Drug Release Performance Research Articles

An anti-infection and biodegradable TFRD-loaded porous scaffold promotes bone regeneration in segmental bone defects -experimental studies.

Addressing segmental bone defects remains a complex task in orthopedics, and recent advancements have led to the development of novel drugs to enhance the bone regeneration. However, long-term oral administration can lead to malnutrition and poor patient compliance. Scaffolds loaded with medication are extensively employed to facilitate the restoration of bone defects. Inspired by the local use of total flavonoids of Rhizoma Drynariae (TFRD) in the treatment of fracture, a novel 3D-printed HA/CMCS/PDA/TFRD scaffold with anti-infection, biodegradable and induced angiogenesis was designed, and to explore its preclinical value in segmental bone defect of tibia. The scaffold exhibited good degradation and drug release performance. In vitro, the scaffold extract promoted osteogenesis by enhancing bone-related gene/protein expression and mineral deposition in BMSCs. It also stimulated endothelial cell migration and promoted angiogenesis through the upregulation of specific genes and proteins associated with cell migration and tube formation. This may be attributed to the activation of the PI3k/AKT/HIF-1α pathway, facilitating the processes of osteogenesis and angiogenesis. Furthermore, the HA/CMCS/PDA/TFRD scaffold was demonstrated to alleviate infection, enhance angiogenesis, promote bone regeneration, and increase the maximum failure force of new formed bone in a rat model of segmental bone defects. Porous scaffolds loaded with TFRD can reduce infection, be biodegradable, and induce angiogenesis, presenting a novel approach for addressing tibial segmental bone defects.

Encapsulation and release of calcein from herceptin-conjugated eLiposomes

Achieving an optimal therapeutic level is crucial in effectively eradicating cancer cells during treatment. However, conventional chemotherapy-associated systemic administration of anticancer agents leads to many side effects. To achieve the desired control over the target site, active targeting of HER2-positive breast cancer cells can be achieved by conjugating liposomal vesicles with Human Epidermal growth factor Receptor 2 (HER2) and inducing release of the encapsulated drug using ultrasound. To further enhance the delivery efficiency, nanoemulsion droplets exhibiting responsiveness to low-frequency ultrasound are encapsulated within these lipid vesicles. In this study, we prepared four different liposomal formulations, namely pegylated liposomes, emulsion liposomes (eLiposomes), HER-conjugated liposomes, and HER-conjugated eLiposomes, each loaded with calcein and subjected to a thorough characterization process. Their sizes, phospholipid concentration, and amount of antibody conjugation were compared and analyzed. Cryogenic transmission electron microscopy was used to confirm the encapsulation of nanoemulsion droplets within the liposomes. The drug-releasing performance of Herceptin-conjugated eLiposomes was found to surpass that of other liposomal formulations with a notably higher calcein release and established it as a highly effective nanocarrier. The study showcases the efficacy of calcein-loaded and Herceptin-conjugated eLiposomes, which demonstrate rapid and efficient drug release among other liposomal formulations when subjected to ultrasound. This discovery paves the way for a more targeted, efficient, and humane approach to cancer therapy.

Structural Modulation of Chitosan/Polyacrylic Acid‐based Hydrogels for Optimized Controlled Drug Release Performance

AbstractA pH‐sensitive semi‐interpenetrating network hydrogel was synthesised by free radical polymerization using a one‐pot method using chitosan (CS) and alanine (AA) as the raw materials, and then the hydrogel was immersed in a solution of the model drug aspirin (Asa) for loading, and subsequently used for drug sustained‐release testing. The effects of the ratio of CS and AA on the internal structure of hydrogels were investigated, and the mechanism of CS/PAA semi‐interpenetrating network hydrogels upon drug slow release was explored. The results showed that increasing the composite ratio of PAA resulted in a subsequent increase in the drug loading capacity of CS/PAA hydrogels and the cumulative release of drugs. When the concentration of the drug‐loading solution was 200 mg/L, the drug loading and encapsulation efficiency of CS/PAA‐1 were 16.23±0.57 (%) and 72.16±3.84 (%), respectively (p < 0.05). The hydrogels showed significant pH‐responsive release properties and pH cycling reversibility, with 25.69±1.27 (%) and 77.21±2.68 (%) cumulative drug release over 24 h in the release media of pH 1.2 (simulating gastric fluid) and 7.4 (simulating intestinal fluid), respectively (p < 0.05), and the pH‐responsive reversible release of Asa was maintained in alternating cycles in the release media with pH 1.2 and 7.4.

Ivermectin-Loaded Mesoporous Silica and Polymeric Nanocapsules: Impact on Drug Loading, In Vitro Solubility Enhancement, and Release Performance.

Ivermectin (IVM), a widely used drug for parasitic infections, faces formulation and application challenges due to its poor water solubility and limited bioavailability. Pondering the impact of IVM's high partition coefficient value (log P) on its drug release performance, it is relevant to explore whether IVM nanoencapsulation in organic or inorganic nanoparticles would afford comparable enhanced aqueous solubility. To date, the use of inorganic nanoparticles remains an unexplored approach for delivering IVM. Therefore, here we loaded IVM in mesoporous silica particles (IVM-MCM), as inorganic nanomaterial, and in well-known poly(ε-caprolactone) nanocapsules (IVM-NC). IVM-MCM had a well-organized hexagonal mesoporous structure, reduced surface area, and high drug loading of 10% w/w. IVM-NC had a nanometric mean size (196 nm), high encapsulation efficiency (100%), physicochemical stability as an aqueous dispersion, and drug loading of 0.1% w/w. Despite differing characteristics, both nanoencapsulated forms enhance IVM's aqueous intrinsic solubility compared to a crystalline IVM: after 72 h, IVM-MCM and IVM-NC achieve 72% and 78% releases through a dialysis bag, whereas crystalline IVM dispersion achieves only 40% drug diffusion. These results show distinct controlled release profiles, where IVM-NC provides a deeper sustained controlled release over the whole experiment compared to the inorganic nanomaterial (IVM-MCM). Discussing differences, including drug loading and release kinetics, is crucial for optimizing IVM's therapeutic performance. The study design, combined with administration route plans and safety considerations for humans and animals, may expedite the rational optimization of IVM nanoformulations for swift clinical translation.

Biomimetic short fiber reinforced 3-dimensional scaffold for bone tissue regeneration

Bone defects caused by diseases and trauma are considered serious clinical challenges. Autologous and allogeneic transplantations are the most widely used methods to mitigate bone defects. However, transplantation poses risks such as secondary trauma, immune rejection, and disease transmission to patients. Preparing a biologically active bone tissue engineering scaffold as a bone substitute can overcome this problem. In the current study, a PLGA/gelatin (Gel) short fiber-reinforced composite three-dimensional (3D) scaffold was fabricated by electrospinning for bone tissue defect repair. A hybrid scaffold adding inorganic materials hydrotalcite (CaAl-LDH) and osteogenic factors deferoxamine (DFO) based on PLGA and Gel composite filaments was prepared. The structure, swelling, drug release, and compressive resilience performance of the 3D scaffolds in a wet state were characterized and the osteogenic effect of the crosslinked scaffold (C-DLPG) was also investigated. The scaffold has shown the optimum physicochemical attributes which still has 380 kPa stress after a 60% compression cycle and sustainedly released the drug for about twenty days. Moreover, a promising In vivo osteogenic performance was noted with better tissue organization. At 8 weeks after implantation, the C-DLPG scaffold could fill the bone defect site, and the new bone area reached 19 mm2. The 3D microfiber scaffold, in this study, is expected to be a promising candidate for the treatment of bone defects in the future.

Polyethylene glycol-stabilized cationic liposome encapsulating glucosamine sulfate: A promising nanoformulation for osteoarthritis therapy

Osteoarthritis (OA) is a common orthopedic chronic disease, and the use of nanomaterials as carriers is an effective way to realize slow and controlled release therapy for OA drugs. In this study, we synthesized a polyethylene glycol-stabilized bilayer-decorated cationic liposome (CLis) as a drug delivery system for delivering glucosamine sulfate (GS) drug to achieve the treatment of OA in rats. The CLis encapsulated with GS drug (GS-CLis) was prepared by a reverse evaporation method, and its physical properties, encapsulation rate, and drug release performance were evaluated. The biological properties of GS-CLis were evaluated in vitro. The therapeutic effect of GS-CLis on osteoarthritis was evaluated in vivo, and the in vivo biosafety of the drug was assessed by hematology, blood biochemistry, and hematoxylin-eosin staining. GS-CLis had a particle size of (236.28 ± 4.76) nm, a potential of (27.35 ± 4.86) mv, and a spherical shape. The encapsulation rate was (96.18 ± 5.77)% and the drug-loading capacity was (9.61 ± 0.28)%, which provided a good slow drug release. GS-CLis has low cytotoxicity, low hemolysis rate, and good biocompatibility. GS-CLis can more effectively alleviate joint surface damage and inhibit the expression of inflammatory factors, and has no significant effect on the body weight of rats, with good biological safety. In this study, we successfully synthesized novel GS-CLis for the treatment of OA, which improved the retention time and therapeutic effect of GS in OA and provided a research basis for its development as an OA nanoformulation.

Enhancing Bone Cement Efficacy with Hydrogel Beads Synthesized by Droplet Microfluidics

Effective filling materials, typically bone cements, are essential for providing mechanical support during bone fracture treatment. A current challenge with bone cement lies in achieving continuous drug release and forming porous structures that facilitate cell migration and enhance osteoconductivity. We report a droplet microfluidics-based method for synthesizing uniform-sized gelatin hydrogel beads. A high hydrogel concentration and increased crosslinking levels were found to enhance drug loading as well as release performance. Consequently, the droplet microfluidic device was optimized in its design and fabrication to enable the stable generation of uniform-sized droplets from high-viscosity gelatin solutions. The size of the generated beads can be selectively controlled from 50 to 300 μm, featuring a high antibiotic loading capacity of up to 43% dry weight. They achieve continuous drug release lasting more than 300 h, ensuring sustained microbial inhibition with minimal cytotoxicity. Furthermore, the hydrogel beads are well suited for integration with calcium phosphate cement, maintaining structural integrity to form porous matrices and improve continuous drug release performance. The uniform size distribution of the beads, achieved through droplet microfluidic synthesis, ensures predictable drug release dynamics and a measurable impact on the mechanical properties of bone cements, positioning this technology as a promising enhancement to bone cement materials.

Manganese Dioxide Nanoplatform with a Hollow Rhombic Dodecahedron Morphology for Drug Delivery.

Manganese dioxide (MnO2) is considered as a promising drug carrier material suitable for the tumor microenvironment while lacking conducive structures for drug loading. Herein, we construct a MnO2 nanoplatform with a hollow rhombic dodecahedral morphology for drug delivery. In this work, we obtained zeolitic imidazolate framework nanoparticles (ZIF-90 NPs) via a coordination reaction. Furthermore, the drug-loading nanoparticles (ZIF-90/DOX NPs) were obtained by Schiff's base reaction and then selected as a sacrificial template to obtain the hollow nanoplatforms (ZIF-90@MnO2 NPs). Moreover, the photothermal effect and multiresponsive drug release behaviors were revealed by loading the photothermal agent IR-820 and the anticancer drug doxorubicin hydrochloride (DOX). Our study demonstrates that the ZIF-90@MnO2 NPs loaded with photosensitizers exhibited excellent photothermal conversion performance. Benefiting from the hollow structure and redox activity, remarkable drug loading and release performances of ZIF-90@MnO2 NPs were achieved. It is shown that ZIF-90@MnO2 NPs achieved a satisfactory drug-loading efficiency (up to ca. 69.7%) for DOX. More promisingly, the ZIF-90@MnO2 NPs exhibited significant glutathione (GSH)/pH-responsive drug release and degradation performances. Overall, this work highlights the potential of controlled drug release of nanocarriers and offers unique insights into the design of nanocarriers with hollow structures.

Synthesis of (10-hydroxycamptothecin intercalated layered zinc hydroxide nitrate)@liposome nanocomposites for improving drug-release performance

A hierarchical nanocomposite of 10-hydroxycamptothecin (HCPT), a nonionic and lipophilic anticancer agent, intercalated layered zinc hydroxide nitrate (LZH) encapsulated in liposomes was fabricated. HCPT molecules were incorporated into sodium cholate (Ch) micelles, and the resulting negatively charged HCPT-loaded Ch micelles were then introduced into the LZH galleries to form an HCPT/Ch intercalated LZH (designated HCPT-Ch-LZH) host-guest nanohybrid. The nanohybrid particles were then coated with liposomes (LSs), resulting in the formation of a core-shell nanocomposite denoted as (HCPT-Ch-LZH)@LS. Using XRD, FT-IR, SEM, TEM, DLS, and elemental analyses, the obtained samples were characterized. Particular attention was paid to the effect of liposome-coating on the HCPT-Ch-LZH's water solubility and drug release. The results demonstrate that the nanocomposite has superior water dispersity and enhanced drug sustained-release performance compared to HCPT-Ch-LZH, indicating that the liposome-coating of drug-LZH nanohybrids is an effective strategy for improving their water dispersity and sustained-release performances. This study presents an efficient strategy for constructing LZH-based drug delivery systems for nonionic and lipophilic medicines.

Preparation of pH-responsive polyurethane nano micelles and their antibacterial application

Considering the differences in pH between bacterial infection microenvironment and normal tissues, a series of pH-responsive drug-release amphiphilic polyurethane copolymers (DPU-g-PEG) have been prepared in this work. Fourier transform infrared (FT-IR) spectroscopy and 1H NMR was selected to detect the structure of the condensed polymers. The DPU-g-PEG amphiphilic copolymers could form stable micelles with a hydrophilic shell of polyethylene glycol (PEG) and a hydrophobic core of polylactic acid (PLA). We loaded a model drug called triclosan onto DPU-g-PEG micelles and studied how pH affects their particle size, Zeta potential, and drug release performance. The results revealed that when exposed to acidic conditions, the surface potential of DPU-g-PEG micelles changed, the micelles’ particle size increased, and the drug release performance was significantly enhanced. These results suggested that the micelles prepared in this study can release more antibacterial substances at sites of bacterial infection. Meanwhile, we also investigated the impact of different ratios of soft and hard segments on the properties of micelles, and the results showed that the pH responsiveness of micelles was strongest when the ratio of soft segments (PLLA diol + PEG 2000): 1,6-hexamethylene diisocyanate (HDI): 2,6-Bis-(2-hydroxy-ethyl)-pyrrolo[3,4-f]isoindole-1,3,5,7-tetraone (DMA) = 1: 1.2: 0.2. Furthermore, the results of inhibition zone test, minimum inhibitory concentration (MIC), and minimum bactericidal concentration (MBC) all confirmed the antibacterial activity of triclosan-load DPU-g-PEG micelles. In conclusion, the DPU-g-PEG micelles produced in this study have the potential to be used as intelligent drug delivery systems in the biomedical field.

Molecular Design and Controlled Self-Assembly of Copolymers as Core-Shell-Corona Nanoparticles for Smarter Tumor Treatment.

Copolymer-based core-shell-corona nanoparticles have attracted more interest for tumor chemotherapy, owing to their unique multifunctionality benefiting from their unique multilevel topological structure in comparison with the conventional core-shell ones. Here, the recent progress in such core-shell-corona nanoparticle-based drug delivery systems (DDSs) in tumor chemotherapy was reviewed, focusing on additive functionality of the shell layer for controlled drug release performance from the viewpoints of the molecular design and controlled self-assembly, such as stimuli-responsive gatekeepers, independent loading of active substances, and so on. Moreover, future perspectives have been prospected for smarter tumor treatment.

Desferrioxamine-Laden Nanofibrous Scaffolds with Efficient Angiogenesis for Accelerating Diabetic Wound Healing.

Delayed diabetic wound healing is one of the clinical difficulties, the main reason is the limited angiogenesis ability. Deferriamine (DFO) is an iron chelating agent that can induce angiogenesis, but its application is limited due to its short half-life. Increasing the load and slow release performance of desferriamine is beneficial to accelerate diabetic wound healing. In this study, we developed collagen (Col)-graphene oxide (GO) and (1% w/w) DFO-loaded nanofiber electrospinning scaffolds (DCG) using the electrospinning technique. We tested the physicochemical properties, drug release performance, and vascularization biological function of the scaffolds, and finally evaluated the promotion of full-thickness wound healing in the diabetic rat models. The results showed that DCG scaffolds have good mechanical properties and water-holding capacity and can release DFO continuously for 14 days. In vitro, the novel DCG scaffold exhibited good biocompatibility, with the up-regulation at the gene level of VEGF and its regulator HIF-1α, promoters of angiogenesis. This was verified in vivo, as the scaffold enhanced granulation tissue formation and improved neovascularization, thereby accelerating wound healing when applied to full-thickness defects on the back of diabetic rats. The DCG nanofiber scaffold prepared in this study has good biocompatibility and vascularization ability, and improves the microenvironment in vivo, and has a good application prospect in diabetic wound repair.

An investigation into the effects of ink formulations of semi-solid extrusion 3D printing on the performance of printed solid dosage forms.

Semi-solid extrusion (SSE) 3D printing has recently attracted increased attention for its pharmaceutical application as a potential method for small-batch manufacturing of personalised solid dosage forms. It has the advantage of allowing ambient temperature printing, which is especially beneficial for the 3D printing of thermosensitive drugs. In this study, the effects of polymeric compositions (single hydroxypropyl methylcellulose (HPMC) system and binary HPMC + polyvinylpyrrolidone (PVP) system), disintegrant (silicon oxide (SiO2)), and active pharmaceutical ingredients (tranexamic acid (TXA) and paracetamol (PAC)) on the printability of semisolid inks and the qualities of SSE printed drug-loaded tablets were investigated. Printability is defined by the suitability of the material for the process in terms of its physical properties during extrusions and post-extrusion, including rheology, solidification time, avoiding slumping, etc. The rheological properties of the inks were investigated as a function of polymeric compositions and drug concentrations and further correlated with the printability of the inks. The SSE 3D printed tablets were subjected to a series of physicochemical properties characterisations and in vitro drug release performance evaluations. The results indicated that an addition of SiO2 would improve 3D printing shape fidelity (e.g., pore area and porosity) by altering the ink rheology. The pores of HPMC + PVP + 5PAC prints completely disappeared after 12 hours of drying (pore area = 0 mm2). An addition of SiO2 significantly improved the pore area of the prints which are 3.5 ± 0.1 mm2. It was noted that the drug release profile of PAC significantly increased (p < 0.05) when additive SiO2 was incorporated in the formulation. This could be due to a significantly higher porosity of HPMC + PVP + SiO2 + PAC (70.3 ± 0.2%) compared to HPMC + PVP + PAC (47.6 ± 2.1%). It was also likely that SiO2 acted as a disintegrant speeding up the drug release process. Besides, the incorporation of APIs with different aqueous solubilities, as well as levels of interaction with the polymeric system showed significant impacts on the structural fidelity and subsequently the drug release performance of 3D printed tablets.

Preparation of implantable drug carrier-ordered porous HA/β-TCP composite

HA/?-TCP composite with good biocompatibility and bioactivity had received attention in the field of implantable drug carrier. In order to improve its drug release performance, HA/?-TCP was prepared using low-temperature precipitation method by adjusting pH value and ordered porous morphology were designed and obtained using template method. Using IBU as the drug model, in vitro drug simulation release experiments were conducted on this materia. With increase of pH value, the IBU-loading capacity of this composite gradually decreased, and at a pH value of 6, the IBU-loading capacity could reach 101.3mg/g. The in vitro simulated IBU release experiment indicated that during the rapid release stage of IBU, the ordered porous composite improved sudden drug release phenomenon to varying degrees and all the composites showed good slow-release performance. The composite obtained at a pH of 6 exhibited the best release of IBU, with a cumulative release rate of 86.35%.

Engineering polyvinyl alcohol microspheres with capability for use in photothermal/chemodynamic therapy for enhanced transarterial chemoembolization.

Transarterial chemoembolization (TACE) is widely recognized as a non-surgical treatment approach for advanced liver cancer, combining chemotherapy with the blockage of blood vessels supplying the tumor. To enhance the efficacy of TACE and address chemotherapy resistance, there is growing interest in the development of multifunctional embolic microspheres. In this study, multifunctional PVA microspheres, which encapsulate MIT as a chemotherapeutic drug, PPY as a photothermal agent, and Fe3O4 as a chemodynamic therapy agent, were prepared successfully. The results demonstrated that the developed multifunctional PVA microspheres not only exhibit favorable drug release, photothermal therapy, and chemodynamic therapy performance, but also show a promising synergistic therapeutic effect both in vitro and in vivo. Consequently, the engineered multifunctional PVA microspheres hold tremendous promise for enhancing TACE effectiveness and have the potential to overcome limitations associated with traditional liver cancer treatments.

Evaluation of drug release, mucoadhesive and viscoelastic performances of Netildex gel versus an antibiotic‐steroid combination system

Purpose: The poor bioavailability and therapeutic response exhibited by conventional antibiotic‐steroid ophthalmic solutions due to rapid precorneal elimination of the drug may be overcome using a gel systems. Netildex gel is a preservative‐free product based on netilmicin and dexamethasone indicated for the treatment of inflammatory ocular conditions of the anterior segment and ocular adnexa including post‐cataract surgery. The current investigation evaluated the in vitro drug release, viscosity and mucoadhesion profile of Netildex gel in comparison to a gel matrix with regard to steroid and antibiotic delivery.Methods: In vitro drug release was assessed using Franz‐type diffusion cells, under sink condition, exploiting a simulated tear solution (STS) as dissolution medium and a regenerated cellulose membrane. Evaluation of mucoadhesive and viscoelastic properties were performed by texture analyzer TA‐XT2 and rheometer.Results: The dexamethasone and netilmicin release curves in Netildex gel exhibited a better sustained and controlled pattern over an extended time period (48 h) with respect to another gel system containing anti‐inflammatory and antibiotic drugs. The results were expressed as cumulative percentage of drug release and the antibiotics‐release kinetics from the polymeric matrix, evaluated by different mathematical models. The determination of detachment force demonstrated a significant mucoadhesive strength of Netildex gel compared to mucin. Moreover, rheological analysis of Netildex gel highlighted a strong pseudo‐plastic behaviour under shear strain due to its formulation features.Conclusions: Overall, Netildex gel exhibits a sustained and controlled drug release of both dexamethasone and netilmicin from polymeric matrix thanks to its viscoelastic and mucoadhesive properties allowing to prolong drug residence time on the ocular surface. These data support the reduced administration frequency while maintaining the same efficacy and simultaneously favouring patients' compliance [1].Reference1. Mencucci R. et al. Adv Ther (2022) 39: 5474–5486.

Evaluation of sustained drug release performance and osteoinduction of magnetron-sputtered tantalum-coated titanium dioxide nanotubes.

Modifying the drug-release capacity of titanium implants is essential for maintaining their long-term functioning. Titanium dioxide nanotube (TNT) arrays, owing to their drug release capacity, are commonly used in the biomaterial sphere. Their unique half open structure and arrangement in rows increase the drug release capacity. However, their rapid drug release ability not only reduces drug efficiency but also produces excessive local and systemic deposition of antibiotics. In this study, we designed a tantalum-coated TNT system for drug-release optimization. A decreased nanotube size caused by the tantalum nanocoating was observed through SEM and analyzed (TNT: 110 nm, TNT-Ta1: 80 nm, TNT-Ta3: 40 nm, TNT-Ta5: 20 nm, TNT-Ta7: <5 nm). XPS analysis revealed the distribution of the chemical components, especially that of the tantalum element. In vitro experiments showed that the tantalum nanocoating enhanced cell proliferation; in particular, TNT-Ta5 possessed the best cell viability (about 1.18 of TNT groups at 7d). It also showed that the tantalum nanocoating had a positive effect on osteogenesis (especially TNT-Ta5 and TNT-Ta7). Additionally, hydrophilic/hydrophobic drug (vancomycin/raloxifene) release results indicated that the TNT-Ta5 group possessed the most desirable sustained release capacity. Moreover, in this drug release system, the hydrophobic drug showed more sustained release capacity than the hydrophilic drug (vancomycin: sustained release for more than 48 h, raloxifene: sustained release for more than 168 h). More importantly, TNT-Ta5 is proved to be an appropriate drug release system, which possesses cytocompatibility, osteogenic capacity, and sustained drug release capacity.

PEO-b-PCL/Tween 80/cyclodextrin systems: from bioinspired fabrication to possible nasal administration of ropinirole hydrochloride.

In this study, we designed and developed systems composed of poly(ethylene-oxide)-b-poly(ε-caprolactone) block copolymers of different molecular weights and compositions, non-ionic surfactant, and cyclodextrins. The innovation of this study lies in the combination of these diverse biomaterials to create biomimetic and bioinspired drug delivery supramolecular structures. The systems were formed by the thin-film hydration method. Extensive physicochemical and morphological characterization was conducted using differential scanning calorimetry, light scattering techniques, microcalorimetry analysis, high-resolution ultrasound spectroscopy, surface tension measurements, fluorescence spectroscopy, cryogenic transmission electron microscopy images, and in vitro cytotoxicity evaluation. These innovative hybrid nanoparticles were found to be attractive candidates as drug delivery systems with unique properties by encompassing the physicochemical and thermotropic properties of both classes of materials. Subsequently, Ropinirole hydrochloride was used as a model drug for the purpose of this study. These systems showed a high RH content (%), and in vitro diffusion experiments revealed that more than 90% of the loading dose was released under pH and temperature conditions that simulate the conditions of the nasal cavity. Promising drug release performance was observed with all tested formulations, worth further investigation to explore both ex vivo permeation through the nasal mucosa and in vivo performance in an experimental animal model.

Fabrication of poly(β-amino ester) and hyaluronic acid based pH responsive nanocomplex as an antibiotic release system

World Health Organization (WHO) warns about antimicrobial resistance (AMR) considered as the most serious threats to global health, food security, and development. There are various efforts for elimination of this serious issue. These efforts include education of individuals, new policies, development of new antimicrobials and new materials for effective delivery. Novel drug delivery systems with ability of local and on-demand delivery are one of the promising approaches for prevention of AMR. In this regard, a pH-responsive antibiotic delivery system based on pH-responsive poly(β-amino ester) (PBAE) and enzyme responsive hyaluronic acid (HA). The polymeric nanocomplexes were obtained via electrostatic complexation of PBAE and HA in the presence of a model antibiotics, colistin and vancomycin. The particle sizes at pH 7.4 were determined in the range of 131–730 nm and 120–400 nm by DLS and STEM, respectively. When pH was switched from 7.4 to 5.5, the hydrodynamic diameter increased 2.5–32 fold. The drug release performances were tested using FITC-labeled antibiotics via fluorescence spectroscopy. The nanocomplexes released the drugs more at pH 5.5 compared to pH 7.4. Antibacterial activity of the system was evaluated on various bacteria. The nanocomplex loaded with the antibiotics exhibited significantly greater efficacy against E. coli and S. aureus.

Biomimetic Gradient Hydrogels with High Toughness and Antibacterial Properties.

Traditional hydrogels, as wound dressings, usually exhibit poor mechanical strength and slow drug release performance in clinical biomedical applications. Although various strategies have been investigated to address the above issues, it remains a challenge to develop a simple method for preparing hydrogels with both toughness and controlled drug release performance. In this study, a tannic acid-reinforced poly (sulfobetaine methacrylate) (TAPS) hydrogel was fabricated via free radical polymerization, and the TAPS hydrogel was subjected to a simple electrophoresis process to obtain the hydrogels with a gradient distribution of copper ions. These gradient hydrogels showed tunable mechanical properties by changing the electrophoresis time. When the electrophoresis time reached 15 min, the hydrogel had a tensile strength of 368.14 kPa, a tensile modulus of 16.17 kPa, and a compressive strength of 42.77 MPa. It could be loaded at 50% compressive strain and then unloaded for up to 70 cycles and maintained a constant compressive stress of 1.50 MPa. The controlled release of copper from different sides of the gradient hydrogels was observed. After 6 h of incubation, the hydrogel exhibited a strong bactericidal effect on Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli, with low toxicity to NIH/3T3 fibroblasts. The high toughness, controlled release of copper, and enhanced antimicrobial properties of the gradient hydrogels make them excellent candidates for wound dressings in biomedical applications.