Sustained Drug Release Research Articles

PH-responsive mupirocin-loaded hybrid nanoparticles in hydrogel and film forming spray against resistant bacterial wound infections

The aim of this work was to fabricate smart Mupirocin loaded Lipid Polymeric Hybrid Nanoparticles (MUP-LPHNs) based hydrogel and Film forming spray (FFS) for targeted release of MUP in response to wound pH. The MUP-LPHNs were optimized through design expert v.12. The optimized MUP-LPHNs had a particle size of 270.7 ± 3.20 nm with zeta potential of 17.05 ± 1.20 mV and entrapment efficiency of 88.0 ± 0.35 %. MUP-LPHNs showed no major chemical interaction, spherical morphology and amorphous nature as confirmed by FTIR, SEM and XRD, respectively. MUP-LPHNs were loaded to MUP-LPHNs based hydrogel (MUP-LPHNs-HG) and MUP-LPHNs based film forming spray (MUP-LPHNs-FFS) with successful characterization. In vitro release data confirmed sustained and pH dependent release from both MUP-LPHNs-HG and MUP-LPHNs-FFS as higher release was observed at pH 7.4. MUP-LPHNs-HG and MUP-LPHNs-FFS showed high efficiency and long-term inhibition of Staphylococcus aureus (SA), Methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa (P. aeruginosa) with 4–6 fold increase in the antibacterial activity compared to MUP solution. MUP-LPHNs-HG and MUP-LPHNs-FFS exhibited both in vitro and in vivo wound pH contingent, sustained drug release. Moreover, the prepared nanocarriers systems flaunted significant therapeutic efficacy against MRSA infected wound model by significant reduction in bacterial load and wound area, increased hydroxy proline level and antioxidant enzymes and reduced proinflammatory cytokines. Similarly, immunohistochemistry, histopathological and trichrome assessment showed significant reduction in level of inflammatory markers, accelerated and enhanced re-epithelization, improved connective tissue remodeling and effectively promote collagen deposition with effective wound regeneration, respectively. It can be concluded that LPHNs could be a potential carrier system for enhancing the therapeutic efficacy of MUP against resistant bacterial wound infections.

3D-printed implants loaded with acriflavine for glioblastoma treatment

Drug delivery routes play an essential role in determining the efficacy and safety of medications. This study focused on the development and optimization of 3D-printed reservoir type implants as a combinational therapy drug delivery system for Glioblastoma Multiforme (GBM) post-surgery, possessing also antibacterial properties. In this study, we used a multimodal agent, Acriflavine (ACF) as an alternative drug to treat GBM. To date, ACF is used only as an antiseptic agent, although it has been shown to possess strong anticancer activities. ACF and a low molecular weight PCL were loaded into 3D-printed reservoir-type implants for sustained drug delivery. The study demonstrated that ACF implants exhibited sustained drug release kinetics, with faster release during the initial 30 days, followed by a gradual decrease over 90 days. This controlled release profile enhances the effectiveness of ACF delivery to tumour targets while minimizing side effects associated with systemic administration. In vitro experiments confirmed the inhibitory activity of ACF against GBM cells compared to non-tumour cells. The study also highlighted the bacteriostatic effects of ACF, making the implants potentially useful for post-surgery infection management, particularly against S. aureus, a common bacterial infection associated with brain surgery. The long-term drug-release capabilities of the implants make them attractive candidates for both tumour inhibition and antibacterial treatment. The study suggests that the developed ACF delivery systems have the potential for future clinical studies. Their ability to provide increased drug efficacy without systemic toxicity makes them promising candidates for cancer therapy and post-surgery infection management.

A Self-Skin Permeable Doxorubicin Loaded Nanogel Composite as a Transdermal Device for Breast Cancer Therapy.

Modern drug delivery research focuses on developing biodegradable nanopolymer systems. The present study proposed a polymer-based composite nanogel as a transdermal drug delivery system for the pH-responsive targeted and controlled delivery of anticancer drug doxorubicin (DOX). Nanogels have properties of both hydrogels and nanomaterials. The β-cyclodextrin-based nanogels can enhance the loading capacity of poorly soluble drugs and promote a sustained drug release. The β-cyclodextrin-grafted methacrylic acid conjugated hyaluronic acid composite nanogel was successfully synthesized. β-Cyclodextrin was first grafted onto methacrylic acid. The composite nanogel-based drug carrier was prepared by controlled radical polymerization (CRP) of β-cyclodextrin-grafted methacrylic acid with hyaluronic acid. The doxorubicin-loaded carrier was characterized by Fourier transform infrared (FTIR) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, ultraviolet-visible (UV-vis) spectroscopy, zeta potential analysis, dynamic light scattering (DLS), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). The drug loading and release efficiencies were carried out at different pH levels. The maximum drug loading and encapsulation efficiencies of the synthesized final nanogel composite material at pH 8.0 were 86.44 ± 2.12 and 96.07 ± 2.01%, respectively. The DOX-loaded final material showed a 90.0 ± 2.6% release percentage of DOX at pH 5.5, whereas at pH 7.4, the release percentage of DOX was observed to be only 35.0 ± 0.3%. In vitro swelling, degradation, hemocompatibility, drug release kinetics, cytotoxicity, apoptosis, cell colocalization, skin irritation, and skin permeation studies, along with in vivo pharmacokinetic studies, were performed to prove the efficacy of the synthesized nanogel composite as a transdermal carrier for doxorubicin.

Design and Evaluation of New Gel-Based Floating Matrix Tablets Utilizing the Sublimation Technique for Gastroretentive Drug Delivery.

A gel-based floating matrix tablet was formulated and evaluated using the sublimation technique to enhance gastroretentive drug delivery. Anhydrous theophylline was employed as the active pharmaceutical ingredient, combined with sublimation agents and hydroxypropyl methylcellulose as the gel-forming polymer. The resulting tablets exhibited high porosity, immediate floatation, and sustained buoyancy for over 8 h. Optimization of the floating behavior and drug release profiles was achieved by adjusting the viscosity of and hydroxypropyl methylcellulose and the concentration of sublimation agents, specifically ammonium carbonate and menthol. These agents were selected for their effectiveness in creating a porous structure, thus reducing tablet density and enhancing floatation. Higher HPMC viscosity resulted in increased floating force, slower drug release, and improved swelling properties due to a slower erosion rate. A critical assessment of the balance between tablet porosity, mechanical strength, and drug release kinetics indicates that ammonium carbonate provided superior tablet hardness and lower friability compared to menthol, favoring a controlled release mechanism. The release dynamics of theophylline were best described by the anomalous (non-Fickian) diffusion model, suggesting a combined effect of diffusion and erosion. This research advances the development of gastroretentive drug delivery systems, highlighting the potential of sublimation-based floating matrix tablets for sustained drug release.

A multifunctional polyacrylonitrile fibers/alginate-based hydrogel loaded with chamomile extract and silver sulfadiazine for full-thickness wound healing

Most conventional wound dressings do not meet the clinical requisites owing to their limited multifunctionality. Herein, a bilayer wound dressing containing both hydrogel and fibrous structures with multifunctional features was developed for effective skin rehabilitation. Sodium alginate (SA)/gelatin (Gel) hydrogel comprising Matricaria chamomilla L extract and silver sulfadiazine (AgSD) drug as antibacterial agents was cross-linked using genipin and CaCl2. Then, the surface of the hydrogel was covered by electrospun polyacrylonitrile (PAN) nanofibers to fabricate a bilayer dressing. FESEM images revealed formation of continuous, smooth, and bead-free PAN nanofibers with excellent compatibility between hydrogel and fibers. The bilayer wound dressing exhibited satisfactory mechanical virtues including elastic modulus (2.4 ± 0.2 MPa), tensile strength (6.2 ± 0.5 MPa) and elongation at break (21.8 ± 1 %) as well as suitable swelling ratio. Such bilayer dressing revealed biodegradability, cytocompatibility and effective antibacterial performance against gram positive and gram negative strains. Release kinetics of AgSD drug followed a Fickian diffusion mechanism, ensuring sustained drug release. In vivo studies demonstrated bilayer dressing could promote rate of wound closure, re-epithelialization and collagen deposition, facilitating the replacement of damaged skin with healthy tissue. Such engineered wound dressing has a high potency for inducing skin repair and could be used in skin tissue engineering.

Two-step emulsification for the fabrication of homogeneous PCL microspheres encapsulating geniposidic acid with antioxidant properties

The mortality rate of neurological disorders is increasing globally, and natural antioxidant geniposidic acid (GPA) holds great potential in the treatment of neuronal oxidative damage. Nevertheless, its inherent instability constrains its pragmatic utilization. Herein, we introduced a drug delivery system capable of protecting unstable natural active compounds from degradation. Among the various methods for preparing drug-loaded microspheres, the emulsification-solvent evaporation technique is one of the most commonly employed due to its efficiency and simplicity. Nevertheless, this method results in microspheres with heterogeneous particle sizes. To address this limitation, we developed a two-step emulsification method involving stirring and homogenization. Using the biocompatible, synthetic, biodegradable polymer polycaprolactone (PCL) as the drug delivery carrier, we prepared GPA-loaded PCL microspheres via the two-step emulsification method. The results demonstrated that the microspheres possessed uniform particle size (polydispersity index = 0.12), excellent drug loading capacity (∼4.86%), sustained drug release profiles (∼68.55% in 264 h), and biocompatibility (cell viability >85%). The in vitro tests showed that the microspheres exerted antioxidant effects by scavenging reactive oxygen species (ROS) induced by oxidative stress, thereby protecting neuronal cells from oxidative damage. This work presents a promising new approach for the treatment of neuronal oxidative damage.

Development of Mitoxantrone-Loaded Quercetin Nanoparticles for Breast Cancer Therapy with Potential for Synergism with Bioactive Natural Products

Nanoparticle (NP)-based drug delivery systems have caused a paradigm shift in cancer treatment by enabling drug targeting, sustaining drug release, and reducing systemic toxicity of chemotherapy. Here we developed a novel NP formulation for the anticancer drug mitoxantrone (MTZ) by loading it into an emerging nanomaterial derived from the plant polyphenol quercetin (QCT). QCT was partially oxidized to produce amphiphilic oxQCT which was co-assembled with poly(ethylene glycol) (PEG) and MTZ by nanoprecipitation to form MTZ NPs. The optimal NPs exhibited an average diameter of 128 nm, a polydispersity index of 0.22, and a drug loading efficiency of 76%. While only a small fraction of the loaded drug was released at physiologic pH, a significantly higher fraction was released at acidic pH. The anticancer activity of MTZ NPs was assessed in MCF-7 and MDA-MB-231 breast cancer cell lines, alone and in combination with the bioactive natural products curcumin (CUR) and thymoquinone (TQ). In cell viability assays, MTZ NPs were slightly less potent than free MTZ, most likely due to their sustained release properties, but their cytotoxicity was greatly enhanced in the presence of TQ (in MCF-7 cells) as well as CUR (in MDA-MB-231 cells). The results were corroborated by apoptosis assays such as mitochondrial membrane potential measurement, acridine orange/ethidium bromide staining, in addition to caspase activity assays. The assays revealed that the NPs’ proapoptotic effect was enhanced in the presence of CUR or TQ, depending on the cell line. Our work presents a promising nanocarrier platform for MTZ with the potential to enhance its bioactivity against breast cancer when combined with bioactive natural products.

Development of Dual-Targeted Mixed Micelles Loaded with Celastrol and Evaluation on Triple-Negative Breast Cancer Therapy.

Considering that the precise delivery of Celastrol (Cst) into mitochondria to induce mitochondrial dysfunction may be a potential approach to improve the therapeutic outcomes of Cst on TNBC, a novel tumor mitochondria dual-targeted mixed-micelle nano-system was fabricated via self-synthesized triphenylphosphonium-modified cholesterol (TPP-Chol) and hyaluronic acid (HA)-modified cholesterol (HA-Chol). The Cst-loaded mixed micelles (Cst@HA/TPP-M) exhibited the characteristics of a small particle size, negative surface potential, high drug loading of up to 22.8%, and sustained drug release behavior. Compared to Cst-loaded micelles assembled only by TPP-Chol (Cst@TPP-M), Cst@HA/TPP-M decreased the hemolysis rate and upgraded the in vivo stability and safety. In addition, a series of cell experiments using the triple-negative breast cancer cell line MDA-MB-231 as a cell model proved that Cst@HA/TPP-M effectively increased the cellular uptake of the drug through CD44-receptors-mediated endocytosis, and the uptake amount was three times that of the free Cst group. The confocal results demonstrated successful endo-lysosomal escape and effective mitochondrial transport triggered by the charge converse of Cst@HA/TPP-M after HA degradation in endo-lysosomes. Compared to the free Cst group, Cst@HA/TPP-M significantly elevated the ROS levels, reduced the mitochondrial membrane potential, and promoted tumor cell apoptosis, showing a better induction effect on mitochondrial dysfunction. In vivo imaging and antitumor experiments based on MDA-MB-231-tumor-bearing nude mice showed that Cst@HA/TPP-M facilitated drug enrichment at the tumor site, attenuated drug systemic distribution, and polished up the antitumor efficacy of Cst compared with free Cst. In general, as a target drug delivery system, mixed micelles co-constructed by TPP-Chol and HA-Chol might provide a promising strategy to ameliorate the therapeutic outcomes of Cst on TNBC.

Exploring Protein-Based Carriers in Drug Delivery: A Review.

Drug delivery systems (DDSs) represent an emerging focus for many researchers and they are becoming progressively crucial in the development of new treatments. Great attention is given to all the challenges that a drug has to overcome during its journey across barriers and tissues and all the pharmacokinetics modulations that are needed in order to reach the targeting sites. The goal of these pathways is the delivery of drugs in a controlled way, optimizing their bioavailability and minimizing side effects. Recent innovations in DDSs include various nanotechnology-based approaches, such as nanoparticles, nanofibers and micelles, which provide effective targeted delivery and sustained release of therapeutics. In this context, protein-based drug delivery systems are gaining significant attention in the pharmaceutical field due to their potential to revolutionize targeted and efficient drug delivery. As natural biomolecules, proteins offer distinct advantages, including safety, biocompatibility and biodegradability, making them a fascinating alternative to synthetic polymers. Moreover, protein-based carriers, including those derived from gelatin, albumin, collagen, gliadin and silk proteins, demonstrate exceptional stability under physiological conditions, and they allow for controlled and sustained drug release, enhancing therapeutic efficacy. This review provides a comprehensive overview of the current trends, challenges, and future perspectives in protein-based drug delivery, focusing on the types of proteins adopted and the techniques that are being developed to enhance their functionality in terms of drug affinity and targeting capabilities, underscoring their potential to significantly impact modern therapeutics.

Bacteria-responsive drug release platform for the local treatment of bacterial vaginosis

Bacterial vaginosis (BV) is a common vaginal infection affecting millions of women. Vaginal anaerobic dysbiosis occurs whenLactobacillusspp., the dominant flora in healthy vagina is replaced by certain overgrown anaerobes, resulting in unpleasant symptoms such as vaginal discharge and odor. With a high recurrence rate, BV also severely impacts the overall quality of life of childbearing women by inducing preterm delivery and increasing the risks of pelvic inflammatory disease and sexually transmitted infections. Among various BV-associated bacteria,Gardnerella vaginalis(G. vaginalis) has been identified as a primary pathogen since it has been isolated from almost all women carrying BV and exhibits higher virulence potential over other bacteria. When dealing with BV relapse, intravaginal drug delivery systems are superior to conventional oral antibiotic therapies in improving therapeutic efficacy owing to more effective drug dose, reduced drug resistance and minimized side effects such as stomach irritation. Traditional intravaginal drug administration generally involves solids, semi-solids and delivery devices inserted into the vaginal lumen to achieve sustained drug release. However, they are mostly designed for continuous drug release and are not preventative therapies, resulting in severe side effects caused by excess dosing. Stimuli-responsive systems that can release drug only when needed ('on-demand') can help diminish these negative side effects. Hence, we developed a bacteria-responsive liposomal platform for the prevention and treatment of BV. This platform demonstrated sustained drug release in the presence of vaginolysin, a toxin secreted specifically byG. vaginalis. We prepared four liposome formulations and evaluated their responsiveness toG. vaginalis. The results demonstrated that the liposome formulations could achieve cumulative drug release ranging from 46.7% to 51.8% over a 3-5 d period in response toG. vaginalisand hardly any drug release in the presence ofLactobacillus crispatus(L. crispatus), indicating the high specificity of the system. Overall, the bacteria-responsive drug release platform has great potential, since it will be the first time to realize sustained drug release stimulated by a specific pathogen for BV prevention and treatment. This on-demand therapy can potentially provide relief to the millions of women affected by BV.

The assessment of pharmacokinetics and neuroprotective effect of berberine hydrochloride-embedded albumin nanoparticles via various administration routes: comparative in-vivo studies in rats.

The current study aimed to evaluate the pharmacokinetics and neuroprotective effect of well-characterised berberine-bovine serum albumin (BBR-BSA) nanoparticles. BBR-BSA nanoparticles were generated by desolvation method. Entrapment efficiency, loading capacity, particle size, polydispersity index, surface morphology, thermal stability, and in-vitro release were estimated. In-vitro pharmacokinetic and tissue distribution were conducted. Their neuroprotection was evaluated against lipopolysaccharides-induced neurodegeneration. BBR-BSA nanoparticles showed satisfactory particle size (202.60 ± 1.20 nm) and entrapment efficiency (57.00 ± 1.56%). Results confirmed the formation of spheroid-thermal stable nanoparticles with a sustained drug release over 48 h. Sublingual and intranasal routes had higher pharmacokinetic plasma profiles than other routes, with Cmax values at 0.75 h (444 ± 77.79 and 259 ± 42.41 ng/mL, respectively). BBR and its metabolite distribution in the liver and kidney were higher than in plasma. Intranasal and sublingual treatment improves antioxidants, proinflammatory, amyloidogenic biomarkers, and brain architecture, protecting the brain. In conclusion, neuroinflammation and neurodegeneration may be prevented by intranasal and sublingual BBR-BSA nanoparticles.

Prolonged, staged, and self-regulated methotrexate release coupled with ROS scavenging in an injectable hydrogel for rheumatoid arthritis therapy

Rheumatoid arthritis (RA) remains a formidable healthcare challenge due to its chronic nature and potential for irreversible joint damage. Methotrexate (MTX) is a cornerstone treatment for RA but carries significant risks of adverse effects with repeated administration, necessitating the exploration of alternative delivery methods. Injectable hydrogels loaded with MTX for intra-articular injection present a promising solution, allowing sustained drug release directly into affected joints. However, current hydrogel systems often lack extended therapeutic periods and the ability to self-regulate drug release according to disease state. Furthermore, RA is associated with excessive production of reactive oxygen species (ROS), which exacerbates inflammation and joint damage. Herein, we developed an advanced injectable hydrogel (MPDANPs/MTX HA-PEG gel) based on “bio-orthogonal chemistry”, combining hyaluronic acid and polyethylene glycol (PEG) matrices co-loaded with mesoporous polydopamine nanoparticles (MPDANPs) and MTX. MPDANPs/MTX HA-PEG gel achieved prolonged, staged, and self-regulated MTX release, coupled with ROS scavenging capabilities for enhanced therapeutic efficacy. Due to its optimized MTX release behavior and significant ROS scavenging function, MPDANPs/MTX HA-PEG gel exhibited potent anti-inflammatory effects in collagen-induced arthritis (CIA) rats following a single intra-articular injection. Our findings highlight the potential of MPDANPs/MTX HA-PEG gel as a highly effective treatment strategy for RA, offering a promising avenue for improving patient outcomes.

Continuously producible aztreonam-loaded inhalable lipid nanoparticles for cystic fibrosis-associated Pseudomonas aeruginosa infections – Development and in-vitro characterization

Cystic fibrosis (CF) is a genetic disorder affecting nearly 105,000 patients worldwide and is characterized by poor respiratory function due to accumulation of thick mucus in the lungs, which not just acts as a physical barrier, but also provides a breeding ground for bacterial infections. These infections can be controlled with the help of antibiotics which can be delivered directly into the lungs for amplifying the local anti-bacterial effect. More than 50 % of CF patients are associated with Pseudomonas aeruginosa infection in their lungs which requires antibiotics such as Aztreonam (AZT). In this study, we prepared inhalable AZT-loaded lipid nanoparticles using Hot-melt extrusion (HME) coupled with probe sonication to target Pseudomonas aeruginosa infection in the lungs. The optimized nanoparticles were tested for physicochemical properties, stability profile, in-vitro aerosolization, and antimicrobial activity against Pseudomonas aeruginosa. The optimized nanoparticles with a PEI concentration of 0.1 % demonstrated a uniform particle size of <50 nm, a spherical shape observed under a transmission electron microscope, and >70 % drug entrapment. Incorporating cationic polymer, PEI, resulted in sustained drug release from the lipid nanoparticles. The in-vitro aerosolization studies exhibited a mass median aerodynamic diameter (MMAD) of <4.3 μm, suggesting deposition of the nanoparticles in the respirable airway. The antimicrobial activity against Pseudomonas aeruginosa showed the minimum inhibitory concentration of the formulation is 2-fold lower than plain AZT. Stability profile showed the formulations are stable after exposure to accelerated conditions. In conclusion, hot-melt extrusion in combination with probe sonication can be used as a potential method for the continuous production of AZT-loaded lipid nanoparticles with enhanced anti-bacterial activity.

An in situ depot for the sustained release of a TLR7/8 agonist in combination with a TGFβ inhibitor promotes anti-tumor immune responses

Cancer curing immune responses against heterogeneous solid cancers require that a coordinated immune activation is initiated in the antigen avid but immunosuppressive tumor microenvironment (TME). The plastic TME, and the poor systemic tolerability of immune activating drugs are, however, fundamental barriers to generating curative anticancer immune responses. Here, we introduce the CarboCell technology to overcome these barriers by forming an intratumoral sustained drug release depot that provides high payloads of immune stimulatory drugs selectively within the TME. The CarboCell thereby induces a hot spot for immune cell training and polarization and further drives and maintains the tumor-draining lymph nodes in an anticancer and immune activated state. Mechanistically, this transforms cancerous tissues, consequently generating systemic anticancer immunoreactivity. CarboCell can be injected through standard thin-needle technologies and has inherent imaging contrast which secure accurate intratumoral positioning. In particular, here we report the therapeutic performance for a dual-drug CarboCell providing sustained release of a Toll-like receptor 7/8 agonist and a transforming growth factor-β inhibitor in preclinical tumor models in female mice.

Fiber Optics Analysis of Floating Hollow Microspheres for a Poorly Water-Soluble Drug

This study investigates the development and evaluation of floating hollow microspheres for the delivery of omeprazole, a poorly water-soluble drug. The research aims to enhance omeprazole's bioavailability by addressing its low solubility and susceptibility to degradation in an acidic gastric environment. Hollow ethyl cellulose microspheres encapsulating omeprazole were prepared using the solvent evaporation technique. The microspheres displayed 91.3% buoyancy and 82.41% drug entrapment efficiency, with sustained drug release in simulated gastric fluid over 12 hours. Characterization techniques such as X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM) were used. XRD analysis indicated that the encapsulated drug was in an amorphous state, improving dissolution rates and bioavailability. FTIR confirmed successful drug encapsulation, and SEM revealed the morphology and porous structure of the microspheres. The results highlighting the potential of floating hollow microspheres to enhance the oral bioavailability of poorly water-soluble drugs. Recommendations include refining the formulation process and exploring microfluidic technology for generating uniform microspheres with high drug loading. The study provides valuable insights for the development of advanced drug delivery systems.

Hybrid zinc oxide nanocoating on titanium implants: Controlled drug release for enhanced antibacterial and osteogenic performance in infectious conditions

Implant-associated bacterial infections are a primary cause of complications in orthopedic implants, and localized drug delivery represents an effective mitigation strategy. Drawing inspiration from the morphology of desiccated soil, our group has developed an advanced drug-delivery system augmented onto titanium (Ti) plates. This system integrates zinc oxide (ZnO) nanorod arrays with a vancomycin drug layer along with a protective Poly(lactic-co-glycolic acid) (PLGA) coating. The binding between the ZnO nanorods and the drug results in attached drug blocks, isolated by desiccation-like cracks, which are then encapsulated by PLGA to enable sustained drug release. Additionally, the release of zinc ions and the generation of reactive oxygen species (ROS) from the ZnO nanorods enhance the antibacterial efficacy. The antibacterial properties of ZnO nanorod-drug-PLGA system have been validated through both in vitro and in vivo studies. Comprehensive investigations were conducted on the impact of bacterial infections on bone defect regeneration and the role of this drug-delivery system in the healing process. Furthermore, the local immune response was analyzed and the immunomodulatory function of the system was demonstrated. Overall, the findings underscore the superior performance of the ZnO nanorod-drug-PLGA system as an efficient and safe approach to combat implant-associated bacterial infections. Statement of significanceImplant-associated bacterial infections pose a significant clinical challenge, particularly in orthopedic procedures. To address this, we developed an innovative ZnO nanorod-drug-PLGA system for local antibiotic delivery on conventional titanium implants. This system is biodegradable and features a unique desiccation-like structure that enables sustained drug release, along with the active substances released from the ZnO nanorods. In a rat calvarial defect model challenged with S. aureus, our system demonstrated remarkable antibacterial efficacy, significantly enhanced bone defect regeneration, and exhibited local immunomodulatory effects that support both infection control and osteogenesis. These breakthrough findings highlight the substantial clinical potential of this novel drug delivery system and introduce a transformative coating strategy to enhance the functionality of traditional metallic biomaterials.

Curcumin-loaded gold nanoparticles with enhanced antibacterial efficacy and wound healing properties in diabetic rats

Diabetic wounds pose a significant global health challenge. Although curcumin exhibits promising wound healing and antibacterial properties, its clinical potential is limited by low aqueous solubility, and poor tissue penetration. This study aimed to address these challenges and enhance the wound healing efficacy of curcumin by loading it onto gold nanoparticles (AuNPs). The properties of the AuNPs, including particle size, polydispersity index (PDI), zeta potential, percent drug entrapment efficiency (%EE) and UV–Vis spectra were significantly influenced by the curcumin/gold chloride molar ratio used in the synthesis of AuNPs. The optimal formulation (F2) exhibited the smallest particle size (41.77 ± 6.8 nm), reasonable PDI (0.59 ± 0.17), high %EE (94.43 ± 0.25 %), a moderate zeta potential (−8.44 ± 1.69 mV), and a well-defined surface Plasmon resonance peak at 526 nm. Formulation F2 was incorporated into Pluronic® F127 gel to facilitate its application to the skin. Both curcumin AuNPs solution and gel showed sustained drug release and higher skin permeation parameters compared with the free drug solution. AuNPs significantly enhanced curcumin’s antibacterial efficacy by lowering the minimum inhibitory concentrations and enhancing antibacterial biofilm activity against various Gram-positive and Gram-negative bacterial strains. In a diabetic wound rat model, AuNPs-loaded curcumin exhibited superior wound healing attributes compared to the free drug. Specifically, it demonstrated improved wound healing percentage, reduced wound oxidative stress, increased wound collagen deposition, heightened anti-inflammatory effects, and enhanced angiogenesis. These findings underscore the potential of AuNPs as efficacious delivery systems of curcumin for improved wound healing applications.

Reverse Gradient Distributions of Drug and Polymer Molecules within Electrospun Core-Shell Nanofibers for Sustained Release.

Core-shell nanostructures are powerful platforms for the development of novel nanoscale drug delivery systems with sustained drug release profiles. Coaxial electrospinning is facile and convenient for creating medicated core-shell nanostructures with elaborate designs with which the sustained-release behaviors of drug molecules can be intentionally adjusted. With resveratrol (RES) as a model for a poorly water-soluble drug and cellulose acetate (CA) and PVP as polymeric carriers, a brand-new electrospun core-shell nanostructure was fabricated in this study. The guest RES and the host CA molecules were designed to have a reverse gradient distribution within the core-shell nanostructures. Scanning electron microscope and transmission electron microscope evaluations verified that these nanofibers had linear morphologies, without beads or spindles, and an obvious core-shell double-chamber structure. The X-ray diffraction patterns and Fourier transform infrared spectroscopic results indicated that the involved components were highly compatible and presented in an amorphous molecular distribution state. In vitro dissolution tests verified that the new core-shell structures were able to prevent the initial burst release, extend the continuous-release time period, and reduce the negative tailing-off release effect, thus ensuring a better sustained-release profile than the traditional blended drug-loaded nanofibers. The mechanism underlying the influence of the new core-shell structure with an RES/CA reverse gradient distribution on the behaviors of RES release is proposed. Based on this proof-of-concept demonstration, a series of advanced functional nanomaterials can be similarly developed based on the gradient distributions of functional molecules within electrospun multi-chamber nanostructures.

Scope and Application of Hot Melt Extrusion in the Development of Controlled and Sustained Release Drug Delivery Systems.

Controlled-release drug delivery systems (CRDDS) are more beneficial than conventional immediate release (IRDDS) for reduced intake, prolonged duration of action, lesser adverse effects, higher bioavailability, etc. The preparation of CRDDS is more complex than IRDDS. The hot melt extrusion (HME) technique is used for developing amorphous solid dispersion of poorly water soluble drugs to improve their dissolution rate and oral bioavailability. HME can be employed to develop CRDDS. Sustained release delivery systems (SRDDS), usually given orally, can also be developed using HME. This technique has the advantages of using no organic solvent, converting crystalline drugs to amorphous, improving bioavailability, etc. However, the heat sensitivity of drugs, miscibility between drug-polymer, and the availability of a few polymers are some of the challenges HME faces in developing CRDDS and SRDDS. The selection of a suitable polymer and the optimization of the process with the help of the QbD principle are two important aspects of the successful application of HME. In this review, strategies to prepare SRDDS and CRDDS using HME are discussed with its applications in research.

Synthesis and in vitro study of biodegradable and thermoresponsive polymer based on polysuccinimide for drug delivery

Hydrogels, defined as polymer networks with a high water content and insoluble in water, have emerged as pivotal materials in biomedical research due to their resemblance to the natural extracellular matrix. The aim of this study is to develop an injectable, thermoresponsive, and biodegradable hydrogel. The hydrogel (PSI-t) was derived from poly (aspartic acid) (PSI) by grafting hydrophobic dodecylamine (DA) and hydrophilic ethanolamine (EA) groups onto its backbone. PSI-t was found to exhibit a unique sol state at room temperature, which facilitates facile injection, and undergoes rapid gelation at physiological temperatures, highlighting its potential as an injectable thermosensitive hydrogel for targeted drug delivery. In vitro tests confirmed the biocompatibility of the thermosensitive hydrogel, and sustained drug release studies using the model drug, acetaminophen (AP), underscored the efficacy of the hydrogel as a controlled release vehicle. Furthermore, the hydrogel was found to be easily eliminated through bio-hydrolysis, thus enabling prolonged drug effects while mitigating any potential toxicity. These findings suggest that PSI-t is a promising candidate for an innovative and injectable drug delivery system in biomedical applications.