Sustained Release System Research Articles

Nanosphere hydrogel-mediated delivery of miR-34a-5p improves achilles tendon function in rat model.

Restoring motor function and preventing re-rupture and adhesion during Achilles tendon healing remain significant clinical challenges. Increasing evidence suggests that miRNA plays a crucial role in tendon healing and regeneration. The previously designed nanosphere hydrogel sustained-release system enables targeted, controlled release of drugs. In this study, we developed a version of this system loaded with miR-34a-5p for localized delivery to an acute Achilles tendon injury model. The results of the Achilles functional index and Catwalk behavior analysis in rats indicated that miR-34a-5p mimic promoted early recovery of motor function following Achilles tendon injury. Although gross observation suggested that the miR-34a-5p mimic group had a minimal inhibitory effect on the adhesion of Achilles tendon tissue, tension analysis demonstrated that it effectively increased the maximum tensile strength. Additionally, in vitro experiments showed that miR-34a-5p mimic could increase tendon cells proliferation and improve tendon cells viability. This study confirmed the efficacy of the miR-34a-5p nanosphere hydrogel sustained-release system in tendon injury repair, presenting it as a promising treatment strategy for clinical practice.

DSPindex guides dose selection to extend drug supersaturation lifetime during cocrystal dissolution.

Synchronising both cocrystal dissolution and drug precipitation processes is the key for the development of cocrystal systems with desired dissolution-supersaturation-precipitation (DSP) behaviours. Our findings with ketoconazole (KTZ) - p-aminobenzoic acid (PABA) 1:1 cocrystal show that this can be achieved by generating non-stoichiometric coformer concentrations that allow us to modulate the maximum theoretical cocrystal supersaturation SA (thermodynamic limit) below the drug critical supersaturation σcrit (kinetic limit). The application of our conceptual graphical approach combined with the two metrics SA and the DSPindex answer the question of how much additional coformer is needed to target optimal sustained drug supersaturation levels. Modulating SA < σcrit and DSPindex > 1 allowed for a stable and sustained KTZ release system with supersaturation levels of 6 by 24 h. Findings provide a direct approach for better early decisions regarding cocrystal dose design and/or coformer concentration to be added to formulations to ultimately fine-tune drug supersaturation by coupling dissolution and precipitation processes.

Immunomodulation effects of collagen hydrogel encapsulating extracellular vesicles derived from calcium silicate stimulated-adipose mesenchymal stem cells for diabetic healing

Diabetic wounds are characterized by chronic inflammation, reduced angiogenesis, and insufficient collagen deposition, leading to impaired healing. Extracellular vesicles (EVs) derived from adipose-derived mesenchymal stem cells (ADSC) offer a promising cell-free therapeutic strategy, yet their efficacy and immunomodulation can be enhanced through bioactivation. In this study, we developed calcium silicate (CS)-stimulated ADSC-derived EVs (CSEV) incorporated into collagen hydrogels to create a sustained-release system for promoting diabetic wound healing. CSEV exhibited enhanced protein content, surface marker expression, and bioactive cargo enriched with pro-angiogenic and anti-inflammatory factors. In vitro, CSEV-loaded collagen significantly reduced reactive oxygen species production, promoted cell proliferation and migration compared to standard EV-loaded collagen. Cytokine profiling revealed the upregulation of anti-inflammatory cytokines and extracellular matrix components, highlighting their immunomodulatory and regenerative potential. In vivo, histological evaluation of diabetic rabbit models treated with CSEV-loaded collagen revealed superior reepithelialization and organized collagen deposition, indicating accelerated wound closure. These findings underscore the potential of CSEV-loaded collagen hydrogels as an innovative and effective therapeutic platform for enhancing diabetic wound healing by simultaneously addressing inflammation and tissue regeneration.Graphical abstract

A Comprehensive Review of Innovations for Diabetic Retinopathy and Next-generation Intraocular Drug Delivery

Diabetic Retinopathy (DR) is a significant cause of blindness worldwide, particularly in individuals with diabetes. Early diagnosis and intervention are critical in preventing vision loss. However, existing treatments, including anti-VEGF therapies and laser photocoagulation, present several challenges such as frequent injections, side effects, and difficulties in targeting the root causes of the disease. This systematic review examines the innovations in intraocular drug delivery systems for treating DR, focusing on advancements such as sustained-release implants, nanotechnology-based approaches, and gene therapy. These emerging technologies aim to overcome barriers like the blood-retinal barrier (BRB) and improve the efficacy of drug delivery to the retina. Sustained-release systems offer the potential for reducing injection frequency, while nanoparticles and liposomes enhance drug targeting and bioavailability. Gene therapy, which delivers therapeutic genes directly to retinal cells, represents a novel approach to addressing the underlying mechanisms of DR. Despite these promising developments, challenges remain, including improved drug targeting, patient compliance, and long-term safety. The review also highlights the need for interdisciplinary research and the integration of advanced technologies, such as artificial intelligence, in enhancing DR treatment. Future studies should optimise these drug delivery platforms, explore combination therapies, and develop personalised treatment strategies to improve patient outcomes. Overall, the next generation of drug delivery systems holds great promise in transforming the management of Diabetic Retinopathy and preventing its progression to vision-threatening stages.

Enhanced antitumor efficacy through sustained release of 5-fluorouracil from poly(trimethylene carbonate) membranes

IntroductionCancer remains one of the deadliest diseases worldwide. 5-Fluorouracil (5-FU) is one of the most commonly used chemotherapeutic agents in clinical practice today, but its effectiveness is often hampered by rapid drug metabolism and systemic toxicity. To address these limitations, the development of novel drug delivery systems for sustained drug release is essential to improve therapeutic outcomes.MethodsThis study aimed to develop a poly(trimethylene carbonate) (PTMC) membrane capable of sustained drug release of 5-FU to enhance its antitumor activity. The membranes were prepared using the solvent-casting method, and their comprehensive properties were characterized.Results and DiscussionWe evaluated the in vitro sustained release capability, as well as the biocompatibility and antitumor activity at both cellular and animal levels. The results demonstrated that the 5-FU-loaded PTMC membranes exhibited effective sustained release capabilities, superior biocompatibility, and enhanced antitumor effects compared to the 5-FU injections. These findings suggested that the 5-FU-loaded PTMC membranes hold great potential for application in cancer patients, offering benefits in chemotherapy treatment.

Core-shell hydrogel with synergistic super absorption and long-term acid resistance stability: a novel gastric retention drug delivery carrier.

Traditional natural polysaccharide-based hydrogels, when used as drug carriers, often struggle to maintain long-term stability in the extremely harsh gastric environment. This results in unstable drug release and significant challenges in bioavailability. To address this issue, this study utilized inexpensive and safe natural polysaccharides-chitosan (CS) and high methoxyl pectin (HM)-as raw materials. Dynamic chemical bonds and anion-cation electrostatic interactions were employed to successfully prepare a super absorbent gel bead substrate (CS-HM), which serves as the "core" structure. Subsequently, another low-density hydrophilic polysaccharide, sodium carboxymethyl cellulose (CMCNa), was used to coat and crosslink the outer layer of the core, increasing the number of ionic groups. This enhancement raises the osmotic pressure inside the gel network, improving its absorption capacity. At the same time, the core-shell structure provides an energy dissipation mechanism, allowing the material to remain more stable in a strong acid environment. Due to its super absorption, high modulus, and continuous floating release properties, CS-HM@CMCNa-as a new type of acid-resistant super absorbent core-shell material-possesses the key characteristics required for gastric retention sustained-release systems. It is expected to become an ideal drug carrier for the treatment of clinical chronic diseases.

Smart core-shell microneedles for psoriasis therapy: In situ self-assembly of calcium ion-coordinated dexamethasone hydrogel.

Psoriasis is a prevalent relapsing dermatological condition that often necessitates lifelong treatment. The distinctive thickening of the stratum corneum presents a challenge to drug penetration. The employment of microneedles has been demonstrated to enhance the transdermal drug delivery efficacy by creating multiple microchannels in the skin. Nevertheless, polymeric microneedles often encounter difficulties in meeting the requirements for sustained drug release. It is imperative to acknowledge that sustained-release hydrogel microneedles are invariably fabricated under harsh crosslinking conditions. In addressing these challenges, a core-shell microneedles (CSMNs) system was customized at a facile, accessible process, enabling the in situ formation of supramolecular microhydrogels within the skin. This concept was realized by leveraging the interaction between the therapeutic drug dexamethasone sodium phosphate (DexP) and calcium chloride (CaCl2), combined with the differential biphasic release technology (DexP HMNs). Upon insertion into the skin, the core of the microneedles rapidly released CaCl2, which diffused to the shell and formed a hydrogel with DexP, creating multiple reservoirs for the sustained release of DexP. In vitro transdermal permeation experiments demonstrated that DexP HMNs greatly prolonged the skin retention time of DexP. In the context of psoriasis treatment, DexP HMNs were demonstrated to be more effective than DexP CSMNs in inhibiting keratinocyte proliferation and significantly reducing the levels of inflammatory factors and immune cell infiltration at the lesion site. This study provides a new direction for the development of intelligent microneedle drug delivery systems for sustained drug release and enhanced management of chronic skin diseases.

Novel hybrid system based on carboxymethyl chitosan hydrogel encapsulating drug loaded nanoparticles for prolonged release of Vancomycin in the treatment of bacterial infection.

Current bacterial infections clinical treatments, such as intravenous antibiotic administration and local injection, suffer from short action duration, repeated administrations, and severe cell toxicity. To address these limitations, it is imperative to develop sustained drug release system with prolonged antimicrobial effects. In this work, a hybrid system was prepared using EDC/NHS catalyzed crosslinking-based carboxymethyl chitosan (CMCS) hydrogel as a carrier to encapsulate biodegradable nanoparticles (NPs) loaded with vancomycin, an efficient antibacterial drug. First, ring opening polymerization of L-lactide or L-lactide/glycolide mixture was performed in the presence of poly(ethylene glycol) (PEG) to yield PEG-PLA or PEG-PLGA block copolymers. Vancomycin was loaded in PEG-PLA or PEG-PLGA NPs using double emulsion method. Drug-loaded NPs were then encapsulated in the CMCS hydrogel. Drug release from NPs, CMCS hydrogel and hybrid NPs-hydrogel systems was performed, and release kinetics were analyzed using Korsmeyer-Peppas model. The established hybrid system exhibited prolonged drug release without burst release. Finally, the biocompatibility of the hybrid system was evidenced by the MTT, hemolysis, dynamic clotting time, and zebrafish embryotoxicity tests. Last but not least, the hybrid system displayed outstanding long-lasting antimicrobial activity as shown by co-culture with Monoclonal S. aureus, thus suggesting great potential for applications in bacterial infection treatment.

Convertible Hydrogel Injection Sequentially Regulates Diabetic Periodontitis.

Diabetes exacerbates periodontitis by overexpressing reactive oxygen species (ROS), which leads to periodontal bone resorption. Consequently, it is imperative to relieve inflammation and promote alveolar bone regeneration comprehensively for the development of diabetic periodontal treatment strategies. Furthermore, an orderly treatment to avoid interference between these two processes can achieve the optimal therapeutic effect. Thus, we constructed a sequential sustained release system based on the zeolitic imidazolate framework-8 (ZIF-8)-modified chitosan thermosensitive hydrogel (TOOTH) for diabetic periodontal therapy in this work. Chemically modified tetracycline-3 (CMT-3) and platelet-derived growth factor-BB (PDGF-BB) were loaded in the hydrogel and ZIF-8 for sequential release, respectively, with the aim of reducing inflammation and facilitating tissue regeneration. During the therapy, CMT-3 first escaped from the hydrogel due to degradation and diffusion for ROS elimination. Subsequently, ZIF-8 was dissociated under an acid microenvironment, and PDGF-BB was sustainably released to promote osteogenesis. The release intervals between CMT-3 and PDGF-BB could be regulated by the sizes of ZIF-8. The biocompatible TOOTH exhibited a favorable therapeutic effect for diabetic periodontitis in vitro and in vivo. The sequentially controlled release of CMT-3 and PDGF-BB facilitated by TOOTH holds promise for promoting periodontal tissue regeneration and offers potential for clinical translation.

In Vitro Evaluation of Niosomal Formulation for Controlled Delivery of 4‐Hydroxyisoleucine

AbstractThe development of drug delivery systems has aimed to improve bioavailability and reduce limitations of traditional dosing schedules. Vesicular systems like niosomes have gained importance for their stability, cost‐effectiveness, and controlled release capabilities. Niosomes can encapsulate both hydrophobic and hydrophilic drugs, making them versatile carriers for various therapeutic agents. Recent research focuses on enhancing niosomes for targeted drug delivery, such as incorporating 4‐hydroxyisoleucine (4‐HIL) for diabetes treatment. In this study, 4‐HIL from fenugreek seeds was encapsulated in niosomes and PEGylated niosomes using a thin‐film hydration method. The 4‐HIL‐loaded niosomes showed semi‐spherical, smooth structures with a size of 200 nm, zeta potential of ‐22 mV, and entrapment efficiency ranging from 55.1% to 87.1%. FTIR spectroscopy confirmed hydrogen bonding between span 60 and cholesterol in the niosomal formulation. PEGylation increased vesicle size to 460–580 nm and enhanced encapsulation efficiency to 75.43–90.1%. The PEGylated niosomes significantly suppressed the in vitro release of 4‐HIL, making this formulation a promising drug delivery system for sustained release of anti‐diabetic drugs.

A novel sustained-release agent based on disulfide-induced recombinant collagen hydrogels for the prevention and treatment of Schistosoma infections.

Schistosomiasis is commonly managed using the praziquantel, but it is only effective against adult worms and duration of action is short. Liver fibrosis will worsen if eggs are still present after stopping treatment. Therefore, this study aimed to develop a sustained drug release system for effectively preventing and treating schistosomiasis. A disulfide bond-induced three-dimensional (3D) recombinant collagen hydrogel was developed for sustained praziquantel release. Three collagen sequences were developed based on the sequence for Scl2 of S. pyogene, with different substitutions of residues for cysteine (S-VCL-S1, S-VCL-S2, and S-VCL-S3). Their properties were tested. Mice were infected with Schistosoma japonicum cercariae and treated either with praziquantel collagen hydrogel or niclosamide collagen hydrogel. The worm-killing effect was examined. The application of hydrogel-niclosamide on the skin for 24 h effectively prevented Schistosome cercariae from infecting mice and showed 70.95% and 81.73% reduction in the number of eggs and worms, respectively. The combined use of niclosamide and anti-cercariae cream showed 100% protection after 24 h. The hydrogel-praziquantel also showed a 100% reduction of worms and eggs after 24 h of subcutaneous injection. The subcutaneous injection of praziquantel after 28 days of infection showed 95.19% and 80.12% reduction of worm and egg counts, respectively, and the development of larvae was significantly slowed down. Liver analysis showed no infection after 7 days of treatment. These results suggest developing a novel type of sustained-release agent against schistosomiasis based on the recombinant collagen hydrogel that provides a potential new treatment for schistosomiasis.IMPORTANCEThis study introduces an new way for treating schistosomiasis: a special collagen hydrogel that gradually releases medication to treat schistosomiasis effectively. This innovation provides a promising way to treat schistosomiasis. It represents a significant step forward in the fight against this disease and offers hope for more effective and safer treatments in the future.

A Review on Role of Sustained Release Tablets in Improving Patient Compliance and Therapeutic Outcomes

Sustained release tablets represent a significant advancement in pharmaceutical drug delivery, offering controlled and prolonged release of active ingredients to enhance therapeutic outcomes. This novel approach addresses the limitations of conventional dosage forms by maintaining consistent plasma drug levels, reducing dosing frequency, and improving patient compliance. Sustained release systems utilize various technologies, including matrix systems, reservoir systems, and osmotic pumps, to regulate drug release over an extended period. This review provides a comprehensive analysis of the design, formulation strategies, and evaluation techniques for sustained release tablets. It highlights their applications in managing chronic diseases, improving bioavailability, and minimizing side effects. The potential challenges, such as variability in gastrointestinal conditions and cost- effectiveness, are also discussed. By integrating sustained release technology into holistic health management, this approach contributes to more effective, patient-centered therapies. Keywords-Sustained Release Tablets, Controlled Drug Delivery, Prolonged Release, Matrix Systems, Osmotic Pumps

Synthesis of a PVA-GO drug delivery system for sustained release of 4-methyl umbelliferon

Introduction 4-methyl umbelliferon (4MU) is a coumarin with anti-inflammatory, anti-thrombotic, enzyme-inhibiting, and antioxidant properties. Despite the benefits of the compound, it is eliminated very quickly from the blood circulation through the liver, kidney, and digestive system due to its hydrophobic properties. In this study we proposed to improve the durability of 4MU by binding of 4MU to poly vinyl alcohol (PVA) and graphene oxide (GO). Methods The PVA-4MU-GO complex was synthesized and characterized. Release of 4MU from the complex was investigated. H9C2 cells viability was investigated and the entry of complex to the cell was analyzed using flow cytometry. Result UV-Vis and FTIR studies confirmed the interaction of 4MU with PVA and GO. SEM measurement also revealed a particle size around 101 nm for PVA-4MU-GO complexes. The obtained results confirmed the assembly of PVA-4MU-GO. A continuous drug release for 8 d (160 h) was achieved. Cytotoxic studies on H9C2 cell showed that PVA-4MU-GO complex is dependent to the concentration of GO and also the relation of 4MU to GO. Sustained release and penetration of PVA-4MU-GO complex into the H9C2 cell were observed. Conclusion PVA-4MU-GO complex is recommended as an alternative for 4MU. Synthesis the complex of PVA-4MU-GO, verifying the correct binding, showing the in vitro release of the 4MU, as well as checking its toxicity and its gradual entry into the H9C2 cell, were performed in this study.

Development and evaluation of a liposome hydrogel system for enhanced delivery of drospirenone at higher doses.

Drospirenone (DROP) is a highly effective, low-toxicity, safe new generation progestin that counteracts estrogen-related sodium retention, is well tolerated, and has a positive effect on premenstrual syndrome (PMS). However, the low water solubility of DROP and its chemical instability resulted in low bioavailability. In this study, we developed a two-step delivery system to enhance drospirenone's solubility and stability. We prepared a drospirenone liposome complex to optimize the encapsulation process and achieve an encapsulation efficiency of (84.9 ± 0.73) %, with an 878-fold increase in solubility under optimal conditions. To address the instability of high drug-loading liposomes, we immobilized the drospirenone liposome inclusion complex using a cellulose-based hydrogel. The system achieved uniform loading of liposomes in the hydrogel, as confirmed by SEM and FTIR analysis. 0.5g hydrogel can be loaded with up to 96.48mg drospirenone, and the encapsulation efficiency is (80.4 ± 1.17%). It was indicating the potential for wider application of drospirenone with enhanced water solubility and improved stability. At the same time, it also provides support for sustained-release systems or large dose drug delivery.

Novel double-layered PLGA microparticles-dissolving microneedle (MPs-DMN) system for peptide drugs sustained release by transdermal delivery.

The combination of microparticles (MPs) with dissolving microneedles (DMN) represents a promising transdermal approach for the sustained release of biomacromolecule drug. In this study, we developed a double-layered microparticles-dissolving microneedle (MPs-DMN) system, which strategically concentrates PLGA MPs at the tip of the microneedle to achieve sustained release of peptide drugs through transdermal delivery. We selected exenatide (EXT) as a model peptide drug and established HPLC-UV and UPLC-MS methods for the quantitative analysis of the drug content of MPs-DMN and drug concentrations in plasma. Ultrasonication was utilized in the first step of the double emulsion solvent evaporation method to produce PLGA microparticles, achieving a high drug loading efficiency of 22.76 ± 0.64 %, surpassing the commercial products. The EXT-loaded microparticles were then mixed with 10 % w/v sucrose solution to form the first layer of the microneedle, and the mixture of the base solution was added to form the double-layered dissolving microneedle. Microscopic analysis revealed that the MPs were predominantly concentrated in the upper 50 % of the microneedle body, resulting in an impressive drug delivery efficiency of 92.86 ± 1.62 %. The MPs-DMN patch demonstrated the capability to 238.20 ± 5.79 μg of EXT within a compact area of 0.75 cm2, surpassing the capacities reported in existing research. The insertion and dissolution assessments exhibited rapid dissolution, maintaining the MPs as an effective drug reservoir within the skin. Pharmacokinetic assessments indicated that the long half-life (T1/2) of 466.4 ± 12.2 h and high relative bioavailability of 89.71 % for MPs-DMN. Furthermore, pharmacodynamic studies indicated that the MPs-DMN effectively controlled blood glucose levels below 20 mmol/L in diabetic (db/db) mouse for two weeks. These promising findings suggest that the MPs-DMN system could serve as a viable transdermal delivery method for the prolonged administration of peptide drugs.

Innovative ocular drug delivery systems: A comprehensive review of nano formulations and future directions

The eye's intricate structure and blood-ocular barriers pose significant challenges to effective ocular drug delivery. The blood-retinal barrier and blood-aqueous barrier restrict drug penetration, leading to poor bioavailability and limited treatment options for ocular diseases. Various administration routes, including systemic, topical, intravitreal, subconjunctival, and intracameral, have been explored to overcome these barriers. Nanotechnology-based platforms, such as liposomes, nanoemulsions, nanomicelles, nanosuspensions, and niosomes, have shown promise in enhancing ocular drug delivery. These platforms offer improved solubility, stability, and targeted release, increasing the efficacy of treatments for conditions like age-related macular degeneration, cataracts, diabetic retinopathy, fungal keratitis, and retinoblastoma. Future perspectives focus on developing minimally invasive, sustained-release systems that maintain intraocular efficacy. Nanofibers and stimuli-responsive drug delivery systems also hold potential for overcoming ocular delivery challenges.

Fabrication of hydrogel matrix for controlled release of ropivacaine for long-acting local anesthetic treatment in postoperative pain management

Local anesthetics have been used for temporary loss of pain, which limits their clinical application due to the neurotoxicity and short half-lives. In this present investigation, we have developed a novel k-carrageenan/alginate (k-CN/AGT) hydrogel loaded with Ropivacaine (RVN) to achieve a sustained release system. The synthesized k-CN/AGT hydrogels were examined for structural characterization, morphology, and mechanical properties. The observed studies revealed hydrogel has a suitable porous structure (0.5 to 5 µm) and effective swelling ratio with controlled in vitro release kinetics. The in vitro biocompatibility test on human dermal fibroblast cells confirmed that hydrogel has a nontoxic nature. The anesthetic activity of k-CN/AGT-RVN hydrogels was evaluated in vivo and compared with commercial formulations. Ex vivo permeation efficiency of k-CN/AGT-RVN hydrogels surpassed that of the RVN. As a result, the study demonstrated that k-CN/AGT-RVN hydrogels have the potential to prolong the effects of local anesthesia, offering a promising avenue for effective pain management.

Iron (hydr)oxide minerals-microbe interaction associated retention capacity boost and reaction rate fluctuation for perfluorooctanoic acid in an in-situ iron-based and microbe-based sustained-release system

Based on the inefficient elimination of emerging contaminant perfluorooctanoic acid (PFOA) and the unpredictable performance of the filed-scale system, a novel in-situ iron-based and microbe-based sustained-release system and filed-scale model were developed to address the above issues in this study.Especially, the PFOA-microbe-mineral interaction in various types of groundwater and the relevant mechanism were quantitatively and deeply studied. The results showed that the sustained-release interaction system in HCO3− type groundwater exhibited a greater retardation effect (Kd = 0.73 cm3 g−1) on PFOA compared to the interaction system under no ions condition (Kd = 0.49 cm3 g−1) or microbe system (Kd = 0.43 cm3 g−1). Moreover, the reaction rate λ of PFOA exhibited minimal fluctuation in HCO3− type groundwater, indicating lower competition from HCO3− ions for occupancy site and resulting in less PFOA repulsed to the lower reactive region (with lower Fe2+ and microorganism cells concentrations). Furthermore, the retardation effect for PFOA was boosted by secondary minerals-microbe interaction and joint adsorption. HCO3− facilitated the minerals-microbes interaction, leading to increased formation of β-FeOOH and improved retardation effect for PFOA. Additionally, the functional microorganisms Pseudomonas and Delftia were combined to drive the Fe3+/Fe2+ cycle and PFOA biochemical transformation. The two-dimensional spatiotemporal evolution simulation results showed that pollutant flux (transport risk) of PFOA in HCO3− type groundwater system (0.124 × 10−3 mg·(m2·s)−1) can be reduced by 23.0% compared to that in NO3− type groundwater system (0.161 × 10−3 mg·(m2·s)−1). This study quantitatively revealed the coupling effect of minerals, microbes, and ions on PFOA, contributing to optimizing the sustained-release system for effectively remediating different types of PFOA-contaminated groundwater.

An injectable carboxymethyl chitosan-based hydrogel with controlled release of BMP-2 for efficient treatment of bone defects

Although biological scaffolds containing bone morphogenetic protein-2 (BMP-2) have been widely used for osteogenic therapy, achieving stable and controlled release of BMP-2 remains a challenge. Herein, a novel BMP-2 sustained-release system composed of carboxymethyl chitosan (CMCS)/polyethylene glycol (PEG)/heparin sulfate (HS) (CMCS/PEG/HS) was constructed with a Schiff base reaction, yielding an injectable hydrogel for the release of BMP-2 in a controlled manner. For the CMCS/PEG/HS/BMP-2 hydrogel, the HS component had a negatively charged structure, which can bind to positively charged growth factors and prevent early hydrolytic metabolism of growth factors, thus achieving sustainable release of BMP-2. Notably, the release of BMP-2 in hydrogels was dependent mainly on degradation of the hydrogel matrix rather than simple diffusion. Generally, the CMCS/PEG/HS/BMP-2 hydrogel scaffold demonstrated excellent recoverability, good injectability, excellent biocompatibility and high adaptability, as well as efficient self-healing features to occupy irregularly shaped bone marrow cavities. The in vitro results revealed that the CMCS/PEG/HS/BMP-2 hydrogel promoted the osteogenic differentiation of MC3T3-E1 cells. Furthermore, the in vivo results suggest that the hydrogel has promising osteogenic effects that promote bone regeneration in a skull bone defect model. The injectable hydrogel scaffold shows great promise for bone treatment in the future.

Clarithromycin-tailored cubosome: A sustained release oral nano platform for evaluating antibacterial, anti-biofilm, anti-inflammatory, anti-liver cancer, biocompatibility, ex-vivo and in-vivo studies

The clinical implication of clarithromycin (CLT) is compromised owing to its poor solubility and, subsequently, bioavailability, unpalatable taste, rapid metabolism, short half-life, frequent dosing, and adverse effects. The present investigation provides an innovative sustained-release oral drug delivery strategy that tackles these challenges. Accordingly, CLT was loaded into a cubosome, a vesicular system with a bicontinuous cubic structure that promotes solubility and bioavailability, provides a sustained release system combating short half-life and adverse effects, masks unpleasant taste, and protects the drug from destruction in gastrointestinal tract (GIT). Nine various formulas were fabricated using the emulsification method. The resulting vesicles increased the encapsulation efficiency (EE %) from 57.64 ± 0.04 % to 96.80 ± 1.50 %, the particle size (PS) from 147.30 ± 21.77 nm to 216.61 ± 5.37 nm, and the polydispersity index (PDI) values ranged from 0.117 ± 0.024 to 0.278 ± 0.073. The zeta potential (ZP) changed from −20.65 ± 2.01 mV to −33.98 ± 2.60 mV. Further, the release profile exhibited a dual release pattern within 24 h., with the percentage of cumulative release (CR %) expanding from 30.06 ± 0.42 % to 98.49 ± 2.88 %, optimized formula was found to be CC9 with EE % = 96.80 ± 1.50 %, PS = 216.61 ± 5.37 nm, ZP = −33.98 ± 2.60 mV, PDI = 0.117 ± 0.024, CR % = 98.49 ± 2.88 % and IC50 of 0.74 ± 0.19 µg/mL against HepG-2 cells with scattered unilamellar cubic non-agglomerated vesicles. Additionally, it exhibited higher anti-MRSA biofilm, relative bioavailability (2.8 fold), and anti-inflammatory and antimicrobial capacity against Pseudomonas aeruginosa, Escherichia coli, Bacillus subtilis, and Staphylococcus aureus compared to free CLT. Our data demonstrate that cubosome is a powerful nanocarrier for oral delivery of CLT, boosting its biological impacts and pharmacokinetic profile.