PLGA Research Articles

Development and characterization of solriamfetol-loaded PVA/PLGA electrospun nanofiber membranes: A promising approach for sustained narcolepsy treatment

Narcolepsy presents challenges in medication adherence and delivery, with traditional oral medications not always suitable for patients experiencing unexpected sleep episodes or difficulty in swallowing pills. This study focused on developing a solriamfetol (SF) loaded nanofiber membrane using a polymer blend of polyvinyl alcohol (PVA) and polylactic-co-glycolic acid (PLGA) for the management of narcoleptic patients with non-oral dosage options. The design required synthesis, optimization, characterization, and evaluation of these nanofibers for transdermal drug delivery. Using a Box-Behnken design, the nanofibers were produced via the electrospinning technique, achieving a high drug content of 96.31 ± 1.21 % and entrapment efficiency of 96.18 ± 1.42 %. The in vitro drug release studies demonstrated a prolonged release profile of SF over 24 h, with 97 % ± 2 % of the drug released. The SEM analysis revealed that the surface morphology of the nanofibers was smooth and homogenous, and the average diameter of the SF/PVA/PLGA nanofibers was found to be 150.23 ± 2.50 nm. X-ray diffraction results confirmed the amorphous structure of the nanofibers. The zebrafish embryonic toxicological study did not reveal any signs of toxicity or morphological abnormalities in the developing embryos, indicating that the nanofibers are safe. The results point to the applicability of SF nanofiber membranes in personalized narcolepsy therapy, which improves patients’ quality of life and the efficacy of their treatment. These nanofibers can be given in the form of a transdermal patch to patients for sustained drug delivery, even when they fall asleep or when they cannot take medicines orally.

Silibinin-Loaded Amphiphilic PLGA–Poloxamer Nanoparticles: Physicochemical Characterization, Release Kinetics, and Bioactivity Evaluation in Lung Cancer Cells

Despite its potential against several carcinomas, the pharmacological efficacy of silibinin (SLB) is hampered by poor solubility, absorption, and oral bioavailability. To face these issues, we developed polylactic-co-glycolic acid (PLGA) nanoparticles (NPs) coated with hydrophilic polyethene oxide (PEO) for controlled and targeted SLB delivery. NPs were produced at two different SLB loadings and presented a spherical shape with smooth surfaces and stable size in water and cell culture medium. The encapsulation efficiencies were found to be >84%, and thermal analysis revealed that the SLB was present in an amorphous state within the NPs. In vitro SLB release experiments revealed that at the lowest SLB loading, desorption of the active molecule from the surface or nanoporosities of the NPs mainly dictates release. In contrast, at the highest SLB loading, diffusion primarily regulates release, with negligible contributions from other mechanisms. Cell experiments showed that, compared with the free drug, SLB loaded in the produced NPs significantly increased the bioactivity against H1299, H1975, and H358 cells.

Rapid DNA Repair in Mesenchymal Stem Cells and Bone Regeneration by Nanoparticle-Based Codelivery of Nrf2-mRNA and Dexamethasone.

Directional differentiation is a key factor determining the result of stem cell therapy. Herein, we developed a polyethylenimine (PEI)-coated poly(lactic-co-glycolic) acid (PLGA) nanoparticle (mPDN) carrying both nuclear factor erythroid 2-related factor 2 (Nrf2) mRNA and dexamethasone (Dex) to human mesenchymal stem cells (hMSCs). The combination of Dex and Nrf2-mRNA delivered by mPDN promoted the osteogenic differentiation of hMSCs. In particular, Nrf2-mRNA rapidly reduced the DNA damage caused by ROS due to early and efficient gene expression at 3 h after treatment, which was not achieved in traditional pDNA systems. High and rapid transfection, effective ROS-scavenging effect, and protection of mitochondrial dynamics were observed in hMSCs after treatment with the resulting Nrf2-mPDN. Osteogenic differentiation was also observed in 3D pellets for up to 5 weeks. Finally, the effects of rapid DNA repair in hMSCs by Nrf2-mPDN and on in vivo bone regeneration were evaluated in a rat femoral bone defect model using CT. This study demonstrated the potential of an NP-based codelivery system and efficient transfection of mRNA at early stages in hMSCs for bone regeneration and stem cell therapy.

Dual drug delivery systems based on natural and synthetic polymer particles for isoniazid and rifampicin vehiculization

AbstractThe purpose of this work is the design and characterization of novel systems based on micro and nanoparticles prepared from poly(lactic‐co‐glycolic) acid (PLGA), chitosan (CHT) and gelatin (GEL) for compartmentalization and dual release of rifampicin and isoniazid. The emulsion/evaporation method is employed for the preparation of PLGA based microparticles and nanoparticles. CHT and GEL are used for the preparation of microparticles by spray‐drying. Entrapment efficiencies are in the range of 35%–73% and 5%–29% for rifampicin and isoniazid in PLGA microparticles, respectively. For isoniazid GEL:CHT particles the entrapment efficiencies are within 82%–100%. Isoniazid shows a complete release at acid condition from GEL:CHT particles, while rifampicin release is maintained from GEL:CHT particles or displays an slightly increase from PLGA particles during buffer conditions. Antimycobacterial activity experiments show that the formulations present the ability to inhibit the bacterial growth in comparison with a control culture without treatment. Rifampicin PLGA and isoniazid GEL:CHT microparticles could be used for the preparation of a dual drug delivery system with each antibiotic in a single particulate compartment. GEL:CHT microparticles containing free isoniazid and rifampicin PLGA nanoparticles are a novel two compartment delivery system.

An Adaptive Approach in Polymer-Drug Nanoparticle Engineering using Slanted Electrohydrodynamic Needles and Horizontal Spraying Planes.

The present study focuses on the adaptive development of a key peripheral component of conventional electrohydrodynamic atomisation (EHDA) systems, namely spraying needles (also referred to as nozzles or spinnerets). Needle geometry and planar alignment are often overlooked. To explore potential impact, curcumin-loaded polylactic-co-glycolic acid (PLGA) and methoxypolyethylene glycol amine (PEG)-based nanoparticles were fabricated. To elucidate these technological aspects, a horizontal electrospraying needle regime was adapted, and three formulations containing different polymeric ratios of PLGA: PEG (50:50, 75:25, and 25:75) were prepared and utilised. Furthermore, processing head tip geometries e.g.blunt (a flat needle exit) or slanted (a 45° inclination angle), were subjected to various flow rates (5 µL-100 µL). Successful engineering of curcumin-loaded polymeric nanoparticles (< 150nm) was observed. In-silico analysis demonstrated stable properties of curcumin, PEG and PLGA (molecular docking studies) and fluid flow direction towardsthe Taylor-Cone (also known as the stable jet mode), was shownby the assessment of fluid dynamics simulations in various needle outlets. Curcumin-loaded nanoparticles were characterised using an array of methods including Scanning electron microscopy, Differential scanning calorimetry, Fourier transform infrared spectroscopy, X-ray diffraction, as well as their contact angles, encapsulation efficiencies and finally release patterns. The discrepancy when spraying with blunt and angled needles was evidenced by electron micrographs and deposition patterns. Spraying plumes utilising slanted needles enhanced particle collection efficiency and distribution of resultant atomised structures. In addition to needle design, fine-tuning the applied voltage and flow rate impacted the electrospraying process. The coefficient of variation was calculated as 30.5% and 25.6% for blunt and angled needle outlets, respectively, presenting improved particle uniformity with the employment of angled needle tips (8-G needle at 25 µL). The interplay of processing parameters with the utilisation of a slanted exit at a capillary optimised the spray pattern and formation of desired nanoparticulates. These demonstrate great applicability for controlled deposition and up-scaling processes in the pharmaceutical industry. These advances elaborate on EHDA processes, indicating a more cost-effective and scalable approach for industrial applications, facilitating the generation of a diverse range of particle systems in a controlled and more uniform fashion.

Enhanced Mandibular Bone Repair Using Poly Lactic-co-glycolic Acid Combined with Nanohydroxyapatite Scaffold Loaded by Mesenchymal Stromal/Stem Cells and Curcumin in Male Rats.

This study aimed to investigate the healing effect of a polylactic-co-glycolic acid (PLGA) scaffold containing nanohydroxyapatite (NHA) along with curcumin (CCM), loaded with adipose-derived mesenchymal stem cells (AD-MSCs), on mandibular bone defects. The designed PLGA scaffolds containing NHA were evaluated for their mechanical and structural properties. Forty rats were divided into five groups (n = 8) based on the treatment: Sham, PLGA scaffolds containing NHA, PLGA scaffolds containing NHA + CCM, PLGA scaffolds containing NHA + AD-MSCs, and PLGA scaffolds containing NHA + CCM + AD-MSCs. After 8 weeks' follow-up, mandible bones were isolated for histomorphometry evaluation. Data were analyzed using SPSS version 21, with p-values <0.05 considered statistically significant. SEM evaluation showed that the designed nanocomposite scaffold had 80% porosity. Histomorphometry results indicated a significant difference in osteocyte, osteoblast, bone area, and vascular area parameters in the group treated with scaffolds loaded with AD-MSCs + CCM compared to the other groups (p < 0.05). The PLGA-containing NHA-CCM nanocomposite scaffold demonstrated good porosity and dispersion, suitable for treating bone defects. Rats treated with scaffolds containing AD-MSCs and CCM showed better therapeutic results than the other groups. Further research is needed to evaluate its anti-inflammatory, antioxidant properties, osteogenesis, and therapeutic effects in larger animal models.

Development of Stable and Intensified Mixing Processes for the Precise and Scalable Production of Uniform Drug Delivery Nanocarriers.

Nanocarriers show great promise in drug delivery but face challenges in stability, uniformity, and morphology control. This work introduces an enhanced mixing process to overcome these obstacles, specifically aiming to produce consistently sized poly(lactic-co-glycolic) acid (PLGA) nanoparticles loaded with anti-tumor drugs. By innovatively integrating a pulsation dampener into the microfluidic channels of a continuous flow preparation system, the flow stability of piston pumps is improved nearly tenfold. Consequently, large-scale production of uniformly sized nanoparticles with customizable dimensions is achieved through nanoprecipitation. Furthermore, incorporating terminal double-bond-functionalized poly(lactic-co-glycolic acid)-b-poly(ethylene glycol)-maleimide (PLGA-PEG-Mal) enables these nanoparticles to act as nano-crosslinkers. This facilitates in situ crosslinking with thiolated hyaluronic acid via a spontaneous thiol-ene coupling reaction under physiological conditions, allowing for minimally invasive drug administration and significantly enhancing localized drug retention. The material's degradability in the presence of endogenous enzymes ensures controlled drug release, as demonstrated with the anti-tumor drug doxorubicin (DOX). Validation in a murine breast cancer model shows reduced toxicity and a substantial reduction in tumor weight compared to the free DOX group. These findings confirm the approach's effectiveness for breast cancer treatment and pave the way for innovative solutions in nanomedicine, providing a practical microfluidic mixing system for the design and large-scale production of nanomedicines.

Rifampicin-Loaded PLGA/Alginate-Grafted pNVCL-Based Nanoparticles for Wound Healing

The topical therapy with rifampicin (RF)-based formulations is beneficial for treating postoperative wound infections and to accelerate healing. Despite recent research highlighting the antibiotic’s significant anti-inflammatory properties, limited topical wound healing products are currently available. The present study aimed to prove that the newly synthesized nanoparticles based on grafted alginate and poly(N-vinylcaprolactam) (pNVCL) and poly-lactic-co-glycolic acid (PLGA) contribute to the healing process of a wound. The methods used were at first the synthesis of the copolymer of alginate and pNVCL via grafting from technique and radical polymerization followed by water-in-oil-in water (W/O/W) emulsification; as oil phase PLGA dissolved in dichloromethane (DCM) was used. The formed nanoparticles were than characterized. The loaded RF was determined to be 160 µg/mL for a 20 mg formulation and within a four-hour time frame approximately 10% of the total loaded amount was released. The inhibitory concentrations (IC50) were 192.1 µg/mL for the nanoparticle, 208.8 µg/mL for pure rifampicin, and 718.1 µg/mL for the rifampicin-loaded nanoparticles. Considering the double role rifampicin was used for, the result was considered satisfactory in the way that these formulations could be used predominantly for postoperative wound irrigation in order to avoid infections and to improve healing.

High quality factor, monodisperse micron-sized random lasers based on porous PLGA spheres.

Miniature random lasers with high quality factor are crucial for applications in barcoding, bioimaging, and on-chip technologies. However, achieving monodisperse and size-tunable biocompatible random lasers has been a significant challenge. In this study, we employed poly(lactic-co-glycolic) acid (PLGA), a biocompatible material approved for medical use, as the base material for random lasers. By integrating a dye-doped PLGA solution with a microfluidic system, we successfully fabricated monodisperse and miniature dye-doped PLGA spheres with tunable sizes ranging from 25 to 52 µm. Upon optical pulse excitation, these spheres exhibited strong random lasing emission at 610-640 nm with a threshold of approximately 22 µJ·mm-2. The lasing modes demonstrated a spectral linewidth of 0.2 nm, corresponding to a quality factor of 3100. Fourier transform analysis of the lasing emission revealed fundamental cavity lengths, providing insights into the properties of the random lasers.

Magnesium-Titanium Alloys: A Promising Solution for Biodegradable Biomedical Implants.

Magnesium (Mg) has attracted considerable attention as a biodegradable material for medical implants owing to its excellent biocompatibility, mitigating long-term toxicity and stress shielding. Nevertheless, challenges arise from its rapid degradation and low corrosion resistance under physiological conditions. To overcome these challenges, titanium (biocompatibility and corrosion resistance) has been integrated into Mg. The incorporation of titanium significantly improves mechanical and corrosion resistance properties, thereby enhancing performance in biological settings. Mg-Ti alloys are produced through mechanical alloying and spark plasma sintering (SPS). The SPS technique transforms powder mixtures into bulk materials while preserving structural integrity, resulting in enhanced corrosion resistance, particularly Mg80-Ti20 alloy in simulated body fluids. Moreover, Mg-Ti alloy revealed no more toxicity when assessed on pre-osteoblastic cells. Furthermore, the ability of Mg-Ti-based alloy to create composites with polymers such as PLGA (polylactic-co-glycolic acid) widen their biomedical applications by regulating degradation and ensuring pH stability. These alloys promote temporary orthopaedic implants, offering initial load-bearing capacity during the healing process of fractures without requiring a second surgery for removal. To address scalability constraints, further research is necessary to investigate additional consolidation methods beyond SPS. It is essential to evaluate the relationship between corrosion and mechanical loading to confirm their adequacy in physiological environments. This review article highlights the importance of mechanical characterization and corrosion evaluation of Mg-Ti alloys, reinforcing their applicability in fracture fixation and various biomedical implants.

Partial Protection of Goats against Haemonchus contortus Achieved with ADP-Ribosylation Factor 1 Encapsulated in PLGA Nanoparticles.

Haemonchus contortus (H. contortus), a nematode with global prevalence, poses a major threat to the gastrointestinal health of sheep and goats. In an effort to combat this parasite, a nanovaccine was created using a recombinant ADP-ribosylation factor 1 (ARF1) antigen encapsulated within poly lactic-co-glycolic acid (PLGA). This study aimed to assess the effectiveness of this nanovaccine in providing protection against H. contortus infection. Fifteen goats were randomly divided into three groups. The experimental group received two doses of the PLGA encapsulated rHcARF1 (rHcARF1-PLGA) nanovaccine on days 0 and 14. Fourteen days after the second immunization, both the experimental and positive control groups were challenged with 8000 infective larvae (L3) of H. contortus, while the negative control group remained unvaccinated and unchallenged. At the end of the experiment on the 63rd day, all animals were humanly euthanized. The results showed that the experimental group had significantly higher levels of sera IgG, IgA, and IgE antibodies, as well as increased concentrations of cytokines, such as IL-4, IL-9, IL-17, and TGF-β, compared to the negative control group after immunization. Following the L3 challenge, the experimental group exhibited a 47.5% reduction in mean eggs per gram of feces (EPG) and a 55.7% reduction in worm burden as compared to the positive control group. These findings indicate that the nanovaccine expressing rHcARF1 offers significant protective efficacy against H. contortus infection in goats. The results also suggest the need for more precise optimization of the antigen dose or a reassessment of the vaccination regimen. Additionally, the small sample size limits the statistical rigor and the broader applicability of the findings.

Mechanistic Model for Drug Release from PLGA-Based Biodegradable Implants for In Vitro Release Testing: Development and Validation.

Several factors can affect drug release from polylactide coglycolide (PLGA)-based formulations, including polymer and drug properties, formulation components, manufacturing processes, and environmental in vitro or in vivo conditions. To achieve optimal release profiles for specific drug delivery applications, it is crucial to understand the mechanistic processes that determine drug release from PLGA-based formulations. In the current study, we developed a mechanistic model for the in vitro drug release of PLGA-based solid implants. The model accounts for all known critical quality attributes (CQAs) and considers the most important release rate processes, including water or dissolution medium influx into the porous structure of the implant, initial noncatalytic hydrolysis of PLGA, autocatalytic hydrolysis, dissolution of oligomers and monomers into the aqueous medium, the liberation of the trapped solid drug from the polymer matrix, dissolution of the solid drug into the wetted pore network, diffusion of the dissolved drug out of the implant, and distribution of the dissolved drug into the dissolution medium. The model has been validated using in vitro release data obtained from implants of four drugs (buserelin, afamelanotide, brimonidine, and nafarelin). The model presented in this manuscript provides valuable insights into the kinetics and mechanism of drug release from PLGA-based solid implants and has demonstrated the potential for optimizing formulation design. The in vitro release model, coupled with physiologically based pharmacokinetic (PBPK) modeling, can predict the in vivo performance of implants and can be used to support bioequivalence studies in a drug development program.

3D-printed magnesium-doped micro-nano bioactive glass composite scaffolds repair critical bone defects by promoting osteogenesis, angiogenesis, and immunomodulation

Magnesium ions play an important immune-regulatory role during bone repair. For this study, we prepared micro-nano bioactive glass (MNBG) containing magnesium, which can release magnesium, silicon, and calcium ions and has a positive impact on osteogenic differentiation and vascular regeneration. In this study, MgMNBG was compounded and combined with poly(lactic-co-glycolic acid (PLGA) and polycaprolactone (PCL) for 3D printing. Afterwards, the physicochemical properties and bone repair performance of the scaffolds were evaluated throughin vitroandin vivoexperiments. We also investigated the effects of MgMNBG on osteogenic differentiation, immune regulation, and vascular regeneration. The results showed that MgMNBG can inhibit inflammation and promote osteogenesis and angiogenesis by regulating macrophages. PLGA/PCL/MgMNBG scaffolds have good osteogenic and angiogenic effects, and the composite scaffolds have excellent bone repair performance and potential application value.

Macrophage Membrane-Biomimetic Multi-Layered Nanoparticles Targeting Synovial Angiogenesis for Osteoarthritis Therapy.

Osteoarthritis (OA) is an inflammatory and progressive joint disease characterized by angiogenesis-mediated sustained, chronic, and low-grade synovitis. Anti-angiogenesis is emerging as a strategy for attenuating OA progression, but is often compromised by poor targeted drug delivery and immune clearance. Recent studies have identified macrophages formed a "protective barrier" in the lining layer (LL) of synovium, which blocked the communication of joint cavity and sublining layer (SL) of synovium. Inspired by natural mimicry, macrophage membrane-camouflaged drug delivery is explored to avoid immune clearance. Based on the single cell RNA sequencing, the CD34+ synovial cells are identified as "sentinel cells" for synovium angiogenesis. Consequently, CD34 antibody-modified macrophage membraneis constructed to target new angiogenesis. Hence, a biomimetic multi-layered nanoparticle (NP) is developed that incorporates axitinib-loaded poly(lactic-co-glycolic) acid (PLGA) with CD34 antibody modified macrophage membrane (Atb@NP@Raw@CD34) to specifically deliver axitinib (Atb) to the SL and sustain inhibiting angiogenesis without immune elimination. It is found that the Atb@NP@Raw@CD34 can pass through macrophage "barrier", specifically targeting CD34+ cells, continuously releasing Atb and anti-angiogenesis in OA synovitis. Furthermore, in vivo data demonstrated that Atb@NP@Raw@CD34 can attenuate joint degeneration by inhibiting synovium angiogenesis-mediated synovitis. In conclusion, local injection of Atb@NP@Raw@CD34 presents a promising approach for clinically impeding OA progression.

Silver Nanoparticles and Simvastatin-Loaded PLGA-Coated Hydroxyapatite/Calcium Carbonate Scaffolds.

The need to develop synthetic bone substitutes with structures, properties, and functions similar to bone and capable of preventing microbial infections is still an ongoing challenge. This research is focused on the preparation and characterization of three-dimensional porous scaffolds based on hydroxyapatite (HA)-functionalized calcium carbonate loaded with silver nanoparticles and simvastatin (SIMV). The scaffolds were prepared using the foam replica method, with a polyurethane (PU) sponge as a template, followed by successive polymer removal and sintering. The scaffolds were then coated with poly(lactic-co-glycolic) acid (PLGA) to improve mechanical properties and structural integrity, and loaded with silver nanoparticles and SIMV. The scaffolds were characterized by X-ray powder diffraction (XRD), field emission scanning electron microscopy (FE-SEM), ATR FT-IR, and silver and SIMV loading. Moreover, the samples were analyzed by Brillouin and Raman microscopy. Finally, in vitro bioactivity, SIMV and silver release, and antimicrobial activity against Staphylococcus aureus and Staphylococcus epidermidis were evaluated. From the Brillouin spectra, samples showed characteristics analogous to those of bone tissue. They exhibited new hydroxyapatite growth, as evidenced by SEM, and good antimicrobial activity against the tested bacteria. In conclusion, the obtained results demonstrate the potential of the scaffolds for application in bone repair.

Multi-loaded PLGA microspheres as neuroretinal therapy in a chronic glaucoma animal model.

This work focused on the co-encapsulation and simultaneous co-delivery of three different neuroprotective drugs in PLGA (poly(lactic-co-glycolic acid) microspheres for the treatment of glaucoma. For formulation optimization, dexamethasone (anti-inflammatory) and ursodeoxycholic acid (anti-apoptotic) were co-loaded by the solid-in-oil-in-water emulsion solvent extraction-evaporation technique as a first step. The incorporation of a water-soluble co-solvent (ethanol) and different amounts of dexamethasone resulted critical for the encapsulation of the neuroprotective agents and their initial release. The optimized formulation was obtained with 60mg of dexamethasone and using an 80:20 dichloromethane:ethanol ratio. In the second step in the microencapsulation process, the incorporation of the glial cell line-derived neurotrophic factor (GDNF) was performed. The final prototype showed encapsulation efficiencies for each component above 50% with suitable properties for long-term application for at least 3months. Physicochemical studies were performed by SEM, TEM, DSC, XRD, and gas chromatography. The evaluation of the kinetic release by the Gallagher-Corrigan analysis with Gorrasi correction helped to understand the influence of the co-microencapsulation on the delivery of the different actives from the optimized formulation. The final prototype was tested in a chronic glaucoma animal model. Rats received two intravitreal injections of the neuroprotective treatment within a 24-week follow-up study. The proposed formulation improved retinal ganglion cell (RGC) functionality examined by electroretinography. Also, it was able to maintain a neuroretinal thickness similar to that of healthy animals scanned by in vivo optical coherence tomography, and a higher RGC count on histology compared to glaucomatous animals at the end of the study.

Nanospheres as the delivery vehicle: novel application of Toxoplasma gondii ribosomal protein S2 in PLGA and chitosan nanospheres against acute toxoplasmosis.

Toxoplasma gondii (T. gondii) is a zoonotic disease that poses great harm to humans and animals. So far, no effective T. gondii vaccine has been developed to provide fully protection against such parasites. Recently, numerous researches have focused on the use of poly-lactic-co-glycolic acid (PLGA) and chitosan (CS) for the vaccines against T. gondii infections. In this study, we employed PLGA and CS as the vehicles for T. gondii ribosome protein (TgRPS2) delivery. TgRPS2-PLGA and TgRPS2-CS nanospheres were synthesized by double emulsion solvent evaporation and ionic gelation technique as the nano vaccines. Before immunization in animals, the release efficacy and toxicity of the synthesized nanospheres were evaluated in vitro. Then, ICR mice were immunized intramuscularly, and immune protections of the synthesized nanospheres were assessed. The results showed that TgRPS2-PLGA and TgRPS2-CS nanospheres could induce higher levels of IgG and cytokines, activate dendritic cells, and promote the expression of histocompatibility complexes. The splenic lymphocyte proliferation and the enhancement in the proportion of CD4+ and CD8+ T lymphocytes were also observed in immunized animals. In addition, two types of nanospheres could significantly inhabit the replications of T. gondii in cardiac muscles and spleen tissues. All these obtained results in this study demonstrated that the TgRPS2 protein delivered by PLGA or CS nanospheres provided satisfactory immunoprotective effects in resisting T. gondii, and such formulations illustrated potential as prospective preventive agents for toxoplasmosis.

Ultrasound-mediated PLGA-PEI Nanobubbles Carrying STAT6 SiRNA Enhances NSCLC Treatment via Repolarizing Tumor-associated Macrophages from M2 to M1 Phenotypes.

Tumor-associated macrophages (TAMs) are crucial for non-small cell lung cancer (NSCLC) development. In this study, polylactic acid-co-glycolic acid (PLGA)-polyethylenimine (PEI) nanobubbles (NBs) carrying STAT6 siRNA were prepared and combined with ultrasound-mediated nanobubbles destruction (UMND) to silence the STAT6 gene, ultimately repolarizing TAMs from the M2 to the M1 phenotype, treating NSCLC in vitro. PLGA-PEI NBs-siRNA were prepared and characterised, and their respective ultrasound imaging, biological stabilities and cytotoxicities were detected. Transfection efficiency was evaluated by fluorescence microscopy and flow cytometry. Repolarization of THP-1-derived M2-like macrophages was determined by qPCR and flow cytometry. NSCLC cells (A549) were co-cultured with transfected M2-like macrophages or their associated conditioned medium (CM). Western blotting was used to detect STAT6 gene silencing in M2-like macrophages and markers of epithelial and mesenchymal in A549 cells. The proliferation of A549 cells was detected using CCK-8 and cell colony formation assays. Transwell assays were used to detect the migration and invasion of A549 cells. PLGA-PEI NBs-siRNA had an average size of 223.13 ± 0.92 nm and a zeta potential of about -5.59 ± 0.97 mV. PLGA-PEI NBs showed excellent ultrasonic imaging capability in addition to biological stability to protect siRNA from degradation. UMND enhanced PLGA-PEI NBs-STAT6 siRNA transfection in M2-like macrophages, which made M2-like macrophages repolarize to M1-like macrophages and prevented proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) in A549 cells. UMND enhanced PLGA-PEI NBs-STAT6 siRNA to repolarize TAMs from the M2 to the M1 phenotype, thus treating NSCLC. These findings provide a promising therapeutic approach for enhancing NSCLC immunotherapy.

Investigation of the Impact of Manufacturing Methods on Protein-Based Long-Acting Injectable Formulations: A Comparative Assessment for Microfluidics vs. Conventional Methods.

Therefore, rhCCL22-loaded poly(lactic-co-glycolic) acid (PLGA) microparticles were prepared by conventional homogenization and microfluidics methods. The resulting microparticles were analyzed comparatively, focusing on critical quality attributes such as microparticle size, size distribution, morphology, drug encapsulation efficiency, release kinetics, and batch-to-batch variations in relation to the manufacturing method. Our results demonstrated that the conventional method resulted in microparticles with denser surface porosity and wider size distribution as opposed to microparticles prepared by the microfluidics method, which could contribute to a significant difference in the drug-release kinetics. Additionally, our findings indicated minimal variation within batches for the microparticles prepared by the microfluidics method. Overall, this study highlights the comparative assessment of several critical quality attributes and batch variations associated with the manufacturing methods of protein-loaded microparticles which is crucial for ensuring consistency in efficacy, regulatory compliance, and quality control in the drug formulation manufacturing process.

Development and Characterization of Oxiconazole Loaded Plga Nanogel.

The goal of the current study is to develop and improve polylactic co-glycolic acid (PLGA) loaded with oxiconazole nanogel for topical application. Oxiconazole Nanoprecipitation was used to create the nanoparticles method using PLGA and acetone. The point prediction method served as the foundation for the ideal oxiconazole nanoparticle composition using the Minitab®21 software, three levels two factors (32 ). The optimized composition of oxiconazole nanoparticle showed a particle size of 185 ± 0.5nm with an entrapment efficiency of 95.2 ± 0.09%. Using chitosan, a naturally occurring polymer, the ideal oxiconazole nanoparticle composition was further transformed into a gel formulation. The developed topical nano gel formulation underwent additional evaluations for antifungal, drug release, permeability, and nano gel characterization. The developed oxiconazole nanogel formulation had the ideal drug content, pH, viscosity, and spreadability. The results of the medication release and penetration investigation showed that Oxiconazole released slowly (74.06 ± 0.5%) with significantly enhanced permeation across Franz diffusion cell using membrane. The antifungal ex-vivo study and skin irritancy study of nanogel results would conclude higher activity of oxiconazole nano gel. According to the overall analysis of the data, oxiconazole nanogel is the best delivery method for treating fungal infections on the skin.