Sustained Release Research Articles

Sustained intra-cellular siRNA release from poly(L-arginine) multilayered nanoparticles for prolonged gene silencing

ABSTRACT Background Sustained siRNA release from nanocarriers is difficult to achieve inside the cell after entry: typically, all nanocarriers exhibit burst release of the cargo into the cytoplasm. Research design and methods Layer-by-layer (LbL) nanoparticles (NPs) can be constructed so that they escape endosomes intact, and subsequently exhibit sustained release of the cargo. Our work quantifies intra-cellular siRNA release from multilayered NPs, evaluates mechanism behind the sustained release, and optimizes the duration of release. Results Intra-cellular studies showed that NPs developed with four layers of poly-L-arginine, alternated with three layers of siRNA layers, were able to elicit effective and prolonged SPARC knockdown activity over 21 days with a single-dose treatment. For the first time, we have quantified the amounts of released siRNA in the cytoplasm and the amount of siRNA remaining inside the NPs at each timepoint. Furthermore, we have correlated the amount of released siRNA within cells by LbL NPs to the cellular knockdown efficiency of multilayered delivery system. Conclusions This methodology may provide an excellent screening tool for assessing the duration of gene silencing by various nanocarrier formulations.

Evaluating the efficacy of Rose Bengal-PVA combinations within PCL/PLA implants for sustained cancer treatment.

The current investigation aims to address the limitations of conventional cancer therapy by developing an advanced, long-term drug delivery system using biocompatible Rose Bengal (RB)-loaded polyvinyl alcohol (PVA) matrices incorporated into 3D printed polycaprolactone (PCL) and polylactic acid (PLA) implants. The anticancer drug RB's high solubility and low lipophilicity require frequent and painful administration to the tumour site, limiting its clinical application. In this study, RB was encapsulated in a PVA (RB@PVA) matrix to overcome these challenges and achieve a localised and sustained drug release system within a biodegradable implant designed to be implanted near the tumour site. The RB@PVA matrix demonstrated an RB loading efficiency of 77.34 ± 1.53%, with complete RB release within 30min. However, when integrated into implants, the system provided a sustained RB release of 75.84 ± 8.75% over 90 days. Cytotoxicity assays on PC-3 prostate cancer cells indicated an IC50 value of 1.19 µM for RB@PVA compared to 2.49 µM for free RB, effectively inhibiting cancer cell proliferation. This innovative drug delivery system, which incorporates a polymer matrix within an implantable device, represents a significant advancement in the sustained release of hydrosoluble drugs. It holds promise for reducing the frequency of drug administration, thereby improving patient compliance and translating experimental research into practical therapeutic applications.

Dipyridamole-grafted copolymer electrospun nanofiber membranes for suppression of peritendinous adhesions

Post-traumatic tendon adhesions significantly affect patient prognosis and quality of life, primarily stemming from the absence of effective preventive and curative measures in clinical practice. Current treatment modalities, including surgical excision and non-steroidal anti-inflammatory drugs, frequently exhibit limited efficacy or result in severe side effects. Consequently, the use of anti-adhesive barriers for drug delivery and implantation at the injury site to address peritendinous adhesion (PA) has attracted considerable attention. Electrospun nanofiber membranes (ENMs) have been extensively employed as drug-delivery platforms. In this study, we fabricated a polylactic acid (PLA)–dipyridamole (DP)-graft copolymer ENM called PLC-DP. This membrane exhibits enzyme-sensitive features, allowing more controlled and sustained drug release compared with conventional drug-loaded ENMs. In experiments, PLC-DP implantation reduced tissue adhesion by 47 % relative to the control group while not adversely affecting tendon healing. Mechanistically, PLC-DP effectively activates the FXYD domain containing ion-transport regulator 2 (FXYD2) protein, thereby downregulating the fibroblast-transforming growth factor beta (TGF-β)/Smad3 signaling pathway. PLC-DP leverages the anti-adhesive properties of DP and the enzyme-sensitive characteristics of graft copolymers, providing a promising approach for the future clinical treatment and prevention of PA. Statement of significancePeritendinous adhesions (PA) are a common and disabling condition that seriously affects the prognosis and quality of life of post-trauma patients. Current treatments often have limited efficacy or severe side effects, leaving a serious gap in clinical practice. We developed a significant biomaterial, poly(lactic acid)-dipyridamole graft copolymer electrospun nanofibrous membrane (PLC-DP), specifically for PA inhibition. In addition, this study uniquely combines dipyridamole, an anti-adhesive agent, and enzyme-sensitive copolymers in electrospun nanofibrous membrane. Unlike conventional drug-loaded electrospun nanofibrous membranes, PLC-DPs have enzyme-sensitive drug properties that allow for sustained drug release on demand. Our experiments showed that implantation of PLC-DP was effective in reducing tissue adhesions by 47 % without affecting tendon healing. We elucidated the mechanism behind this phenomenon, suggesting that PCD activates FXYD2 to inhibit TGF-β-induced expression of Col III, which is a key factor in PA development.

Nanocarrier-Based Delivery Approaches of Mangiferin: An Updated Review on Leveraging Biopharmaceutical Characteristics of the Bioactive.

In recent years, bioactive constituents from plants have been investigated as an alternative to synthetic approaches of therapeutics. Mangiferin (MGF) is a xanthone glycoside extracted from Mangifera indica and has shown numerous medicinal properties, such as antimicrobial, anti-diarrhoeal, antiviral, anti-inflammatory, antihypertensive, anti-tumours, and anti-diabetic effects. However, there are numerous challenges to its effective therapeutic usage, including its low water solubility, limited absorption, and poor bioavailability. Nano formulation approaches in recent years exhibited potential for the delivery of phytoconstituents with key benefits of high entrapment, sustained release, enhanced solubility, stability, improved pharmacokinetics, and site-specific drug delivery. Numerous techniques have been employed for the fabrication of MGF-loaded Nano formulations, and each technique has its advantages and limitations. The nanocarriers that have been employed to fabricate MGF nanoformulations for various therapeutic purposes include; polymeric nanoparticles, nanostructure, lipid carriers, polymeric micelles, Nano emulsions, microemulsion & self-microemulsifying drug delivery system, solid lipid nanoparticles, gold nanoparticles, carbon nanotubes, transfersomes, nanoliposomes, ethosomes & transethosomes, and glycethosomes. Different biopharmaceutical characteristics (size, shape, entrapment efficiency, zeta potential, in vitro drug release, ex vivo drug permeation,, and in vivo studies) of the mentioned MGF-loaded nanocarriers have been methodically discussed. Patent reports are also included to further strengthen the potential of MGF in the management of diseases.

Roflumilast-loaded nanostructured lipid carriers attenuate oxidative stress and neuroinflammation in Parkinson’s disease model

Parkinson’s disease (PD) is a progressive neurodegenerative disorder with limited symptomatic treatment options. Targeting phosphodiesterase 4 (PDE4) has shown a promising result in several preclinical studies. In our study, we aim to repurpose US FDA-approved PDE4 inhibitor for PD. Through in-silico study, we identified roflumilast (ROF) as the potential candidate targeting PDE4B2. In Drosophila PD expressing the A30P mutant α-synuclein model, ROF exhibited anti-PD effects as indicated by negative geotaxis and antioxidant activities. Given the low brain distribution of ROF (<50%) at clinical doses, incorporation into nanostructured lipid carriers (NLCs) was carried out to enhanced blood-brain barrier permeability. In vitro release studies indicated sustained ROF release from NLCs (≈75%) over 24 h. Single-dose oral toxicity studies reported no mortality or toxicity signs. ROF-loaded NLCs significantly alleviated behavioural deficits, increased antioxidant parameters (p < 0.05), and reduced TNF-α and IL-6 levels (p < 0.5) in the striatum compared to pure ROF. ROF-loaded NLCs demonstrated potential anti-PD effects with high efficacy than pure ROF. Our study suggests that nanostructured lipid carriers (NLCs) can be a promising drug delivery system to overcome limitations associated with poor brain bioavailability of lipophilic drugs like ROF for PD treatment. Further investigation related to brain occupancy and underlying mechanisms of our formulation is warranted to confirm and strengthen our current findings.

Negatively Charged Thermosensitive Hydrogel Loaded with Pectin Microspheres to Recover the Mucosal Barrier for Ulcerative Colitis Therapy.

Ulcerative colitis (UC), a chronic inflammatory bowel disease, poses a heightened colorectal cancer risk due to persistent mucosal inflammation and barrier dysfunction. In this article, a negatively charged thermosensitive hydrogel loaded with pectin microspheres was used as the enema for UC treatment. Succinic acid was immobilized on poly(ε-caprolactone-co-glycolide)-poly(ethylene glycol)-poly(ε-caprolactone-co-glycolide) (PCLGA-PEG-PCLGA) triblock copolymers to preferentially coat on cationic-inflamed sites via electrostatic interaction for reconstructing the mucosal barrier. Anti-inflammation drug 5-aminosalicylic acid (5-ASA) and curcumin-loaded pectin microspheres (Pec@Cur) were dispersed in the hydrogel for the inflammatory treatment of UC. The thermally sensitive hydrogels were rectally injected into UC model mice. The hydrogel effectively adhered to ulcers and prolonged colon retention, enabling sustained drug release and remarkably relieving the symptoms of colitis. The negatively charged hydrogel exhibited excellent significance in the UC treatment.

Optimizing locally delivered periodontitis therapy: Development of chitosan‐hydroxyapatite‐encapsulated drug via electrospraying

AbstractThis study presents the development of an optimized drug delivery system for periodontitis treatment utilizing chitosan‐hydroxyapatite nanoparticles. Employing the electrospraying technique, researchers encapsulated the antibiotic amoxicillin within chitosan‐hydroxyapatite composite matrices while varying the concentrations of chitosan and hydroxyapatite nanoparticles. The resulting microparticles displayed sizes ranging from 276 to 386 μm. Characterization of the produced drug encapsulations indicated that higher concentrations of chitosan and hydroxyapatite resulted in the formation of larger particles with rougher surfaces, increased mechanical strength, and enhanced thermal stability. Notably, nanoindentation analysis revealed an increase in hardness from 0.21 to 0.35 GPa, and in elastic modulus from 5.32 to 8.72 GPa with escalating chitosan and hydroxyapatite content, meeting or surpassing requirements for load‐bearing regenerative biomaterials. In vitro drug release assessments exhibited sustained amoxicillin release over 24 h, predominantly through diffusion and dissolution mechanisms. Formulations with lower polymer and mineral content showcased elevated release rates, with the F1 encapsulation (0.5% chitosan, 0.2% HAP) achieving a cumulative release of 78.3 ± 3.2% in contrast to 65.1 ± 2.7% for the F5 formulation (2.5% chitosan, 1% HAP). These encapsulations selectively modulated the overproduction of proinflammatory cytokines, including IL‐1β, IL‐6, and TNF‐α, in gingival fibroblasts and osteoblasts without compromising cell viability. An artificial neural network (ANN) model accurately forecasted the material properties and biological performance of the formulations based on their compositional variations, yielding correlation coefficients exceeding 0.97. This computational platform offers a virtual screening tool for refining regenerative and drug delivery therapies. The developed chitosan‐hydroxyapatite microparticulate system demonstrates promising potential for prolonged treatment of periodontitis through controlled antibiotic delivery, improved mechanical properties, and targeted regulation of the inflammatory response.

Optimizing the synthesis conditions of CaAl‐layered double hydroxide and poly (3‐hydroxybutyrate)/CaAl‐LDH nanocomposite for potential use in antibacterial drug delivery

AbstractCalcium aluminum layered double hydroxide (CaAl‐LDH) has gained significance for drug delivery applications due to its multiple advantages, including high drug‐loading capacity, pH sensitivity, biocompatibility, high acceptable intake values of metal ions, and its ability to provide sustained release of the intercalated drug. In this study, pristine CaAl‐LDH was synthesized by co‐precipitation method at different pH values (9 and 10) and aging times (16 and 24 h) to obtain LDH with higher d‐spacing, which is beneficial for achieving a high drug loading efficiency. Ofloxacin (OFX), an antibiotic drug, was loaded into CaAl‐LDH via regeneration (CaAl‐LDH‐OFX(RG)) and co‐precipitation (CaAl‐LDH‐OFX(CPT)) methods, and achieved drug loading of 28.3% and 36.5%, respectively. The release behavior of OFX from CaAl‐LDH‐OFX(RG) and CaAl‐LDH‐OFX(CPT) formulations was examined in simulated conditions representing the gastrointestinal tract. CaAl‐LDH‐OFX(RG) showed less initial burst release of OFX compared to CaAl‐LDH‐OFX(CPT) in acidic as well as neutral pH conditions. In order to overcome the degradation of the drug before reaching the target site, CaAl‐LDH‐OFX(RG) was reinforced at 1, 3, and 5 wt% in poly (3‐hydroxybutyrate) (PHB) matrix by sonication‐assisted solution casting method. The PHB‐based nanocomposites were characterized by XRD, FESEM, TGA, and FTIR analyses. FESEM characterization of PHB‐based films loaded with 3 wt% of CaAl‐LDH‐OFX(RG) revealed compact morphology without any aggregate formation. Moreover, PHB/3CaAl‐LDH‐OFX(RG) films demonstrated sustained release of OFX at pH 1.2 (95.60% in 96 h), pH 6.8 (78% in 113 h), and pH 7.4 (40.90% in 107 h). The promising potential of PHB‐based formulations for antibacterial drug delivery systems was confirmed by their significant antibacterial activity against Escherichia coli and Staphylococcus aureus.Highlights pH and aging time influence the structural characteristics of pristine CaAl‐LDH. Ofloxacin loaded CaAl‐LDH prepared by co‐precipitation and regeneration methods. Sustained release of ofloxacin from poly (3‐hydroxybutyrate)‐based formulation. Poly (3‐hydroxybutyrate)‐based formulations exhibit excellent antibacterial activity.

Ethosuximide-loaded bismuth ferrite nanoparticles as a potential drug delivery system for the treatment of epilepsy disease.

Encapsulating antiepileptic drugs (AEDs), including ethosuximide (Etho), into nanoparticles shows promise in treating epilepsy. Nanomedicine may be the most significant contributor to addressing this issue. It presents several advantages compared to traditional drug delivery methods and is currently a prominent area of focus in cancer research. Incorporating Etho into bismuth ferrite (BFO) nanoparticles within diverse controlled drug delivery systems is explored to enhance drug efficacy. This approach is primarily desired to aid in targeted drug delivery to the brain's deepest regions while limiting transplacental permeability, reducing fetal exposure, and mitigating associated adverse effects. In this investigation, we explored Etho, an antiepileptic drug commonly employed for treating absence seizures, as the active ingredient in BFO nanoparticles at varying concentrations (10 and 15 mg). Characterization of the drug-containing BFO nanoparticles involved scanning electron microscopy (SEM) and elemental analysis. The thermal properties of the drug-containing BFO nanoparticles were evaluated via differential scanning calorimetry (DSC) analysis. Cytotoxicity evaluations using the MTT assay were conducted on all nanoparticles, and human neuroblastoma cell line cultures (SH-SY5Y) were treated with each particle over multiple time intervals. Cell viability remained at 135% after 7 days when exposed to 15 mg of Etho in BFO nanoparticles. Additionally, in vitro drug release kinetics for Etho revealed sustained release lasting up to 5 hours with a drug concentration of 15 mg.

Laser-responsive erastin-loaded chondroitin sulfate nanomedicine targeting CD44 and system xc− in liver cancer: A non-ferroptotic approach

Erastin, a ferroptosis-inducing system xc− inhibitor, faces clinical challenges due to suboptimal physicochemical and pharmacokinetic properties, as well as relatively low potency and off-target toxicity. Addressing these, we developed ECINs, a novel laser-responsive erastin-loaded nanomedicine utilizing indocyanine green (ICG)-grafted chondroitin sulfate A (CSA) derivatives. Our aim was to improve erastin's tumor targeting via CSA–CD44 interactions and enhance its antitumor efficacy through ICG's photothermal and photodynamic effects in the laser-on state while minimizing off-target effects in the laser-off state. ECINs, with their nanoscale size of 186.7 ± 1.1 nm and high erastin encapsulation efficiency of 93.0 ± 0.8%, showed excellent colloidal stability and sustained drug release up to 120 h. In vitro, ECINs demonstrated a mechanism of cancer cell inhibition via G1-phase cell cycle arrest, indicating a non-ferroptotic action. In vivo biodistribution studies in SK-HEP-1 xenograft mice revealed that ECINs significantly enhanced tumor distribution of erastin (1.9-fold greater than free erastin) while substantially reducing off-target accumulation in the lungs and spleen by 203-fold and 19.1-fold, respectively. Combined with laser irradiation, ECINs significantly decreased tumor size (2.6-fold, compared to free erastin; 2.4-fold, compared to ECINs without laser irradiation) with minimal systemic toxicity. This study highlights ECINs as a dual-modality approach for liver cancer treatment, demonstrating significant efficacy against tumors overexpressing CD44 and system xc−.

Quantum-Inspired Macromolecular Design: Harnessing Quantum Dots for Enhanced Polymer Functionality in Drug Delivery

Quantum dots (QDs) have emerged as transformative nanomaterials in drug delivery due to their unique optical and electronic properties, such as tunable fluorescence, high surface area and size-dependent emission in pharmaceutical origin. When integrated with polymers, this hybrid system offers enhanced functionality for targeted, controlled and stimuli-responsive drug delivery. This review focuses on the synthesis and application of quantum dot-polymer composites in drug delivery, emphasizing their ability to improve drug targeting, sustained release and real-time imaging in therapeutic applications. The multifunctionality of these systems enables personalized medicine approaches, particularly in cancer therapy and neurological disorders. Despite their promising potential, concerns related to toxicity and scalability pose significant challenges for their widespread clinical use. Ongoing research efforts are focused on developing more biocompatible QDs, optimizing the design of polymer-QD hybrids and addressing regulatory hurdles. This review, we believe, provides a comprehensive analysis of current advancements in quantum dot-based drug delivery systems and outlines future directions to overcome the existing limitations and enhance clinical applicability. The integration of quantum dots with polymers represents a significant leap forward in the field of nanomedicine, offering the potential for highly efficient, precise and safe drug delivery platforms.

Enhancement in the antibacterial activity of Rifaximin by delivery through gelatin nanoparticles

Objectives Bacterial infections are a noteworthy global health concern that necessitates the development of new strategies to enhance the potency and efficacy of antibiotics. Rifaximin (RFX), a broad-spectrum antibiotic, exhibits promising antibacterial activity against several bacterial strains. However, its insolubility and impermeability impede the exploitation of its full potential. The objective of the current study is to overcome the inherent caveats of RFX to exploit its maximum potential. Significance The exploitation of the full potential of antibiotics is necessary for reduction in their dosage and to minimize antibiotic pollution. This is a preliminary study aiming for maximum utilization of RFX at the target site and reduction in its release in unmetabolized form. Methods Gelatin is a biopolymer that has gained significant attention for biomedical applications owing to its inherent biocompatibility and biodegradability. In this study, bovine gelatin nanoparticles (BGNPs) were fabricated by the self-assembly method for their application as a carrier of RFX to enhance its antibacterial activity. The study employs a comprehensive range of experimental techniques to characterize the fabricated BGNPs such as DLS, Zeta Potential, FT-IR, AFM, SEM-EDX, and UV-Vis spectrophotometry. Results The average size of the fabricated BGNPs was 100 nm with a zeta potential value of −15.3 mV. The loading of RFX on BGNPs rendered an increase in its size to 136 nm with a zeta potential value of −16 mV. In-vitro assays and microscopic analyses were conducted to compare the antibacterial efficacy of RFX and RFX@BGNPs. An excellent loading capacity followed by sustained release of RFX from RFX@BGNPs rendered a significant enhancement in its pharmaceutical efficacy. The release of RFX from RFX@BGNPs followed the Higuchi and Korsmeyer-Peppas models. The antibacterial efficacy of RFX against Staphylococcus aureus has doubled by delivery through RFX@BGNPs, assessed by inhibitory and biofilm inhibitory assays. The enhancement in the antibacterial efficiency was further endorsed by SEM and microscopic imaging of the control and treated bacterial colonies. Conclusion The study demonstrates an enhancement in the antimicrobial efficacy of RFX by its delivery in the form of RFX@BGNPs to exploit its full potential for practical applications.

Synthesis and characterization of a novel dual sensitive iron nanoparticles incorporated Schiff base composite hydrogel for diabetic wound healing therapy

Chronic wounds in diabetic patients deteriorate into multiple infections. A multifunctional transdermal material with high self-healing ability, remodeling capability, antibacterial and radicle scavenging activity, and an excellent multi-sensitive carrier was needed to promote wound healing. For that, Oxidized Cellulose (OC) and gelatin (GLN) are selected to construct a dual drug-loaded Schiff base hydrogel with iron nanoparticle (IONPS) incorporation for the controlled and sustained release of Insulin (INS) and Metfomin (MET), which synergistically promote wound repair. The INS/MET-IONPS-OC/GLN hydrogel drug payload was characterized using FT-IR, XRD, DLS, ZETA, TG, FE-SEM, TEM, and VSM analysis. The high drug loading and encapsulation efficiency were 93.20 % and 98.8 % for INS and 90.2 % and 95.1 % for MET, respectively. The temperature-sensitive drug release (92.0 % of INS and 90.0 % of MET) percentage is much better than the pH-sensitive drug release (83.5 % of INS and 80.2 % of MET). Above 90.0 % viability in MTT and apoptosis assay reveals the nontoxic nature of the INS/MET-IONPS-OC/GLN towards L929 normal cell lines. The zone of inhibition value of 12 and 15 mm in gram-negative bacteria reveals the anti-bacterial effect. The antioxidant activity of the carrier shields the cells against reactive oxygen species promotes healing rate ensures by DPPH assay.The cell proliferation and angiogenesis were confirmed by scratch assay on L929 cell lines in diabetic and non-diabetic conditions, showing the healing ability of the INS/MET-IONPS-OC/GLN hydrogel.

Intra-articular injection of platinum nanozyme-loaded silk fibroin/pullulan hydrogels relieves osteoarthritis through ROS scavenging and ferroptosis suppression

Reactive oxygen species (ROS)-mediated ferroptosis plays a critical role in the development of osteoarthritis (OA). Consequently, it is speculated that anti-ferroptosis agents could represent a novel therapeutic strategy for managing OA. In this study, a hydrogel incorporating platinum (Pt) nanozyme was synthesized by dispersing Pt nanoparticles (NPs) within a matrix of silk fibroin (SF) and oxidized pullulan (oxPL). This hydrogel allows for a substantial and sustained release of up to 30 days. The gelation time (from 140.3 ± 42.3 s to 460.0 ± 40.0 s), swelling capacity (from 57.7 ± 3.8 % to 24.0 ± 7.0 %), and degradation rate (from 60.3 ± 4.7 % to 32.0 ± 4.6 %) of the hydrogels can be modulated by adjusting the Pt NP content. The Pt@SF/oxPL hydrogel effectively eliminates ROS due to its catalase-like and superoxide dismutase-like enzymatic properties. In vitro studies demonstrated that Pt@SF/oxPL efficiently mitigated the process of ferroptotic cell death in chondrocytes. More critically, intra-articular administration of Pt@SF/oxPL showcased therapeutic advantages by both protecting and stimulating the regeneration of cartilage throughout the progression of OA. Collectively, this study suggests that Pt@SF/oxPL hydrogels could potentially serve as an effective treatment for OA, presenting a novel nanozyme-based therapeutic approach for this condition.

Enhanced antidiabetic performance through optimized charantin-loaded nanostructured lipid carriers: Formulation and In vivo studies in diabetic mice

The hypoglycemic potential of charantin, a compound from Momordica charantia L., has been well-documented, but its pharmaceutical application faces challenges like poor solubility, low permeability, and suboptimal bioavailability. This study aimed to develop and optimize charantin-loaded nanostructured lipid carriers (Ch-NLCs) to enhance their antidiabetic efficacy. Using a 32 factorial design and high-pressure homogenization, Ch-NLCs were formulated with Precirol and Labrasol as solid and liquid lipids, respectively, combined with surfactants Tween 80 and Poloxamer 188. The optimization focused on key parameters such as particle size, entrapment efficiency (%EE), and zeta potential. FTIR confirmed the interaction between charantin and lipids, while DSC and XRD analyses showed the amorphous nature of Ch-NLCs. The optimized Ch-NLCs exhibited a particle size of 221.0 nm, an %EE of 81.89 %, and a zeta potential of −24.42 mV. In vitro release studies demonstrated a sustained release profile of charantin from the NLCs. In vivo studies on streptozotocin (STZ)-induced diabetic mice revealed significantly enhanced antidiabetic effects of Ch-NLCs compared to pure charantin. Specifically, Ch-NLCs led to substantial reductions in blood glucose levels, total cholesterol (T-Cho), low-density lipoprotein (LDL) and glycosylated hemoglobin (HbA1c) levels, while improving high-density lipoprotein (HDL). These findings highlight the potential of Ch-NLCs as an effective delivery system for charantin in diabetes management. In conclusion, the study successfully engineered and optimized Ch-NLCs, demonstrating their superior pharmacokinetic profiles over pure charantin. These results suggest that Ch-NLCs could be a promising candidate for effective diabetes management, warranting further clinical investigation to confirm their therapeutic potential in human subjects.

Controlled release of doxorubicin from Poly-(D,L-lactide-co-glycolide) (PLGA) nanoparticles prepared by coaxial electrospraying

Enhancing the efficacy and reducing the toxicity of chemotherapeutic agents like doxorubicin (DOX) is crucial in cancer treatment. Core-shell nanoparticles (NPs) fabricated by coaxial electrospraying offer controlled release of anticancer agents with the polymer shell protecting drug molecules from rapid degradation, prolonging therapeutic effect. This study developed DOX-loaded poly(lactic-co-glycolic acid) (PLGA) NPs. NPs were fabricated with matrix or core–shell structure via single needle or coaxial electrospraying, respectively. Core-shell NPs exhibited high encapsulation efficiency (>80 %) with controlled DOX distribution. Compared to matrix NPs, core–shell NPs demonstrated slower sustained release (69 % in 144 h) after reduced initial burst (22 % in 8 h). Release kinetics followed a diffusion mechanism when compared to free drug and matrix DOX-loaded NPs. In vitro assays showed core–shell NPs’ enhanced cytotoxicity against breast cancer cells MCF-7, with higher uptake observed by fluorescence microscopy and flow cytometry. The IC50 for core-shell NPs displayed a significant drop (0.115 μg/mL) compared to matrix NPs (0.235 μg/mL) and free DOX (1.482 μg/mL) after 72 h. Coaxial electrospraying enables the production of therapeutically advantageous core–shell NPs, offering controlled drug release with high encapsulation efficiency, potentially improving clinical anticancer chemotherapy.

Exploring the therapeutic applications of nano-therapy of encapsulated cisplatin and anthocyanin-loaded multiwalled carbon nanotubes coated with chitosan-conjugated folic acid in targeting breast and liver cancers

This study aimed to assess the targeted nano-therapy of encapsulated cisplatin (Cis) and anthocyanin (Ant)-loaded multiwalled carbon nanotubes (CNT) coated with chitosan conjugated folic acid on breast MCF7 and liver HepG2 cancer cells. Zeta potential, UV-spectroscopy, FTIR, TEM, and SEM were used to evaluate CNT, its modified form (CNT Mod), CNT-loaded Cis NPs, CNT-loaded Ant NPs, and CNT- Cis + Ant NPs. All treatments induced apoptosis-dependent cytotoxicity in both cell lines as revealed functionally by the MTT assay, morphologically (DNA degradation) by acridine orange/ethidium bromide (AO/EB) double staining, and molecularly (Bax upregulation and Bcl2 downregulation) by real-time PCR, with best effect for the combined treatment (CNT- Cis + Ant NPs). This combined treatment also significantly reduced inflammation (low TNFα), migration (low MMP9 and high TIMP1), and angiogenesis (low VEGF), while significantly increasing antioxidant status (high Nrf2 and OH-1) in MCF7 and HepG2 cells compared to other treatments. Interestingly, cells treated with CNT Mod exhibited higher cytotoxic, apoptotic, anti-migratory, and anti-angiogenic potentials relative to CNT-treated cells. In conclusion, targeted nano-therapy of encapsulated cisplatin and anthocyanin-loaded carbon nanotubes coated with chitosan conjugated folic acid can efficiently combat breast and liver cancers by sustained release, in addition to its apoptotic, antioxidant, anti-inflammatory, anti-metastatic, and anti-angiogenic effects.

Metal-free ring-opening polymerization for the synthesis of biocompatible star-shaped block copolymers with controllable architecture

Star-shaped block copolymers (SBCs) have sparked interest as efficient cargo carriers due to their high loading capacity, decreased burst effects through sustained release, and maintained stability in dilute aqueous solution. Despite these advantages, the practical usage of SBCs is hindered by their challenging synthesis processes that often utilize metal-based catalysts at high temperatures. Herein we report the tailored synthesis of 3-, 4-, and 6-arm polycaprolactone-b-poly(ethylene glycol), PCL-b-PEG, SBCs using diphenyl phosphate as a friendlier, more sustainable non-metallic catalyst. Nuclear magnetic resonance (NMR) analysis confirms the molecular architecture of SBCs and gel permeation chromatography (GPC) is used to elucidate trends in molar mass when the number of arms within the SBCs is tuned, while dynamic light scattering (DLS) and small-angle X-ray scattering (SAXS) studies provide insights into aggregation behavior. Critical aggregation concentration (CAC) values, as measured by fluorescence spectroscopy, demonstrated that the 4-arm and 6-arm SBCs have greater stability than the 3-arm SBC. Biocompatibility assessment indicated minimal cytotoxicity of the nanoaggregates, even at high concentration, making these PCL-b-PEG SBCs potentially safe and sustainable vehicles for biomedical release applications.

3D-printed controllable bio-accelerators with sustained release property to boost chromium (VI) inhibited denitrification recovery

Although soluble bio-accelerators have proven effective in mitigating Cr(VI) inhibition within denitrification system, issues persist in immobilizing bio-accelerators and making them slow-release for sustained regulation. In this study, a novel strategy was proposed to fabricate immobilized bio-accelerators with controlled structure, sustained release property by 3D printing technology. Notably, the sustained release of bio-accelerators from 3D-printed bio-accelerators (3DP-B) lasted for at least 144 h. Compared to control group, 3DP-B with basic components (3DP-BB) shortened the recovery time by 1.4 folds, and the COD and NO3--N removal efficiency was 36.5 % and 38.0 % higher than that of natural recovery. Correspondingly, the activity of key enzymes (nitrate reductase, nitrite reductase, nitric oxide reductase, and nitrous oxide reductase), electron transfer system activity and extracellular polymer substances of denitrification biofilm maintained at relatively high levels. Furthermore, introducing 60 mg·L-1 anthraquinone-2,6-disulfonate (AQDS) into the ink showed noticeable superiority on the bio-inhibition release over 1000 mg·L-1 AQDS. The released AQDS facilitated the electron transport capacity by 1.25 times compared with control group. The groundbreaking findings of this study could advance the development of 3D printing technology and utilization of bio-accelerators in the field of wastewater treatment.

PH-responsive acrylic resin for the sustained release and cellular imaging of rhodamine-nido-carborane fluorescent complexes

pH-responsive acrylic resin for the sustained release and cellular imaging of rhodamine-nido-carborane fluorescent complexes