PLGA Research Articles

Biodegradable Alternatives to Plastic in Medical Equipment: Current State, Challenges, and the Future

The use of plastic products or components in medical equipment and supplies results in challenges in terms of environmental sustainability and waste management for disposable, non-recyclable, and non-biodegradable materials. Medical plastic waste includes items ranging from syringes, tubing, intravenous (IV) bags, packaging, and more. Developing biodegradable replacements to petroleum-based plastics in medical equipment has not yet become an urgent priority, but it is an important endeavor. Examining alternatives involves several key themes, including material selection, testing, validation, and regulatory approval. To date, research includes studies on biodegradable polymers, composite materials, surface modifications, bacterial cellulose, three-dimensional (3D) printing with biodegradable materials, clinical trials and testing, collaboration with industry, regulatory considerations, sustainable packaging for medical devices, and life cycle analysis. The incorporation of bio-based and biodegradable plastics in the healthcare industry holds immense potential for reducing the environmental impact of medical plastic waste. The literature suggests that researchers and industry professionals are actively working towards finding sustainable alternatives that meet the stringent requirements of the medical industry. This paper reviews the efforts made so far to develop biodegradable and sustainable alternatives to plastic in medical equipment using a meta-analysis of resources, which include relevant papers published in English until June 2024. A total of 116 documents were found and screened by three reviewers for relevance. The literature reviewed indicated that various medical uses require plastics due to their unique properties, such as having strength and flexibility; being lightweight; and being able to prevent bacterial contamination. Among the alternatives, polycaprolactone (PCL), polylactic-co-glycolic acid (PLGA), starch-based acid, and polybutyric acid (PBS) have demonstrated favourable outcomes in terms of biocompatibility, safety, and efficacy. Additionally, a set of approaches to overcome these barriers and strategies is discussed alongside potential future solutions. This review aims to catalyze discussions and actions toward a more environmentally sustainable future in the medical industry by providing a comprehensive analysis of the current state, challenges, and prospects of this domain.

In vivo analysis of hybrid hydrogels containing dual growth factor combinations, and skeletal stem cells under mechanical stimulation for bone repair

Bone tissue engineering requires a combination of materials, cells, growth factors and mechanical cues to recapitulate bone formation. In this study we evaluated hybrid hydrogels for minimally invasive bone formation by combining biomaterials with skeletal stem cells and staged release of growth factors together with mechanotransduction. Hybrid hydrogels consisting of alginate and decellularized, demineralised bone extracellular matrix (ALG/ECM) were seeded with Stro-1+ human bone marrow stromal cells (HBMSCs). Dual combinations of growth factors within staged-release polylactic-co-glycolic acid (PLGA) microparticles were added to hydrogels to mimic, in part, the signalling events in bone regeneration: VEGF, TGF-β3, PTHrP (fast release), or BMP-2, vitamin D3 (slow release). Mechanotransduction was initiated using magnetic fields to remotely actuate superparamagnetic nanoparticles (MNP) targeted to TREK1 ion channels. Hybrid hydrogels were implanted subcutaneously within mice for 28 days, and evaluated for bone formation using micro-CT and histology. Control hydrogels lacking HBMSCs, growth factors, or MNP became mineralised, and neither growth factors, HBMSCs, nor mechanotransduction increased bone formation. However, structural differences in the newly-formed bone were influenced by growth factors. Slow release of BMP-2 induced thick bone trabeculae and PTHrP or VitD3 increased bone formation. However, fast-release of TGF-β3 and VEGF resulted in thin trabeculae. Mechanotransduction reversed the trabecular thinning and increased collagen deposition with PTHrP and VitD3. Our findings demonstrate the potential of hybrid ALG/ECM hydrogel–cell–growth factor constructs to repair bone in combination with mechanotransduction for fine-tuning bone structure. This approach may form a minimally invasive reparative strategy for bone tissue engineering applications.

Colon-Targeted Sustained-Release Combinatorial 5-Fluorouracil and Quercetin poly(lactic-co-glycolic) Acid (PLGA) Nanoparticles Show Enhanced Apoptosis and Minimal Tumor Drug Resistance for Their Potential Use in Colon Cancer.

Colorectal cancer (CRC) is the third most common cancer worldwide, acting as a significant public health problem. 5-Fluorouracil (5-FU) is a key chemotherapy for various types of cancer, due to its broad anticancer activity. However, the emergence of drug resistance is a considerable limitation in the clinical application of 5-FU. Quercetin (QC) is proposed as an adjuvant therapy to minimize drug resistance to chemotherapeutics and enhance their pharmacological efficacy. The oral delivery of 5-FU and QC is challenged by poor aqueous solubility of QC and poor cellular permeability of 5-FU. To solve this issue, novel polylactide-co-glycolide (PLGA) combinatorial nanoparticles loading 5-FU and QC were prepared to deliver them directly to the colon. These sustained-release combinatorial nanoparticles recorded a significant decrease in cancer cell proliferation, C-reactive protein (CRP) level, and Interleukin-8 (IL-8) expression by 30.08%, 40.7%, and 46.6%, respectively. The results revealed that this combination therapy may offer a new strategy for the targeted delivery of chemotherapeutics to the colon.

In vitro drug release profiling of Sirolimus polymeric microparticles coated long-acting stents

In the realm of arterial disease interventions, drug-eluting stents (DES) have become a vital therapeutic choice in preventing atherosclerotic plaque formation and restenosis and facilitating vessel healing. Sirolimus-encapsulated poly Lactic-co-Glycolic acid (PLGA) Microparticles (MPs) were developed using solvent evaporation. MPs were freeze-dried with a cryoprotectant and coated on the stent surface using an efficient and reproducible nitrogen-assisted spray coating technique. The MPs displayed a uniform distribution particle size of 4.38 ± 1.1 μm, span value of 0.88 ± 0.02, coating mass transfer efficiency of 13.45 ± 1.1 % on the stent, and a coating time of ≤ 2 min per stent. Post sterilization, the particle size and morphology of the coated stents remained unchanged. Accelerated in vitro drug release profiles were evaluated under different conditions, indicating significant influences based on dissolution methods ranging from 28.2 %±4.3 %, 42.5 %±5.3 %, 76.6 %±4.7 %, and 84.25 %±3.1 % for dialysis bag (DB), vessel simulating flow-through cell (vFTC), flow-through cell (FTC), and sample and separate (SS) technique respectively for 48 h. The drug release mechanism from the coated stents is governed by the combination of the Korsmeyer Peppas and Higuchi models. The developed dissolution method exhibited discriminative effectiveness when evaluated with critical formulation attributes and process parameter variations. The 48 h accelerated drug release studies correlated well with the 6-month real-time release rate with an R2 value of 0.9142 and Pearson’s R2 of 0.9561. Ex-vivo studies demonstrated the permeation of MPs into artery tissues. Stability studies confirmed that MPs coated stents maintained desired properties at 4 °C and 30 °C/65 % RH for 6 months. Overall, these findings contribute to advancing stent technology, suggesting the potential for improvement of arterial interventions and enhanced patient outcomes.

Inhaled tea polyphenol-loaded nanoparticles coated with platelet membranes largely attenuate asthmatic inflammation

BackgroundTea polyphenols (TPs), prominent constituents of green tea, possess remarkable antioxidant and anti-inflammatory properties. However, their therapeutic potential is limited due to low absorption and poor bioavailability. To address this limitation and enhance their efficacy, we developed a biomimetic nanoplatform by coating platelet membrane (PM) onto poly-lactic-co-glycolic acid (PLGA) nanoparticles (NPs) to create targeted delivery vehicles for TPs (PM@TP/NPs) to the inflamed tissues in asthma.MethodsAfter synthesizing and characterizing PM@TP/NPs, we assessed their biocompatibility and biosafety through cell viability assays, hemolysis tests, and inflammation analysis in vivo and in vitro. The therapeutic effect of PM@TP/NPs on asthma was then evaluated using a mouse model of HDM-induced asthma. Additionally, PM@TP/NPs-mediated reactive oxygen species (ROS) scavenging capacity, as well as the activation of signaling pathways, were analyzed in HBE cells and asthmatic mice via flow cytometry, RT-qPCR, and western blotting.ResultsCompared with free TPs, PM@TP/NPs demonstrated excellent biocompatibility and safety profiles in both in vitro and in vivo, as well as enhanced retention in inflamed lungs. In HDM-induced mouse asthma model, inhaled PM@TP/NPs largely attenuated lung inflammation and reduced the secretion of type 2 pro-inflammatory cytokines in the lungs compared to free TPs. The therapeutic effects of PM@TP/NPs on asthma might be associated with an enhanced ROS scavenging capacity, increased activation of the Nrf2/HO-1 pathway, and decreased activation of the CCL2/MAPK and TLR4/NF-κB pathway in the lungs.ConclusionsOur findings demonstrate that inhalation of PM@TP/NPs largely attenuated lung inflammation in HDM-induced asthmatic mice. These results suggest that PM@TP/NPs might be a novel therapeutic strategy for asthma.

Enhancing neurite growth and neural functions on polymeric nerve conduit with BMSC-derived ECM coating

The therapy of large defects in peripheral nerve injury (PNI) suffers from several drawbacks, especially the lack of autologous nerve donors. Nerve conduits are considered as a solution for nerve injury treatment, but biocompatibility improvements is still required for conduits prepared with synthetic materials. Cell-derived extracellular matrix (ECM) has drawn attention due to its lower risk of immunogenic response and independence from donor availability. The goal of this study is to coat bone mesenchymal stem cell-derived ECMs on poly(lactic-co-glycolic) acid (PLGA) conduits to enhance their ability to support neural growth and neurite extensions. The ECM-coated conduits have better hydrophilic properties than the pure PLGA conduits. A marked increase on PC12 and RSC96 cells' viability, proliferation and dorsal root ganglion neurite extension was observed. Quantitative PCR analysis exhibited a significant increase in markers for cell proliferation (GAP43), neurite extension (NF-H, MAP2, andβIII-tubulin) and neural function (TREK-1). These results show the potential of ECM-coated PLGA conduits in PNI therapy.

Development of modular polymeric nanoparticles for drug delivery using amine reactive chemistry.

Curcumin has been explored for its anti-cancer potential, but is severely limited by its hydrophobicity and sensitivity to light and water. In this study, poly (lactic-co-glycolic) acid (PLGA) nanoparticles (NPs) were synthesized to encapsulate curcumin via single emulsion method to improve curcumin stability and bioavailability. The PLGA NPs were coated with oligomeric chitosan (COS) and RGD peptide (a peptide consisting of Arg-Gly-Asp) using amine-reactive chemistry (NHS and EDC). Both COS and RGD had been previously shown to accumulate and target many different types of cancer cells. NPs were characterised based on size distribution, zeta potential, and binding efficiency of RGD peptide. They were also evaluated on encapsulation efficiency, and stability, of curcumin within the NPs. OVCAR-3 cancer cells were treated with COS and RGD-coated PLGA NPs loaded with Coumarin-6 dye for fluorescent imaging of cell uptake. They were also treated with curcumin-loaded NPs to determine cytotoxicity and effectiveness of delivery. The NPs exhibited size distribution and zeta potential within expected values, though binding efficiency of RGD was low. Curcumin-loaded NPs showed significant increase in cytotoxicity over free (unencapsulated) curcumin, and void (empty) NPs, suggesting successful delivery of curcumin as an anti-cancer agent; the performance of COS and RGD coated NPs over bare PLGA NPs was inconclusive, however, optimization will be required to improve formulation during the coating steps. This method of NP synthesis serves as proof of concept for a modular solution to the development of various coated polymeric NPs for other drugs or applications.

Infection-Sensitive SPION/PLGA Scaffolds Promote Periodontal Regeneration via Antibacterial Activity and Macrophage-Phenotype Modulation.

Inflammation caused by a bacterial infection and the subsequent dysregulation of the host immune-inflammatory response are detrimental to periodontal regeneration. Herein, we present an infection-sensitive scaffold prepared by layer-by-layer assembly of Feraheme-like superparamagnetic iron oxide nanoparticles (SPIONs) on the surface of a three-dimensional-printed polylactic-co-glycolic acid (PLGA) scaffold. The SPION/PLGA scaffold is magnetic, hydrophilic, and bacterial-adhesion resistant. As indicated by gene expression profiling and confirmed by quantitative real-time reverse transcription polymerase chain reaction and flow cytometry analysis, the SPION/PLGA scaffold facilitates macrophage polarization toward the regenerative M2 phenotype by upregulating IL-10, which is the molecular target of repair promotion, and inhibits macrophage polarization toward the proinflammatory M1 phenotype by downregulating NLRP3, which is the molecular target of anti-inflammation. As a result, macrophages modulated by the SPS promote osteogenic differentiation of bone marrow mesenchymal stromal cells (BMSCs) in vitro. In a rat periodontal defect model, the SPION/PLGA scaffold increased IL-10 secretion and decreased NLRP3 and IL-1β secretion with Porphyromonas gingivalis infection, achieving superior periodontal regeneration than the PLGA scaffold alone. Therefore, this antibacterial SPION/PLGA scaffold has anti-inflammatory and bacterial antiadhesion properties to fight infection and promote periodontal regeneration by immunomodulation. These findings provide an important strategy for developing engineered scaffolds to treat periodontal defects.

Measuring Erosion of Biodegradable Polymers in Brimonidine Drug Delivery Implants by Quantitative Proton NMR Spectroscopy (q-HNMR)

Erosion of biodegradable polymeric excipients, such as polylactic acid (PLA) and polylactic-co-glycolic acid (PLGA), is generally characterized by microbalance for the remaining mass of PLA and/or PLGA and Gel Permeation Chromatography (GPC) for molecular weight (MW) decrease. For polymer erosion studies of intravitreal sustained release brimonidine implants, however, both microbalance and GPC present several challenges. Mass loss measurement by microbalance does not have specificity for excipient polymers and drug substances. Accuracy of the remaining mass by weighing could also be low due to sample mass loss through retrieval-drying steps, especially at later drug release (DR) time points. When measuring the decrease of polymer MW by GPC, trace amounts of polymeric degradants (oligomers and/or monomers) trapped inside the implants during DR tests may not be measurable due to sensitivity limitations of the GPC detector and column MW range. Previous efforts to measure remained PLGA weight of dexamethasone micro-implants using qNMR with external calibration have been performed, however, these measurements do not account for chemical structure changes (i.e. LA to GA ratio changes from time zero) of PLGA implants during drug release tests. Here, a qNMR method with an internal standard was developed to monitor the following changes in micro-implants during drug release tests: 1. The remaining overall PLA/PLGA mass. 2. The remaining lactic acid (LA), glycolic acid (GA) unit and PLGA's lauryl ester end group percentages. 3. The trace content of PLA/PLGA oligomers as degradants retained in the implants. Unlike microbalance analysis, qNMR has both specificity for drug substance, excipient polymer, and accuracy due to minimal implant loss during sample preparation. Compared to the overall PLA/PLGA remaining mass generally monitored in erosion studies, the percentage of remaining LA, GA, and the ester end group provide more information about the microstructure change (such as hydrophobicity) of PLA/PLGA. Additionally, the qNMR method can complement GPC methods by measuring the change of remaining PLA and PLGA oligomer concentrations in brimonidine implants, with tenfold less sample and no MW cutoff. The qNMR method can be used as a sensitive tool for both polymer excipient characterization and kinetics studies of brimonidine implant erosion.

Measurements of Spontaneous and External Stimuli Molecular Release Processes from a Single Optically Trapped Poly(lactic-co-glycolic) Acid Microparticle and a Liposome Containing Gold Nanospheres.

We investigated the single particle kinetics of the molecular release processes from two types of microcapsules used as drug delivery systems (DDS): biodegradable poly(lactic-co-glycolic) acid (PLGA) and a light-triggered-degradable liposome encapsulating gold nanospheres (liposome-GNP). To optimize the design of DDS capsules, it is highly desirable to develop a method for real-time monitoring of the release process. Using a combination of optical tweezers and confocal fluorescence microspectroscopy we successfully analyzed a single optically trapped PLGA particle and liposome-GNPs in solution. From temporal decay profiles of the fluorescence intensity, we determined the time constant τ of the release processes. We demonstrated that the release rate of spontaneously degradable microcapsules (PLGA) decreased with increasing size, while conversely, the release rate of external stimuli-degradable microcapsules (liposome-GNPs) increased in proportion to their size. This result is explained by the differences in the disruption mechanisms of the capsules, with PLGA undergoing hydrolysis and the GNPs in the liposome-GNP undergoing a photoacoustic effect under nanosecond pulsed laser irradiation. The present approach offers a way forward to an alternative microanalysis system for single drug delivery nanocarriers.

Hydrophilic phycocyanin encapsulation in PLGA nanoparticles using benchtop microfluidic device

Phycocyanin (PC), a sensitive hydrophilic protein with significant biological functions, is prone to denaturation in harsh environmental conditions. Here, we employ a microfluidic-assisted nanoprecipitation approach using poly lactic-co-glycolic acid (PLGA) as a protective coating material to shield PC from such conditions. Despite the complexity of microfluidic device preparation and the challenge of encapsulating water-like protein with high association efficiency, our study demonstrates the successful generation of nanosized PC-loaded particles using a 1-mm-width microfluidic device. Optimal device parameters, including a 90˚ intersecting angle, a 3-cm-length outlet channel, and a total flow rate of 396 µLmin−1, yielded particles approximately 200 nm in size with an association efficiency (AE) of around 80 %. Notably, DMSO proved to be an effective organic solvent for preserving PC. Interestingly, surfactants typically employed for stability and biocompatibility in microfluidic techniques, were found to be unnecessary in this system, potentially altering the secondary structure of PC, as indicated by circular dichroism (CD) spectra. Overall, this research confirms the feasibility of producing nanosized particles with monodisperse spherical morphology using a benchtop microfluidic device. Moreover, the enhanced association efficiency of hydrophilic protein in PLGA holds significant promise for encapsulating non-hydrophobic proteins.

Toxicological Analysis of Nanoparticles and Microparticles Used as Oral Vaccine Delivery Systems using Vero Cell

Background: The present study was carried out to evaluate in-vitro toxicity associated with chitosan nanoparticles, Gantrez® nanoparticles and poly-lactide co-glycolide (PLG) microparticle in Vero cell line. The cytotoxicity of all three micro/nano-particles was assessed using different concentration. Methods: For each concentration of these delivery systems, the confluent monolayer of Vero cells was treated for a period of 48 hours and studied for morphological alteration and cell survivability after the treatment. Results: It was observed that the different concentrations of chitosan nanoparticles and Gantrez® nanoparticles did not have significant effect on the cell viability as evident from the non-significant difference between the OD540 of formazan product formed from MTT in treated and untreated cells. The concentration of chitosan nanoparticles and Gantrez® nanoparticles up to 1000 µg/ml did not have any influence in cellular metabolic activities and viability. However, a slight reduction (statistically insignificant) in the cellular viability and metabolic activities were observed when PLG microparticles were used at 1000 µg/ml.

Novel Delivery Systems for Oral Administration of Enfuvirtide: New Treatment Options for HIV/AIDS

AbstractEnfuvirtide (T‐20) is a synthetic peptide fusion inhibitor for the human immunodeficiency virus (HIV), which causes acquired immunodeficiency syndrome (AIDS). However, the peptide nature limits a wider application of T‐20 with subcutaneous injection (Fuzeon) the only available formulation. In this groundbreaking study, it is sought to overcome this limitation by employing poly lactic‐co‐glycolic acid (PLGA) and alginate to create novel oral delivery systems for T‐20. Remarkably, this investigation marks the first instance of assessing the efficacy of oral delivery systems in mice. Notably, both the PLGA and alginate formulations exhibit the capability to sustain T‐20 release, maintaining detectable levels in the bloodstream of mice for over 24 h after a single dose. By venturing into the realm of oral T‐20 delivery, this study opens avenues for the prospective development of oral formulations of T‐20, potentially leading to their evaluation in clinical trials.

Poly Lactic-co-Glycolic Acid (PLGA) Loaded with a Squaraine Dye as Photosensitizer for Antimicrobial Photodynamic Therapy.

Antimicrobial Photodynamic Therapy (aPDT) is an innovative and promising method for combating infections, reducing the risk of antimicrobial resistance compared to traditional antibiotics. Squaraine (SQ) dyes can be considered promising photosensitizers (PSs) but are generally hydrophobic molecules that can self-aggregate under physiological conditions. To overcome these drawbacks, a possible solution is to incorporate SQs inside nanoparticles (NPs). The present work deals with the design and development of innovative nanophotosensitizers based on poly lactic-co-glycolic acid (PLGA) NPs incorporating a brominated squaraine (BrSQ) with potential application in aPDT. Two designs of experiments (DoEs) based on the single emulsion and nanoprecipitation methods were set up to investigate how different variables (type of solvent, solvent ratio, concentration of PLGA, stabilizer and dye, sonication power and time) can affect the size, zeta (ζ)-potential, yield, entrapment efficiency, and drug loading capacity of the SQ-PLGA NPs. SQ-PLGA NPs were characterized by NTA, FE-SEM, and UV-Vis spectroscopy and the ability to produce reactive oxygen species (ROS) was evaluated, proving that ROS generation ability is preserved in SQ-PLGA. In vitro antimicrobial activity against Gram-positive bacteria in planktonic state using Staphylococcus aureus was conducted in different conditions and pH to evaluate the potential of these nanophotosensitizers for aPDT in the local treatment of infections.

Erythrocyte membrane biomimetic EGCG nanoparticles attenuate renal injury induced by diquat through the NF-κB/NLRP3 inflammasome pathway.

Diquat (DQ) poisoning can cause multiple organ damage, and the kidney is considered to be the main target organ. Increasing evidence shows that alleviating oxidative stress and inflammatory response has promising application prospects. Epigallocatechin gallate (EGCG) has potent antioxidant and anti-inflammatory effects. In this study, red blood cell membrane (RBCm)-camouflaged polylactic-co-glycolic acid (PLGA) nanoparticles (NPs) were synthesized to deliver EGCG (EGCG-RBCm/NPs) for renal injury induced by DQ. Human renal tubular epithelial cells (HK-2 cells) were stimulated with 600μM DQ for 12h and mice were intraperitoneally injected with 50mg/kg b.w. DQ, followed by 20mg/kg b.w./day EGCG or EGCG-RBCM/NPs for 3days. The assessment of cellular vitality was carried out using the CCK-8 assay, while the quantification of reactive oxygen species (ROS) was performed through ROS specific probes. Apoptosis analysis was conducted by both flow cytometry and TUNEL staining methods. Pathological changes in renal tissue were observed. The expressions of NLRP3, IL-1β, IL-18, NFκB and Caspase1 were detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR), immunohistochemistry, immunofluorescence, and Western blot. The results showed that the DQ group had increased ROS expression, increased the level of oxidative stress, and increased apoptosis rate compared with the control group. Histopathological analysis of mice in the DQ group showed renal tubular injury and elevated levels of blood urea nitrogen (BUN), serum creatinine (SCr), kidney injury molecule-1 (KIM-1), and cystatin C (Cys C). Furthermore, the DQ group exhibited heightened expression of NLRP3, p-NFκB p65, Caspase1 p20, IL-1β, and IL-18. However, EGCG-RBCm/NPs treatment mitigated DQ-induced increases in ROS, apoptosis, and oxidative stress, as well as renal toxicity and decreases in renal biomarker levels. Meanwhile, the expression of the above proteins were significantly decreased, and the survival rate of mice was ultimately improved, with an effect better than that of the EGCG treatment group. In conclusion, EGCG-RBCm/NPs can improve oxidative stress, inflammation, and apoptosis induced by DQ. This effect is related to the NF-κB/NLRP3 inflammasome pathway. Overall, this study provides a new approach for treating renal injury induced by DQ.

Designing and developing a programmable in vitro gastrointestinal model to assess the impact of pasteurization on the bioaccessibility of lycopene nanoparticles

To evaluate potential health impact of engineered nanoparticles, evaluation of digestion effect is necessary. Digestion requires micro-management and sequential execution of complex enzymatic mechanisms with controlled human digestion environment. The objective of this study was to develop an automated in-vitro digestive system to assess bio-accessibility of encapsulated lycopene nanoparticles in model fruit juice. Lycopene was encapsulated in polylactic acid (PLA-LNP) and polylactic co-glycolic acid (PLGA-LNP) and evaluated the bio-accessibility in a programmable in-vitro human digestive system operated with high sensitivity (25–30μs) and volume accuracy (97.37–100%). Pasteurized Model juice containing PLA-LNP, revealing higher bio-accessibility (100%) compared to PLGA-LNP (73%) counterparts. Absorption profile of both types of nanoparticles followed Korsmeyer-Peppas diffusion model at R2 value of 0.98. All types of nanoparticles with different treatments followed non-Fickian types of diffusion except PLGA-PLA with microwave pasteurization. This automated in-vitro digestive system holds significant potential for advancing drug discovery and delivery studies in the future.

Exploring Disulfiram's Anticancer Potential: PLGA Nano-Carriers for Prolonged Drug Delivery and Potential Improved Therapeutic Efficacy.

Disulfiram (DS) has been shown to have potent anti-cancer activity; however, it is also characterised by its low water solubility and rapid metabolism in vivo. Biodegradable polylactic-co-glycolic acid (PLGA) polymers have been frequently employed in the manufacturing of PLGA nano-carrier drug delivery systems. Thus, to develop DS-loaded PLGA nanoparticles (NPs) capable of overcoming DS's limitations, two methodologies were used to formulate the NPs: direct nanoprecipitation (DNP) and single emulsion/solvent evaporation (SE), followed by particle size reduction. The DNP method was demonstrated to produce NPs of superior characteristics in terms of size (151.3 nm), PDI (0.083), charge (-37.9 mV), and loading efficiency (65.3%). Consequently, NPs consisting of PLGA and encapsulated DS coated with mPEG2k-PLGA at adjustable ratios were prepared using the DNP method. Formulations were then characterised, and their stability in horse serum was assessed. Results revealed the PEGylated DS-loaded PLGA nano-carriers to be more efficient; hence, in-vitro studies testing these formulations were subsequently performed using two distinct breast cancer cell lines, showing great potential to significantly enhance cancer therapy.

Oral administration of recombinant outer membrane protein A-based nanovaccine affords protection against Aeromonas hydrophila in zebrafish.

Aeromonas hydrophila, an opportunistic warm water pathogen, has always been a threat to aquaculture, leading to substantial economic losses. Vaccination of the cultured fish would effectively prevent Aeromoniasis, and recent advancements in nanotechnology show promise for efficacious vaccines. Oral delivery would be the most practical and convenient method of vaccine delivery in a grow-out pond. This study studied the immunogenicity and protective efficacy of a nanoparticle-loaded outer membrane protein A from A. hydrophila in the zebrafish model. The protein was over-expressed, purified, and encapsulated using poly lactic-co-glycolic acid (PLGA)nanoparticles via the double emulsion method. The PLGA nanoparticles loaded with recombinant OmpA (rOmpA) exhibited a size of 295 ± 15.1nm, an encapsulation efficiency of 72.52%, and a polydispersity index of 0.292 ± 0.07. Scanning electron microscopy confirmed the spherical and isolated nature of the PLGA-rOmpA nanoparticles. The protective efficacy in A. hydrophila-infected zebrafish after oral administration of the nanovaccine resulted in relative percentage survival of 77.7. Gene expression studies showed significant upregulation of immune genes in the vaccinated fish. The results demonstrate the usefulness of oral administration of nanovaccine-loaded rOmpA as a potential vaccine since it induced a robust immune response and conferred adequate protection against A. hydrophila in zebrafish, Danio rerio.

Platelet Membrane-Coated Curcumin-PLGA Nanoparticles Promote Astrocyte-Neuron Transdifferentiation for Intracerebral Hemorrhage Treatment.

Intracerebral hemorrhage (ICH) is a hemorrhagic disease with high mortality and disability rates. Curcumin is a promising drug for ICH treatment due to its multiple biological activities, but its application is limited by its poor watersolubility and instability. Herein, platelet membrane-coated curcumin polylactic-co-glycolic acid (PLGA) nanoparticles (PCNPs) are prepared to achieve significantly improved solubility, stability, and sustained release of curcumin. Fourier transform infrared spectra and X-ray diffraction assays indicate good encapsulation of curcumin within nanoparticles. Moreover, it is revealed for the first time that curcumin-loaded nanoparticles can not only suppress hemin-induced astrocyte proliferation but also induce astrocytes into neuron-like cells in vitro. PCNPs are used to treat rat ICH by tail vein injection, using in situ administration as control. The results show that PCNPs are more effective than curcumin-PLGA nanoparticles in concentrating on hemorrhagic lesions, inhibiting inflammation, suppressing astrogliosis, promoting neurogenesis, and improving motor functions. The treatment efficacy of intravenously administered PCNPs is comparable to that of in situ administration, indicating a good targeting effect of PCNPs on the hemorrhage site. This study provides a potent treatment for hemorrhagic injuries and a promising solution for efficient delivery of water-insoluble drugs using composite materials of macromolecules and cell membranes.

USP’s characterization of commercial poly(lactic-co-glycolic acid) utilizing SEC-Multi-Angle Light Scattering and Refractive Index techniques via Absolute Method approach

This research focuses on evaluating the data quality and reliability of Size Exclusion Chromatography with Multi-Angle Light Scattering and Refractive Index (SEC-MALS/RI) chromatography in determining molecular weight-related parameters in poly(lactic-co-glycolic) acid (PLGA) polymers. The study utilizes key metrics, particularly percent relative standard deviation (%RSD), to evaluate the precision across different data processing conditions. Exploring baseline selection of the chromatograms reveals that selection of the baseline based on the intrinsic shape of the chromatogram, rather than relying on elution peaks, improves consistency. The study emphasizes the critical role of result fitting in addressing systematic errors and sample heterogeneity, recommending the minima of the elution peak selection range for realistic molecular weight distribution representation. Analysis of light-scattering (LS) detector chromatograms highlights varying effects on different PLGA polymers, emphasizing the need for careful assessment and potential exclusion for precision improvement, especially in the presence of experimental artifacts. Across diverse PLGA polymers, the utilization of different column types, along with considerations such as baseline determination and peak selection, shows minimal variations in Mn, Mw, and polydispersity index (PDI), affirming the consistency of the methodology. The %RSD analysis further supports the methodology's precision, with values well within acceptable limits. In summary, this comprehensive evaluation of methodological conditions, including baseline selection, result fitting, LS detector data management, and column types, establishes a reliable SEC-MALS/RI chromatographic approach by Absolute Method for determining molecular weight parameters in PLGA polymers.