug release of polyester drug-loaded microspheres.