Drug Release Capacity Research Articles

Low-cost fabrication of digital light processing 3D printed conical microneedles for biomedical applications

The 3D printing of microneedles has become an emerging area of research focus due to its ability to rapidly create microneedle arrays with parametrically variable geometry and composition. Through direct fabrication or via replica molding, 3D printed microneedles can facilitate iterative array assessment and act as a screening tool to quickly establish optimal parameters for tissue insertion and capacity for biomarker monitoring or drug release. However, the widespread adoption of 3D printing by microneedle array researcher group faces multiple barriers: (1) Investment in 3D printing systems that are traditionally associated with high-resolution pose a significant financial cost, (2) Current high-resolution printing methods are often slow and not conducive to rapid manufacturing, (3) Material selection can be limited in some ‘proprietary’ 3D printing systems (e.g. CLIP, SLA, or 2PP), (4) Given the multidisciplinary nature of the microneedle-field, researchers may not have the expertise to optimize printing parameters for a given material or printer. This work explores how ultra-low-cost digital light processing (DLP) printers can rapidly produce functional microneedle arrays for a variety of purposes, whether direct print, master mold production, or creation of coated microneedles, at a fraction of the cost of currently used systems. Further, this work highlights that high quality microneedle arrays can be created using DLP printing methods with reliability exceeding 98 %, tip radii on the order of 30 µm, and with appropriate parameter input optimization, high quality microneedle arrays can be fabricated that express desirable characteristics for multiple forms of solid microneedle array production.

Ferric Ions Crosslinked Hyaluronic Acid Beads: Potentials for Drug Delivery Use

ABSTRACT Introduction and purpose: Despite the attractive properties of hyaluronic acid (HA), The preparation of HA beads is still challenging. This article reports the preparation of pH-sensitive gel HA beads. The ionic gelation method was used to prepare the HA gel beads using ferric ions. This cross-linking type is based on forming coordination bonds, which enhance the mechanical properties of the prepared beads. Methods: The developed beads were characterized using Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC). Scanning electron microscopy (SEM) examined the bead's morphology. Furthermore, the potential of HA gel beads as an oral drug delivery system was investigated using metformin as a hydrophilic model drug. The entrapment efficiency and in vitro, release, and release kinetics were evaluated. The crosslinking density and HA concentration effect on drug release and bead swelling capacity under pH 1.2 and 7.4 were also investigated. Results: The entrapment efficiency of metformin in HA beads was found to be 79.56 ± 3.89%. FTIR analysis indicated the ionic interaction between ferric ions and the carboxylic groups on the HA molecule. At the same time, there was no substantial interaction between metformin and the polymeric bead. Morphological evaluation and DSC analysis suggested the successful incorporation of metformin within the beads. The in vitro drug release evaluation showed pH-dependent extended release where the release kinetics followed the first-order mathematical model. Conclusions: This study provides a value-added formulation with the potential for drug delivery use, which can be further investigated for biomedical applications.

Preparation of bacterial cellulose/acrylic acid-based pH-responsive smart dressings by graft copolymerization method

Conventional wound dressings used in trauma treatment have a single function and insufficient adaptability to the wound environment, making it difficult to meet the complex demands of the healing process. Stimuli-responsive hydrogels can respond specifically to the particular environment of the wound area and realize on-demand responsive release by loading active substances, which can effectively promote wound healing. In this paper, BC/PAA-pH responsive hydrogels (BPPRHs) were prepared by graft copolymerization of acrylic acid (AA) to the end of the molecular chain of bacterial cellulose (BC) network structure. Antibacterial pH-responsive ‘smart’ dressings were prepared by loading curcumin (Cur) onto the hydrogels. Surface morphology, chemical groups, crystallinity, rheological, and mechanical properties of BPPRHs were analyzed by different characterization methods. The drug release behavior under different physiological conditions and bacteriostatic properties of BPPRH-Cur dressings were also investigated. The results of structural characterization and performance studies show that the hydrogel has a three-dimensional mesh structure and can respond to wound pH in a ‘smart’ drug release capacity. The drug release behavior of the BPPRH-Cur dressings under different environmental conditions conformed to the logistic and Weibull kinetic models. BPPRH-Cur displayed good antimicrobial activity against common pathogens of wound infections such as E. coli, S. aureus, and P. aeruginosa by destroying the cell membrane and lysing the bacterial cells. This study lays the foundation for the development of new pharmaceutical dressings with positive health, economic and social benefits.

Study of Manipulative In Situ Pore-Formation upon Polymeric Coating on Cylindrical Substrate for Sustained Drug Delivery.

Herein, the micro-porous polylactic acid coating applied on the surface of the cylindrical substrate is fabricated by a novel in situ pore-formation strategy based on the combinational effect of breath figure (BF) and vapor-induced phase separation (VIPS) processes. Under the condition of high environmental humidity, solvent pair of chloroform and dimethylformamide is employed for post-treatment onto pre-formed PLA coating to induce the pore-formation following the mechanism of BF and VIPS, respectively. A composite porous structure with both cellular-like and bi-continuous network morphologies is obtained. By tunning the experimental factors including the ratio of the solvent pair, environmental humidity, and temperature, morphological manipulation upon the pore morphology can be facilely achieved based on the control of mechanism transition between BF and VIPS. Paclitaxel is used as a model drug and loaded into the porous coating by the wicking effect of post-immersion. Coatings with different morphological features show varying drug loading and release capacities. The 28-day release test reveals dynamic release profiles between different coating samples, with the total release rate ranging from 35.70% to 79.96%. Optimal loading capacity of 19.28µg cm-2 and 28-day release rate of 35.70% are achieved for the coating with composite BF-VIPS structure. This research established a cost-efficient strategy with high flexibility in the structural manipulation concerning the construction of drug-eluting coating with the feature of manipulative drug delivery.

PH-responsive chitosan-mediated spherical mesoporous silica microspheres for high loading and controlled delivery of 5-Fluorouracil

The objective of this study is to develop a drug carrier to overcome the inherent drawbacks of 5-Fluorouracil (5-Fu), including low bioavailability, short half-life, and systemic toxicity. In the present work, mesoporous silica nanoparticles (MSNs) capped by chitosan (CS) to encapsulate 5-Fu (5-Fu MSNs/CS) were fabricated by the sol-gel process, ultrasonic impregnation, and emulsion cross-linking. The 5-Fu MSNs/CS microspheres exhibit pH-responsive drug release and remarkable drug encapsulation capacity, as well as perfect sphericity, high specific surface area (680.62 cm2/g), and uniform particle size (2.64 ± 0.05 μm). The drug-loading content and encapsulation efficiency are 14.12 ± 0.53 % and 82.21 ± 2.13 %, respectively. The cumulative release of 5-Fu from MSNs/CS microspheres is fast and sustained at pH 5.0 (89.56 ± 0.97 %) compared to that at pH 7.4 (57.88 ± 0.91 %) in 96 h, and it is Fickian diffusion controlled. In conclusion, the MSNs/CS microspheres prepared in this study could be potential carriers for 5-Fu delivery.

Antibacterial and antibiofilm potentials of vancomycin-loaded niosomal drug delivery system against methicillin-resistant Staphylococcus aureus (MRSA) infections

The threat of methicillin-resistant Staphylococcus aureus (MRSA) is increasing worldwide, making it significantly necessary to discover a novel way of dealing with related infections. The quick spread of MRSA isolates among infected individuals has heightened public health concerns and significantly limited treatment options. Vancomycin (VAN) can be applied to treat severe MRSA infections, and the indiscriminate administration of this antimicrobial agent has caused several concerns in medical settings. Owing to several advantageous characteristics, a niosomal drug delivery system may increase the potential of loaded antimicrobial agents. This work aims to examine the antibacterial and anti-biofilm properties of VAN-niosome against MRSA clinical isolates with emphasis on cytotoxicity and stability studies. Furthermore, we aim to suggest an effective approach against MRSA infections by investigating the inhibitory effect of formulated niosome on the expression of the biofilm-associated gene (icaR). The thin-film hydration approach was used to prepare the niosome (Tween 60, Span 60, and cholesterol), and field emission scanning electron microscopy (FE-SEM), an in vitro drug release, dynamic light scattering (DLS), and entrapment efficiency (EE%) were used to investigate the physicochemical properties. The physical stability of VAN-niosome, including hydrodynamic size, polydispersity index (PDI), and EE%, was analyzed for a 30-day storage time at 4 °C and 25 °C. In addition, the human foreskin fibroblast (HFF) cell line was used to evaluate the cytotoxic effect of synthesized niosome. Moreover, minimum inhibitory and bactericidal concentrations (MICs/MBCs) were applied to assess the antibacterial properties of niosomal VAN formulation. Also, the antibiofilm potential of VAN-niosome was investigated by microtiter plate (MTP) and real-time PCR methods. The FE-SEM result revealed that synthesized VAN-niosome had a spherical morphology. The hydrodynamic size and PDI of VAN-niosome reported by the DLS method were 201.2 nm and 0.301, respectively. Also, the surface zeta charge of the prepared niosome was − 35.4 mV, and the EE% ranged between 58.9 and 62.5%. Moreover, in vitro release study revealed a sustained-release profile for synthesized niosomal formulation. Our study showed that VAN-niosome had acceptable stability during a 30-day storage time. Additionally, the VAN-niosome had stronger antibacterial and anti-biofilm properties against MRSA clinical isolates compared with free VAN. In conclusion, the result of our study demonstrated that niosomal VAN could be promising as a successful drug delivery system due to sustained drug release, negligible toxicity, and high encapsulation capacity. Also, the antibacterial and anti-biofilm studies showed the high capacity of VAN-niosome against MRSA clinical isolates. Furthermore, the results of real-time PCR exhibited that VAN-niosome could be proposed as a powerful strategy against MRSA biofilm via down-regulation of icaR gene expression.

Design of Thermosensitive Niosomes by Eutectic Mixture of Natural Fatty Acids.

In the current study, a smart release system responsive to temperature was developed to improve the efficiency of tetracycline (TC) in antibacterial therapy. The nanovesicles designed consist of a non-ionic surfactant, SPAN60, cholesterol and a phase change material (PCM) as a thermoresponsive gating material. Niosomes were prepared using an increasing amount of PCM and characterized in terms of size, zeta potential, colloidal stability and thermoresponsive properties. The vesicles that developed were homogenous in size, had good biocompatibility and stability for up to 3 months and demonstrated thermoresponsive behavior. A low drug leakage was observed at 37 °C, while a rapid release occurred at 42 °C, due to the faster diffusion rate of the drug trough the melted PCM. This controllable drug release capacity allows us to avoid premature drug release, minimizing unwanted and toxic effects and ensuring a long retention time in the nanodevice so that it reaches the infected sites. In addition, TC-loaded niosomes were screened to investigate their antibacterial activity against various Gram-positive and Gram-negative bacteria by minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) assays. An interesting temperature-dependent antibacterial activity was observed against some bacterial strains: the niosomes activity against S. epidermis, for example, was improved by the temperature increase, as suggested by a reduction in MIC values from 112.81 to 14.10 μM observed at 37 and 42 °C, respectively. Taken together, the thermoresponsive platform developed allows us to use lower antibiotic amounts while ensuring therapeutic efficacy and, so, will advance the development of a novel antibacterial agent in clinical practice.

Comment on Ma et al.’s “The Preventive Effect of Gentamicin in the Irrigating Solution on Endophthalmitis Caused by Methicillin-Resistant Staphylococcus epidermidis After Phacoemulsification with Intraocular Lens Implantation in Rabbits”

ABSTRACT In their recent publication, the authors explored the preventive effect of gentamicin in the irrigating solution on endophthalmitis caused by methicillin-resistant Staphylococcus epidermidis (MRSE) after phacoemulsification with intraocular lens (IOL) implantation in rabbits. This letter commends the authors for their innovative approach and discusses the potential of chitosan-based intraocular lenses as a future solution for reducing the incidence of endophthalmitis. Chitosan’s natural antibacterial properties, coupled with its capacity for sustained drug release and surface modification, make it a promising material for IOLs. This letter highlights recent advancements and suggests areas for further research to fully realize the potential of chitosan-based IOLs in ocular surgery.

Formulation and Evaluation of Tablets Using the Solvent Evaporation Method to Increase the Solubility of Lansoprazole

The inability to determine sufficient and repeatable bioavailability and/or desirable pharmacokinetic features in humans is one of the biggest obstacles to the oral administration of new medicines. The solubility and absorption of a medicine determine its bioavailability, which in turn determines its therapeutic efficacy. Achieving the target drug concentration in the systemic circulation and ensuring drug biological activity in humans are both affected by solubility. A stomach ulcer has the potential to rip through the stomach lining, the initial section of the small intestine, and possibly even the lower esophagus. Distinct ulcers form in different parts of the intestines; one forms in the duodenum and one in the stomach. Duodenal ulcers are most commonly characterized by upper abdominal pain at night that subsides after eating. Eating might exacerbate the discomfort from a stomach ulcer. Preparing and assessing the pills will yield optimal outcomes. The active component content is 99.90%, as is the active ingredient release rate. Compared to other formulations, solid dispersion tablets performed better in in-vitro tests (98.85%). The optimized formulation (lansoprazole solid dispersion tablets) outperformed the labeled formulation (conventional lansoprazole tablet) in terms of drug-releasing capacity within 6 hours, outperforming both formulations.

Microenvironment Responsive Hydrogel Exerting Inhibition of Cascade Immune Activation and Elimination of Synovial Fibroblasts for Rheumatoid Arthritis Therapy

Rheumatoid arthritis (RA) is a progressive autoimmune disease and drug therapy has been restricted due to poor therapeutic efficacy and adverse effects. In RA synovium, dendritic cells present self-antigens to activate cascade immune pathway. Furthermore, downstream macrophages secrete high levels of pro-inflammatory cytokines; Hyperplasia of activated synovial fibroblasts (FLS) is responsible for hypoxic synovium microenvironment, secretion of cytokines/chemokines and erosion of bone/cartilage tissues. Positive feedback loop of inflammation between macrophages and FLS independent of antigen-presentation is constructed. Herein, an injectable pH-sensitive peptide hydrogel encapsulating siRNA/Methotrexate-polyethyleneimine (siMP, including sip65MP, sip38MP, siCD86MP) and Bismuthene nanosheet/Methotrexate-polyethyleneimine (BiMP) is successfully developed. Among them, siCD86MP reduces protein level of co-stimulatory molecule CD86 while sip65MP and sip38MP separately inhibit NF-κB and MAPK-p38 pathways of macrophages and FLS to suppress secretion of cytokines and MMPs. Meanwhile, reduction in anti-apoptotic property of FLS induced by inhibition of NF-κB pathway has a synergistic effect with photodynamic therapy (PDT) and photothermal therapy (PTT) mediated by BiMP for FLS elimination, effectively ameliorating hypoxic synovium microenvironment. After being injected into synovium, hydrogel responds to acidic microenvironment and serves as a reservoir for sustained drug release and inherent retention capacity of which enables cationic nanoparticles to bypass tissue barrier for precise synovium targeting. This brand-new drug delivery system combines modulating cascade immune pathway from beginning to end by RNAi and eliminating FLS for improving synovium microenvironment by phototherapy together, providing a robust strategy for clinical RA treatment.

Liquid‐Metal‐Loaded Hydrogel with Antibacterial Effect and Sustained Release of Growth Factor for Wound Healing

AbstractMultifunctional medical hydrogels play an important role in wound healing because of their excellent biocompatibility, convenient operation, and drug release capacity. So far, many efforts have been exploited to developing new‐generation hydrogels with distinctive capabilities in promoting wound healing. Herein, the liquid‐metal (LM)‐loaded hydrogels are reported with antibacterial effect under an 808 nm near‐infrared laser irradiation for wound healing therapeutic strategies. The addition of LM droplets enables the hydrogel to control the temperature rise and plays an antibacterial effect with the release of gallium3+ under laser irradiation. Benefiting from the porous network structure of hydrogels, the encapsulated growth factors can be released stably at the wound site. Under the synergistic effect of LM and growth factors in the wound tissue, the hydrogel displays antibacterial features and promotes the regeneration of epithelial tissue and neovascularization, thereby further accelerating wound healing. This hydrogel has proven biosafety and low toxicity in vitro and in vivo. With these advantages, such hydrogel is a promising candidate to be developed as a new medical product for future clinical medicine.

Development of Chlorhexidine-loaded Lipid Nanoparticles Incorporated in a Bioceramic Endodontic Sealer

IntroductionThis study aimed to assess BioRoot RCS (BR) incorporating liposomal chlorhexidine digluconate (CHX) for its antibacterial activity, drug release capacity, and physicochemical properties. MethodsDrug release of CHX liposomal formulations in combination with BR was evaluated spectrophotometrically and through mathematical release models for 30 days. A selected combination was evaluated for antimicrobial properties against Enterococcus faecalis biofilm growth on human dentin. Cytotoxicity was assessed following the ISO 10993-5:2019 standard on days 1, 3, and 7. Physicochemical properties were evaluated through setting time, Fourier transform infrared spectroscopy, solubility, contact angle, and film thickness. ResultsFrom BR, liposomal CHX released up to 7-fold higher CHX than CHX solution (P < .05), following a triphasic drug release pattern compared to the CHX solution, which followed a quasi-Fickian diffusion. BR combined with a selected liposomal CHX completely inhibited E. faecalis biofilm growth compared to the combination of BR with CHX solution and the control group (P < .05). Liposomal CHX decreased the contact angle (P < .05) and solubility but increased cytotoxicity (P < .05) of BR, staying above the ISO threshold. None of the other physicochemical characteristics tested differed from BR (P > .05). ConclusionThis liposomal formulation improved CHX release from BR, enhancing the antibacterial effectiveness. It presents a promising approach for local antibiofilm therapy in endodontics without substantially altering the physicochemical characteristics of BR.

A mesoporous magnetothermal nanopomegranate with acid-tolerant hierarchical structure for remote controlled drug delivery

Developing acid-tolerant magnetothermal nanoplatform with robust drug loading capacity for remote controlled drug release is challenging in the harsh acid environment of stomach. Herein, a nanopomegranate-type magnetothermal controllable drug release platform (FeCo@G@MSN), consisted of magnetothermal convertor (graphene-isolated FeCo nanocrystal core, FeCo@G) and drug reservoir (mesoporous silica, MSN), with acid-tolerant hierarchical structure was developed. Benefiting from the acid tolerance of graphene and MSN, FeCo@G@MSN was stable in 1 M hydrochloric acid for more than 12 h. The nanopomegranate-type hierarchical structure endowed FeCo@G@MSN with high saturation magnetization (114.9 emu/g) to generate a magnetothermal effect and large specific surface area (293.7 m2/g) to provide ample space for drug loading. As a proof of concept, a heat-triggered nitric oxide (NO) precursor was loaded, and NO were controlled released by breaking of S-NO bonds through localized heat derived from magnetothermal effect of FeCo@G, resulting in an inhibition effect towards Helicobacter pylori. A chemotherapeutic drug (doxorubicin, DOX) was also loaded and controlled released by breaking of hydrogen bonds between silica and DOX under remote an alternating magnetic field, thus exhibiting an inhibition effect towards gastric cancer cells. This work provides an efficient strategy to exploit magnetothermal controlled drug release platform and offers inspiration for the treatment of gastric diseases.

Exploring the influence of microstructure and phospholipid type of liposomes on their interaction with lung

Liposome is a promising carrier for pulmonary drug delivery and the nano-sized liposomes have been widely investigated in the treatment of lung diseases. However, there still lack the knowledge of micron-sized liposomes for lung delivery, which have more advantages in terms of drug loading and sustained drug release capacity. The micron-sized liposomes can be classified into multilamellar liposome (MLL) and multivesicular liposome (MVL) according to their microstructure, thus, this study focused on exploring how the micron-sized liposomes with different microstructure and phospholipid composition influence their interaction with the lung. The MLL and MVL were prepared from different types of phospholipids (including soya phosphatidylcholine (SPC), egg yolk phosphatidylcholine (EPC), and dipalmitoyl phosphatidylcholine (DPPC)) with geometric diameter around 5 μm, and their in vitro pulmonary cell uptake, in vivo lung retention and organ distribution were investigated. The results showed that the microstructure of liposomes didn’t affect pulmonary cellular uptake, in vivo lung retention and organ distribution. MLL and MVL prepared with the same phospholipid had similar cellular uptake in both NR8383 cells and A549 cells, and both of them possessed prolonged lung retention and limited distribution in other organs during 72 h. Notably, the phospholipid type presented remarkable influence on liposomes’ interaction with the lung. SPC-based liposomes exhibited higher cellular uptake than the DPPC-based ones in both NR8383 cells and A549 cells, also possessed a better lung retention behavior. In conclusion, this study might provide theoretical knowledge for designing micron-sized liposomes intended for lung delivery.

Anticancer and Antibacterial Properties of Curcumin-Loaded Mannosylated Solid Lipid Nanoparticles for the Treatment of Lung Diseases.

Lung cancer and Mycobacterium avium complex infection are lung diseases associated with high incidence and mortality rates. Most conventional anticancer drugs and antibiotics have certain limitations, including high drug resistance rates and adverse effects. Herein, we aimed to synthesize mannose surface-modified solid lipid nanoparticles (SLNs) loaded with curcumin (Man-CUR SLN) for the effective treatment of lung disease. The synthesized Man-CUR SLNs were analyzed using various instrumental techniques for structural and physicochemical characterization. Loading curcumin into SLNs improved the encapsulation efficiency and drug release capacity, as demonstrated by high-performance liquid chromatography analysis. Furthermore, we characterized the anticancer effect of curcumin using the A549 lung cancer cell line. Cells treated with Man-CUR SLN exhibited an increased cellular uptake and cytotoxicity. Moreover, treatment with free CUR could more effectively reduce cancer migration than treatment with Man-CUR SLNs. Similarly, free curcumin elicited a stronger apoptosis-inducing effect than that of Man-CUR SLNs, as demonstrated by reverse transcription-quantitative PCR analysis. Finally, we examined the antibacterial effects of free curcumin and Man-CUR SLNs against Mycobacterium intracellulare (M.i.) and M.i.-infected macrophages, revealing that Man-CUR SLNs exerted the strongest antibacterial effect. Collectively, these findings indicate that mannose-receptor-targeted curcumin delivery using lipid nanoparticles could be effective in treating lung diseases. Accordingly, this drug delivery system can be used to target a variety of cancers and immune cells.

Mesoporous zinc oxide-based drug delivery system offers an antifungal and immunoregulatory strategy for treating keratitis

Fungal keratitis is a refractory eye disease that is prone to causing blindness. Fungal virulence and inflammatory responses are two major factors that accelerate the course of fungal keratitis. However, the current antifungal drugs used for treatment usually possess transient residence time on the ocular surface and low bioavailability deficiencies, which limit their therapeutic efficacy. In this work, natamycin (NATA)-loaded mesoporous zinc oxide (Meso-ZnO) was synthesized for treating Aspergillus fumigatus keratitis with excellent drug-loading and sustained drug release capacities. In addition to being a carrier for drug delivery, Meso-ZnO could restrict fungal growth in a concentration-dependent manner, and the transcriptome analysis of fungal hyphae indicated that it inhibited the mycotoxin biosynthesis, oxidoreductase activity and fungal cell wall formation. Meso-ZnO also promoted cell migration and exhibited anti-inflammatory role during fungal infection by promoting the activation of autophagy. In mouse models of fungal keratitis, Meso-ZnO/NATA greatly reduced corneal fungal survival, alleviated tissue inflammatory damage, and reduced neutrophils accumulation and cytokines expression. This study suggests that Meso-ZnO/NATA can be a novel and effective treatment strategy for fungal keratitis.

Placenta-anchored tadalafil liposomes rescues intrauterine growth restriction through continuous placental blood perfusion improvement

Physiological or pathological hypoperfusion of the placenta is one of the main causes of intrauterine growth restriction (IUGR) which poses a significant risk to the health of the fetus and newborn. Tadalafil, a 5-type phosphodiesterase inhibitor, has previously been found to improve the symptoms of IUGR in various clinical studies. Unfortunately, its clinical utility is hindered by its limited water solubility, rapid metabolism, and lack of specific distribution in target tissues rendering tadalafil unable to maintain long-term placental perfusion. In this study, iRGD-modified tadalafil-loaded liposomes (iRGD-lipo@Tad) featuring a size of approximately 480 nm were designed to rectify the shortcomings of tadalafil. The prepared iRGD-lipo@Tad exhibited superior stability, sustained drug release capacity, and low cytotoxicity. The fluorescence study, tissue slice study, and drug biodistribution study together demonstrated the placenta-anchored ability of iRGD-modified liposomes. This was achieved by a dual approach consisting of the iRGD-mediated placenta-targeting effect and special particle size-mediated placenta resident effect. The pharmacokinetic study revealed a significant improvement in the in vivo process of tadalafil encapsulated by the iRGD-modified liposomes. In comparison to the tadalafil solution, the peak plasma concentration of iRGD-lipo@Tad was significantly increased, and the area under the curve was increased by about 7.88 times. In the pharmacodynamic study, iRGD-lipo@Tad achieved a continuous and efficient improvement of placental blood perfusion. This was achieved by decreasing the ratio of plasma soluble fms-like tyrosine kinase to placental growth factor and increasing the levels of cyclic guanosine monophosphate and nitric oxide. Consequently, iRGD-lipo@Tad resulted in a significant increase in embryo weight and a reduction in the miscarriage rate of N-Nitro-L-arginine methyl ester-induced IUGR pregnant mice without detectable toxicity. In summary, the nanotechnology-assisted therapy strategy presented here not only overcomes the limitations of tadalafil in the clinical treatment of IUGR but also offers new avenues to address the treatment of other placenta-originated diseases.

Ibuprofen-Loaded Silver Nanoparticle-Doped PVA Gels: Green Synthesis, In Vitro Cytotoxicity, and Antibacterial Analyses.

In contrast to conventional drug delivery systems, controlled drug release systems employ distinct methodologies. These systems facilitate the release of active substances in predetermined quantities and for specified durations. Polymer hydrogels have gained prominence in controlled drug delivery because of their unique swelling-shrinkage behavior and ability to regulate drug release. In this investigation, films with a hydrogel structure were crafted using polyvinyl alcohol, a biocompatible polymer, and silver nanoparticles. Following characterization, ibuprofen was loaded into the hydrogels to evaluate their drug release capacity. The particle sizes of silver nanoparticles synthesized using a green approach were determined. This study comprehensively examined the structural properties, morphological features, mechanical strength, and cumulative release patterns of the prepared films. In vitro cytotoxicity analysis was employed to assess the cell viability of drug-loaded hydrogel films, and their antibacterial effects were examined. The results indicated that hydrogel films containing 5% and 10% polyvinyl alcohol released 89% and 97% of the loaded drug, respectively, by day 14. The release kinetics fits the Korsmeyer-Peppas model. This study, which describes nanoparticle-enhanced polyvinyl alcohol hydrogel systems prepared through a cost-effective and environmentally friendly approach, is anticipated to contribute to the existing literature and serve as a foundational study for future research.

In vitro drug release and cartilage interface lubrication properties of biomimetic polymers

Osteoarthritis is a degenerative disease that is widely found in the elderly population, with a trend towards a younger age group in recent years. In the early stages of arthritis, patients are treated with hyaluronic acid injections and anti-inflammatory drugs. However, it has been found that hyaluronic acid can only play a supportive role and does not have a lubricating effect, and due to the absence of blood vessels, nerves, and lymphatic vessels in the articular cartilage, the oral anti-inflammatory drugs cannot reach the interface of the inflammatory joints adequately, and the drug utilisation rate is low. Herein, we designed and prepared a brush-like bionic lubricant for joint lubrication and drug loading. The poly(2-methyl-2-oxazoline) branched chain was grafted onto the hyaluronic acid main chain by ring-opening polymerisation and graft polymerisation to form a brush-like bionic lubricin containing multiple hydrophilic groups, which was self-assembled to encapsulate the drug by using its multi-branched special structure for drug loading. The friction behaviour tests on the articular cartilage surface showed that the prepared bionic lubricin has excellent lubrication effect, with a minimum friction coefficient of 0.036 close to the lubrication effect of natural synovial fluid, which is mainly due to the hydrophilic groups on its molecular chain that can adsorb the water molecules and form a hydration layer at the cartilage interface, which plays the role of hydration lubrication. In addition, in vitro drug release studies showed that the synthesised drug-loading biomimetic lubricin had a certain drug release capacity, and the maximum drug release rate could reach 77.8 % at 72 h. The synthesis of this bionic lubricant with dual functions of lubrication and drug release provides a new idea for the treatment of osteoarthritis.

Evaluation of lupeol-chitosan nanoparticles infused cellulose acetate membranes for enhanced in-vitro anticancer and antidiabetic activities

This study utilizes the abundance of pharmacologically active compounds found in natural products and concentrates on the promising anticancer agent lupeol (LUP). The limited water solubility and bioavailability of lupeol have limited its therapeutic utility. To test their potential for treating diabetes and cancer, we synthesized lupeol@chitosan (LUP@CS) nanoparticles encapsulated in cellulose acetate (CA) membranes (LUP@CS/CA). Extensive characterization, including Scanning electron microscopy, Thermogravimetric analysis, X-ray photoelectron spectroscopy, and mechanical strength analysis, confirmed the membrane's structural integrity and drug release capacity. Notably, in vitro experiments utilizing A431 human skin cancer cells revealed remarkable anticancer activity, positioning the membrane as a potential novel therapeutic agent for the treatment of skin cancer. Inhibiting carbohydrate-digesting enzymes effectively, as evidenced by IC50 values as low as 54.56 mg/mL, the membrane also exhibited significant antidiabetic potential. These results demonstrate the multifarious potential of the membrane, which offers promise for both the treatment of skin cancer and the management of diabetes, and has significant implications for nano biological applications.