Slow Drug Release Research Articles

Evaluation of Osteogenic Potential of Fucoidan Containing Chitosan Hydrogel in the Treatment of Periodontal Intra-Bony Defects-A Randomized Clinical Trial.

Periodontal diseases significantly impact about half of the global population, and their treatment often encompasses relieving symptoms as well as regenerating the destroyed tissues. Revolutionary research in the management of periodontal disease includes biomaterials, a boon to re-generative dentistry owing to their excellent biological properties: non-toxicity, anti-inflammatory, biocompatibility, biodegradability, and adhesion. This study aimed to fabricate an injectable fucoidan containing chitosan hydrogel and prove its effectiveness in periodontal bone regeneration. The injectable hydrogel was prepared using the sol-gel method and was subjected to various physical, chemical, and biological characterizations to understand its efficacy in formation of new bone. The effectiveness of the developed hydrogel was assessed in periodontal bony defects to study the soft and hard tissue changes. A total of 40 periodontitis patients with bony defects were recruited and randomized into two groups to receive fucoidan-chitosan hydrogel and concentrated growth factor, respectively. Customized acrylic stents were used to guide the hydrogel placement into the defect site. Post-surgical changes in clinical parameters were assessed at 3, 6, and 9 months to appreciate the soft and hard tissue changes using repeated measures analysis of variance and Bonferroni's post hoc test. Significance was kept at 5%. The porosity, water uptake of the prepared hydrogel showed good efficacy, with particle size of the fucoidan containing chitosan hydrogel of 6.000 nm. The MG-63 osteoblasts cell line revealed biocompatibility, biodegradability and showed slow and sustained drug release, increased cell proliferation, and enhanced alkaline phosphatase secretion. Mineralization assay was greatest in the fucoidan containing chitosan hydrogel. Clinically, it exhibited significantly lower probing depth values and a higher mean improvement in clinical attachment level as compared to the concentrated growth factor (CGF) group at the end of 3 and 6 months (p < 0.05). The mean of the defect fills in the fucoidan containing chitosan group was 1.20 at the end of 9 months (p < 0.001) as compared with defect fills observed in the CGF group. The presence of fucoidan in the hydrogel significantly contributed to bone regeneration in humans, thus strengthening its potential in tissue engineering. Fucoidan-chitosan will be a promising biomaterial for bone tissue regeneration.

Microfluidics-based PLGA nanoparticles of ratiometric multidrug: From encapsulation and release rates to cytotoxicity in human lens epithelial cells

Multidrug nanomedicine is an effective therapeutic approach for the treatment of chronic diseases and cancers. However, co-encapsulation and release of drug combination at a fixed ratio by nanoparticles, particularly for long acting ocular formulations, remains challenging. Herein, poly (lactic-co-glycolic acid) nanoparticles ratiometrically co-encapsulating hydrophilic dual drugs, mitomycin C and doxorubicin, was obtained (D/M PLGANPs) by combining microfluidics and the Design of Experiments approaches. The formulation variable of lactide-to-glycolide ratios (L/G 50:50, 75:15 and 85:15) was used to achieve fast, medium and slow drug release rates of D/M PLGANPs. The dissolution of D/M PLGANPs in simulated intraocular fluid exhibited sustained release of dual drugs at the fixed ratio over 7 days, and analysis using the Korsmeyer-Peppas model showed mechanism of drug release to be governed by diffusion. More importantly, in human lens epithelial cells, the drug release rate was negatively correlated with drug potency. The slower drug release from D/M PLGANPs led to lower efficacy of drug combination against pathogenesis of cellular migration and proliferation, the key pathogenic processes of capsular opacification after cataract surgery. Compared to fast (L/G 50:50) and medium (L/G 75:15) drug release rate of D/M PLGANPs, the slow release formulation (L/G 85:15) exhibited the least cellular uptake of the dual drugs and the ratio of drug combination was not maintained intracellularly. The present study implicates the potential of using microfluidics for synthesizing polymeric nanoparticles of ratiometric drug combination and highlights the drug release rate as the critical determinant of efficacy for the long-acting nanomedicine design.

A Sustained-Release Nanosystem with MRSA Biofilm-Dispersing and -Eradicating Abilities Accelerates Diabetic Ulcer Healing.

Drug-resistant bacterial infections and biofilm formation play important roles in the pathogenesis of diabetic refractory wounds. Tea tree oil (TTO) exhibits antimicrobial, antimycotic, and antiviral activities, especially against common clinically resistant strains, such as methicillin-resistant Staphylococcus aureus (MRSA), making it a potential natural antimicrobial for the treatment of acute and chronic wounds. However, TTO is insoluble in water, volatile, light-sensitive, and cytotoxic. While previous macroscopic studies have focused on sterilization with TTO, none have sought to alter its structure or combine it with other materials to achieve sustained release. Electrospun TTO nanoliposomes (TTO-NLs), arranged linearly via high-pressure homogenization, could stabilize the structure and performance of TTO to achieve slow drug release. Herein, we established a composite nano-sustained release system, TTO-NL/polyvinyl alcohol/chitosan (TTO-NL@PCS), using high-voltage electrospinning. Compared with the control, TTO-NL@PCS exhibits higher concentrations of the active TTO drug components, terpinen-4-ol and 1,8-cineole. Owing to its increased stability and slow release, early exposure to TTO-NL@PCS increases the abundance of reactive oxygen species in vitro, ultimately causing the biofilm to disperse and completely killing MRSA without inducing cytotoxic effects to the host. Moreover, in BKS-Leprem2Cd479/Gpt mice with a whole-layer skin infection, untargeted metabolomics analysis of wound exudates reveals upregulated PGF2α/FP receptor signaling and interleukin (IL)-1β and IL-6 expression following application of the composite system. The composite also ameliorates the chemotaxis disorder in early treatment and attenuates the wound inflammatory response during the repair stage of diabetic inflammatory wounds, and upregulates VEGF expression in the wound bed. TTO-NL@PCS demonstrates the remarkable potential for accelerating diabetic and MRSA-infected wound healing.

Paclitaxel-lipid prodrug liposomes for improved drug delivery and breast carcinoma therapy

Paclitaxel (PTX) is widely applied for the treatment of unresectable and metastasis breast carcinoma as well as other cancers, whereas its efficacy is always impeded by poor solubility. Liposomes are one kind of the most successful drug carriers which are capable of solubilizing PTX and improving patients’ tolerance owing to excellent biocompatibility and biodegradability. However, poor compatibility between PTX and liposomes compromises the stability, drug loading and anti-tumor capacity of liposomal formulations. To address this issue, three lipids with various chain lengths, namely, myristic acid (MA, 14C), palmitic acid (PA, 16C) and stearic acid (SA, 18C), were conjugated to PTX via ester bonds and the synthesized prodrugs with high lipophilicity were further formulated into liposomes, respectively. All liposomes show high stability and drug loadings, as well as sustained drug release. The chain lengths of lipids are negatively correlated with drug release and enzymatic conversion rates, which further impact the pharmacokinetics, tumor accumulation, and anti-tumor efficacy of liposomal PTX. Neither rapid nor slow drug release facilitates high tumor accumulation as well as anti-tumor efficacy of PTX. Among all liposomes, PTX-PA-loaded liposomes show the longest circulation and highest tumor accumulation of PTX and exert the most potent anti-tumor capacities in vivo, owing to its moderate drug release and enzymatic conversion rate. Witnessing its superior safety, PTX-PA liposomes hold potential for further clinical translation.

Formulation and in vitro evaluation of compression coated mebeverine HCl tablets for colon targeting

The aim of the study was to develop colon targeted compression coated Mebeverine HCl (MEB) tablets using pH dependent, swellable and rupturable polymers for effective treatment of irritable bowel syndrome (IBS). The MEB loaded core tablets were prepared by direct compression method using CCM and CP as super disintegrating agents at different concentrations and evaluated for pre compression and post compression parameters. The optimized core tablets were further used to fabricate compression coated tablets using different ratios of Eudragit L100, Eudragit S100 as pH- dependent polymers, Keltone and Ethocel as swellable and rupturable polymers by modified compression method. Drug compatibility with excipients was checked by FTIR studies and results indicate no interaction. The precompression and post compression studies were within acceptable limits. In vitro dissolution studies were done for compression coated tablets to find out the lag phase, burst drug release and retard drug release The findings of this study concludes that the lag time of compression coated tablet can be modulated by combining with EL 100, ES 100, Keltone and Ethocel in different weight ratio. These designed tablet system was found to be satisfactory in terms of release of the drug after the predetermined lag time, thus the system can be target to release in the colon proximity. The compression coating technique can be successfully applied for MEB for colon targeting to treat IBS.

Glucose-Triggered Release of trans-N-p-Coumaroyltyramine from Zeolitic Imidazolate Framework-8 (ZIF8) Modified with Dioscorea opposita Thunb Polysaccharide.

A Dioscorea opposita Thunb polysaccharide (DOP)-modified ZIF8 material was developed in this study, which can be used as a "smart" glucose-responsive carrier to control the slow release of drugs. The 3-aminophenylboronic acid (APBA) functionalized carboxylated long-chain polymer poly(ethylene glycol) (PEG) segments, which were first modified on the surface of ZIF8 nanoparticles with a hydrogen bond and then chemically cross-linked with DOP through a borate ester bond, leading to the drugs loaded on ZIF8 being "closed" in PBS but being "open" via taking off the DOP coating in high concentrations of glucose; thus, leakage can be prevented in the drug loaded and a glucose-triggered release can effectively result. Moreover, the materials showed good biocompatibility and the released trans-N-p-coumaroyltyramine (NCT) could work synergistically with the DOP to improve insulin resistance and promote glucose consumption in insulin-resistant HepG2 cells.

Multi-scale, multi-level anisotropic silk fibroin/metformin scaffolds for repair of peripheral nerve injury

Silk fibroin (SF) as a natural polymer has a long history of application in various regenerative medicine fields, but there are still many shortcomings in silk fibroin for using as nerve scaffolds, which limit its clinical application in peripheral nerve regeneration (PNR). In this work, a multi-scale and multi-level metformin (MF)-loaded silk fibroin scaffold with anisotropic micro-nano composite topology was prepared by micromolding electrospinning for accelerating PNR. The scaffolds were characterized for morphology, wettability, mechanical properties, degradability, and drug release, and Schwann cells (SCs) and dorsal root ganglia (DRG) were cultured on the scaffolds to assess their effects on neural cell behavior. Finally, the gene expression differences of neural cells cultured on scaffolds were analyzed by gene sequencing and RT-qPCR to explore the possible signaling pathways and mechanisms. The results showed that the scaffolds had excellent mechanical properties and hydrophilicity, slow degradation rate and drug release rate, which were enough to support the repair of peripheral nerve injury for a long time. In Vitro cell experiments showed that the scaffolds could significantly promote the orientation of SCs and axons extension of DRG. Gene sequencing and RT-qPCR revealed that the scaffolds could up-regulate the expression of genes related to SCs proliferation, adhesion, migration, and myelination. In summary, the scaffolds hold great potential for promoting PNR at the micro/nano multiscale and physical/chemical levels and show promising application for the treatment of peripheral nerve injury in the future.

Generating porous metal surfaces as a mean to incorporate thymol-loaded nanoparticles

Porous metals have gained interest in many fields such as biomedicine, electronics, and energy. Despite the many benefits that these structures may offer, one of the major challenges in utilizing porous metals is to incorporate active compounds, either small molecules or macromolecules, on these surfaces. Coatings that contain active molecules have previously been used for biomedical applications to enable the slow release of drugs, e.g., with drug-eluting cardiovascular stents. However, direct deposition of organic materials on metals by coatings is very difficult due to the challenge of obtaining uniform coatings, as well as issues related to layer adherence and mechanical stability. Our study describes an optimization of a production process of different porous metals, aluminum, gold, and titanium, using wet-etching. Pertinent physicochemical measurements were carried out to characterize the porous surfaces. Following the production of porous metal surface, a new methodology for incorporating active materials onto the metals by using mechanical entrapment of polymeric nanoparticles in metal pores was developed. To demonstrate our concept of active material incorporation, we produced an odor-releasing metal object with embedded particles loaded with thymol, an odoriferous molecule. Polymer particles were placed inside nanopores in a 3D-printed titanium ring. Chemical analysis, followed by smell tests, indicated that the smell intensity lasts significantly longer in the porous material containing the nanoparticles, compared with the free thymol.

Methotrexate and sulforaphane loaded PBA-G5-PAMAM dendrimers as a combination therapy for anti-inflammatory response in an intra-articular joint arthritic animal model

L-sulforaphane (LSF), a natural product developed from cruciferous vegetables, have shown potent anti-inflammatory effect in cancer as well as arthritis. However, the stable delivery of LSF remains a major challenge. Methotrexate (MTX) is currently the first line treatment for managing RA and is most effective in patients when used in combination with other anti-inflammatory or anti-rheumatic drugs. Here we developed phenylboronic acid-PAMAM dendrimer (PBA-G5D) nanoparticles conjugated MTX (MTX-PBA-G5D), and L-sulforaphane (LSF/PBA-G5D) loaded dendrimers. The MTX and LSF drug loading and release kinetics was analyzed using HPLC. The lipopolysaccharide (LPS) stimulated macrophages were treated with the formulations to study the inflammatory response in vitro. For in vivo studies, arthritis was induced in five-week-old female Wistar rats, and the MTX- and LSF/PBA-G5-D were injected via intra-articular injection for treatment and the arthritis reduction was scored by weight, knee diameter, and serum cytokine level measurement. The average size of the drug-nanoparticle conjugates ranged from 135 to 250 nm, with mostly cationic surface charges. The encapsulation efficiency of the drugs to the modified dendrimer was more than 60% with a slow release of drugs from the nanoparticles within 24 h at pH 7.4. Drugs in the nanoparticle formulation were biocompatible, with promising anti-inflammatory effects in vitro against LPS-activated murine macrophages. Further in vivo studies on arthritis induced female Wistar rats, revealed significant anti-arthritic effects based on the arthritic scoring from the knee diameter reading, and anti-inflammatory effects based on the serum cytokine levels. This study provides a promising strategy for utilizing PAMAM dendrimers as a nanocarrier for LSF delivery for RA therapy.

Improved in vitro biocompatibility and cytoplasmic localization of gold nanoparticles and graphene oxide nanosheets assessed using confocal microscopy

Nanomaterial-based delivery platforms have indeed revolutionized drug delivery systems in recent years. These platforms, which are based on various types of nanoparticles, offer several advantages over traditional drug delivery systems. Therefore, during this work, we synthesized gold nanoparticles (GNPs) and graphene oxide (GO) as representative nanomaterials and assessed their biocompatibility and cytoplasmic localization in vitro. Structural characterization of the prepared nanoparticles was performed by using different techniques. For instance, laser diffraction spectrometry using a Nano-ZS Zetasizer was used to determine the particles size, and Zeta potential. High-resolution transmission electron microscopy (HR-TEM) were utilized to evaluate Particle sizes and morphologies of the prepared nanoparticles. Additionally, the chemical structure of the prepared nanoparticles was assessed by X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR). The effects of the different concentrations of GNPs and GO nanosheets on cell viability and proliferation were evaluated by WST-1 cell proliferation assays. Ultimately, in vitro studies were performed by confocal microscopy to characterize the cellular uptake of the prepared nanoparticles. The net results of this study suggest that both nanomaterials showed a cytoplasmic entry without penetrating the nucleus. They may be useful for slow drug release as well as photothermal and photodynamic therapy using a low-powered laser or IR radiation.

M6P-modified solid lipid nanoparticles loaded with matrine for the treatment of fibrotic liver

Liver fibrosis is a key pathological process shared by the progression of various chronic liver diseases. Treatment of liver fibrosis can effectively block the occurrence and development of hepatic cirrhosis or even carcinoma. Currently, there is no effective drug delivery vehicle for curing liver fibrosis. In this study, we designed matrine (MT)-loaded mannose 6-phosphate (M6P) modified human serum albumin (HSA) conjugated solid lipid nanoparticles (SLN), named M6P-HSA-MT-SLN for treatment of hepatic fibrosis. We demonstrated that M6P-HSA-MT-SLN exhibited controlled and sustained release properties and good stability over 7 days. The drug release experiments showed that M6P-HSA-MT-SLN exhibited slow and controlled drug release characteristics. In addition, M6P-HSA-MT-SLN showed a significant targeted ability to fibrotic liver. Importantly, in vivo studies indicated that M6P-HSA-MT-SLN could significantly improve histopathological morphology and inhibit the fibrotic phenotype. In addition, in vivo experiments demonstrate that M6P-HSA-MT-SLN could reduce the expression of fibrosis markers and alleviate the damage of liver structure. Hence, the M6P-HSA-MT-SLN provide a promising strategy to deliver therapeutic agents to fibrotic liver to prevent liver fibrosis.

SBA‐15 Particles as Carriers for a Series of Platinum(IV) Complexes with Oxaliplatin Scaffolds Bearing Different Anti‐Inflammatory Drugs: Promising Strategy Against Breast Cancer

AbstractOxaliplatin is a third‐generation platinum(II)‐based drug mainly utilized to treat colon cancer, as part of a combinatory regime. Aiming to expand the knowledge on the effects of oxaliplatin and its derivatives on different tumor types, oxaliplatin‐based platinum(IV) platforms are designed and prepared to assess their antitumor capacity against various breast cancer cell lines. In the two axial positions of the platinum(IV) system, different inflammation reducing agents, non‐steroidal anti‐inflammatory drugs (fenoprofen, flurbiprofen, both as racemates) and phenolic acids (acetyl‐protected and unprotected ferulic acid, cinnamic acid) are incorporated as anionic ligands. The prepared platinum(IV) hybrids are loaded with great encapsulation efficiency into mesoporous SBA‐15 material to serve as drug delivery vehicle, and the obtained nanostructured material can ensure very slow drug release beneficial for prolonged circulation in vivo and passive targeting. Both, free and in SBA‐15 immobilized platinum(IV) complexes with oxaliplatin core, displayed potent antitumor activity in four breast cancer cell lines (MCF‐7, BT‐474, HCC1937 and MDA‐MB‐468), showing great prospect in overcoming oxaliplatin and cisplatin resistance. Mechanistic investigations in MDA‐MB‐468 cells of oxaliplatin and its fenoprofen derivative as the most active representative of the prepared complexes showed that the decreased cell viability resides in activation of apoptotic mechanisms.

Microneedle-Assisted Topical Delivery of Idebenone-Loaded Bioadhesive Nanoparticles Protect against UV-Induced Skin Damage.

Ultraviolet (UV) radiation can penetrate the basal layer of the skin and induce profound alterations in the underlying dermal tissues, including skin pigmentation, oxidative stress, photoaging, glycation, and skin cancer. Idebenone (IDB), an effective antioxidant that suppresses melanin biosynthesis and glycation, can protect the skin from UV-induced damage, accounting for its use in commercial anti-aging formulations. Ideally, IDB formulations should retain IDB inside the skin for a sufficient period, despite disturbances such as sweating or swimming. Herein, we present an IDB topical formulation based on Tris (tris(hydroxymethyl)-aminomethane)-modified bioadhesive nanoparticles (Tris-BNPs) and microneedle-assisted delivery. We found that Tris-BNPs loaded with IDB (IDB/Tris-BNPs) effectively reached the basal layer of the skin and were retained for at least 4 days with a slow and continuous drug release profile, unlike non-bioadhesive nanoparticles (NNPs) and bioadhesive nanoparticles (BNPs) of similar sizes (ranging from 120-142 nm) and zeta-potentials (above -20 mV), which experienced a significant reduction in concentration within 24 h. Notably, IDB/Tris-BNPs showed superior performance against UV-induced damage relative to IDB/NNPs and IDB/BNPs. This effect was demonstrated by lower levels of reactive oxygen species and advanced glycation end-products in skin tissues, as well as suppressed melanogenesis. Therefore, the proposed IDB delivery strategy provided long-term protective effects against UV-induced skin damage.

Magnetic Hydrogel Microrobots Delivery System for Deafness Prevention

AbstractHydrogel microrobots have blazed new avenues for local drug administration, while their values in inner ear drug delivery remain to be explored. Here, novel magnetic alpha‐lipoic acid (ALA)‐conjugated gelatin methacryloyl hydrogel microrobots are presented for inner ear drug delivery and deafness prevention. The magnetic hydrogel microrobots with features of slow drug release, targeted movement, and biosafety are generated from microfluidic devices. After intratympanic injection, the microrobots can be oriented in the middle ear cavity under a specific magnetic field. In addition, the ALA drug released from the magnetic hydrogel microrobots can remain in the inner ear for a long time. Based on these advantages, the practical value of the magnetic hydrogel microrobots in deafness prevention is demonstrated by pre‐injecting them in the middle ear of cisplatin‐deafened mice. These results indicate that the proposed smart magnetic hydrogel microrobots can effectively deliver drugs to the inner ear through the middle ear drug delivery route, thus opening a new chapter for middle ear deafness treatment.

Development and in functional study of a bi-specific sustained release drug-loaded nano-liposomes for hepatocellular carcinoma.

Lenvatinib (LEN) is a first-line therapy for patients with hepatocellular carcinoma (HCC), but has a larger adverse effect profile. In this study, we developed a liposome with drug-carrying function and magnetic resonance imaging (MRI) imaging function to investigate the targeted drug-carrying function and MRI tracing ability of liposome for HCC. Magnetic nano-liposomes (MNL) with dual targeting function of epithelial cell adhesion molecule (EpCAM) and vimentin and capable of encapsulating LEN drugs were prepared. The characterization performance, drug loading efficiency and cytotoxicity of EpCAM/vimentin-LEN-MNL were tested, and the dual-targeting slow release drug loading function and MRI tracing ability were investigated in cellular and animal models. EpCAM/vimentin-LEN-MNL has a mean particle size of 218.37 ± 5.13nm and a mean potential of 32.86 ± 4.62mV, and is spherical in shape and can be uniformly dispersed in solution. The encapsulation rate was 92.66 ± 0.73% and the drug loading rate was 9.35 ± 0.16%. It has low cytotoxicity, can effectively inhibit HCC cell proliferation and promote HCC cell apoptosis, and has specific targeting function and MRI tracing ability for HCC cells. In this study, an HCC-specific dual-targeted sustained-release drug delivery liposome with dual-targeted recognition and sensitive MRI tracer was successfully prepared, which provides an important scientific basis for maximizing the multiple effects of nano-carriers in tumor diagnosis and treatment.

Fabrication of Poly(ε-caprolactone)-embedded Lignin-Chitosan Nanocomposite Porous Scaffolds from Pickering Emulsions.

Poly(ε-caprolactone) (PCL)-incorporated lignin-chitosan biomass-based nanocomposite porous scaffolds have been effectively prepared by templating oil-in-water Pickering high internal phase emulsions (HIPEs). PCL is dissolved in oil and chitosan and lignin nanoparticles originate in water. The continuous phase of the emulsions is gelled by cross-linking of chitosan with genipin and then freeze-dried to obtain porous scaffolds. The resulting scaffolds display interconnected and tunable pore structures. An increase in PCL content increases the mechanical strength and greatly reduces the water absorption capacity of the scaffolds. Scaffolds loaded with the anti-bacterial drug enrofloxacin show a slow drug release profile, adjustable release rate, and favorable long-term anti-bacterial activity. Moreover, Pickering emulsion templates with suitable viscosity are used as 3D printing inks to construct porous scaffolds with personalized geometry. The results imply that the simplicity and versatility of the technique of combining freeze-drying with Pickering HIPE templates is a promising approach to fabricate hydrophobic biopolymer-incorporated biomass-based nanocomposite porous scaffolds for biomedical applications.

Multifunctional Extracellular Matrix Hydrogel with Self-Healing Properties and Promoting Angiogenesis as an Immunoregulation Platform for Diabetic Wound Healing

Treating chronic wounds is a global challenge. In diabetes mellitus cases, long-time and excess inflammatory responses at the injury site may delay the healing of intractable wounds. Macrophage polarization (M1/M2 types) can be closely associated with inflammatory factor generation during wound healing. Quercetin (QCT) is an efficient agent against oxidation and fibrosis that promotes wound healing. It can also inhibit inflammatory responses by regulating M1-to-M2 macrophage polarization. However, its limited solubility, low bioavailability, and hydrophobicity are the main issues restricting its applicability in wound healing. The small intestinal submucosa (SIS) has also been widely studied for treating acute/chronic wounds. It is also being extensively researched as a suitable carrier for tissue regeneration. As an extracellular matrix, SIS can support angiogenesis, cell migration, and proliferation, offering growth factors involved in tissue formation signaling and assisting wound healing. We developed a series of promising biosafe novel diabetic wound repair hydrogel wound dressings with several effects, including self-healing properties, water absorption, and immunomodulatory effects. A full-thickness wound diabetic rat model was constructed for in vivo assessment of QCT@SIS hydrogel, in which hydrogels achieved a markedly increased wound repair rate. Their effect was determined by the promotion of the wound healing process, the thickness of granulation tissue, vascularization, and macrophage polarization during wound healing. At the same time, we injected the hydrogel subcutaneously into healthy rats to perform histological analyses of sections of the heart, spleen, liver, kidney, and lung. We then tested the biochemical index levels in serum to determine the biological safety of the QCT@SIS hydrogel. In this study, the developed SIS showed convergence of biological, mechanical, and wound-healing capabilities. Here, we focused on constructing a self-healing, water-absorbable, immunomodulatory, and biocompatible hydrogel as a synergistic treatment paradigm for diabetic wounds by gelling the SIS and loading QCT for slow drug release.

Fabrication and Evaluation of Aceclofenac-loaded Sustained-Release Mucoadhesive Tablet Composed of Cassia fistula Seed Gum-Grafted-Poly (Sodium Acrylate)

Aim: This study was aimed to fabricate gastroretentive mucoadhesive sustained-release tablets of aceclofenac with Cassia fistula seed gum-grafted-poly(sodium acrylate) and evaluate them.&#x0D; Background: Aceclofenac has several gastric related side effects such as increase in acid secretion, gastritis, burning sensation, nausea, vomiting, etc. Sustained-release tablet may reduce these because of slow drug release. But long term use of conventional sustained-release tablets of NSAIDs showed to develop colorectal ulcer. Gastroretentive sustained-release devices may eliminate this problem.&#x0D; Objective: The objective was to synthesis Cassia fistula seed gum-grafted-poly(sodium acrylate) and apply it in the fabrication of novel mucoadhesive sustained-release tablet for aceclofenac delivery in stomach.&#x0D; Method: CFSG-grafted-poly(sodium acrylate) (CFSG-g-PSA) was synthesized by microwave-assisted free-radical initiation method using ceric ammonium nitrate (CAN) as free-radical initiator. The tablets were prepared with the graft-copolymer by wet granulation technique. Compatibility between drug and graft-copolymer was checked by FTIR, DSC and PXRD. Surface topography of the uncoated matrix tablets was studied by SEM. The tablets were evaluated for weight variation, content uniformity, dimension, disintegration test, mucoadhesive and drug-release. accelerated stability study was also done.&#x0D; Results: FTIR, DSC and PXRD studies substantiated the drug-polymer compatibility. The evaluation parameters were within prescribed limit. The study revealed excellent mucoadhesive property over 10 h and sustained-drug-release pattern following zero order kinetic. Similarity factor was found to be 83.4.&#x0D; Conclusion: The study demonstrates a simple approach of functionalization of biopolymer towards development of gastroretentive mucoadhesive sustained-release tablet formulation.

Nanosome-Mediated Delivery Of Hdac Inhibitors and Oxygen Molecules for the Transcriptional Reactivation of Latent Hiv-Infected Cd4+ T Cells.

The treatment of human immunodeficiency virus (HIV) infection is notoriously difficult due to the ability of this virus to remain latent in the host's CD4+ T cells. Histone deacetylases (HDACs) interfere with DNA transcription in HIV-infected hosts, resulting in viral latency. Therefore, HDAC inhibitors can be used to activate viral transcription in latently infected cells, after which the virus can be eliminated through a shock-and-kill strategy. Here, a drug delivery system is developed to effectively deliver HDAC inhibitors to latent HIV-infected cells. Given that the efficacy of HDAC inhibitors is reduced under hypoxic conditions, oxygen-containing nanosomes are used as drug carriers. Oxygen-containing nanosomes can improve the efficiency of chemotherapy by delivering essential oxygen to cells. Additionally, their phospholipid bilayer structure makes them uniquely well-suited for drug delivery. In this study, a novel drug delivery system is developed by taking advantage of the oxygen carriers in these oxygen nanosomes, incorporating a multi-drug strategy consisting of HDAC inhibitors and PKA activators, and introducing CXCR4 binding peptides to specifically target CD4+ T cells. Oxygen nanosomes with enhanced targeting capability through the introduction of the CXCR4 binding peptide mitigate drug toxicity and slow down drug release. The observed changes in the expression of p24, a capsid protein of HIV, indirectly confirm that the proposed drug delivery system can effectively induce transcriptional reactivation of HIV in latent HIV-infected cells.

L-Lysine-Modified pNIPAm-co-GMA Copolymer Hydrogel for pH- and Temperature-Responsive Drug Delivery and Fluorescence Imaging Applications.

The development of dual-stimuli-responsive hydrogels attracts much research interest owing to its unique stimuli-responsive characteristics. In this study, a poly-N-isopropyl acrylamide-co-glycidyl methacrylate-based copolymer was synthesized by incorporating N-isopropyl acrylamide (NIPAm) and a glycidyl methacrylate (GMA) monomer. The synthesized copolymer, pNIPAm-co-GMA was further modified with L-lysine (Lys) functional units and further conjugated with fluorescent isothiocyanate (FITC) to produce a fluorescent copolymer pNIPAAm-co-GMA-Lys hydrogel (HG). The in vitro drug loading and dual pH- and temperature-stimuli-responsive drug release behavior of the pNIPAAm-co-GMA-Lys HG was investigated at different pH (pH 7.4, 6.2, and 4.0) and temperature (25 °C, 37 °C, and 45 °C) conditions, respectively, using curcumin (Cur) as a model anticancer drug. The Cur drug-loaded pNIPAAm-co-GMA-Lys/Cur HG showed a relatively slow drug release behavior at a physiological pH (pH 7.4) and low temperature (25 °C) condition, whereas enhanced drug release was achieved at acidic pH (pH 6.2 and 4.0) and higher temperature (37 °C and 45 °C) conditions. Furthermore, the in vitro biocompatibility and intracellular fluorescence imaging were examined using the MDA-MB-231 cell line. Therefore, we demonstrate that the synthesized pNIPAAm-co-GMA-Lys HG system with temperature- and pH-stimuli-responsive features could be promising for various applications in biomedical fields, including drug delivery, gene delivery, tissue engineering, diagnosis, antibacterial/antifouling material, and implantable devices.