Osteogenic effect of poly(lactic-co-glycolic acid) microcapsules with different molecular weights encapsulating bone morphogenetic protein 2.

OBJECTIVES: This study aimed to explore the effects of bone morphogenetic protein 2 (BMP-2) encapsula-ted in poly(lactic-co-glycolic acid) (PLGA) microcapsules with different molecular weights on the osteogenic ability of osteoblasts. METHODS: PLGA microcapsules with different molecular weights (12 000, 30 000) encapsulating BMP-2, were prepared using a dual-channel microinjection pump. The morphology and structure of the microcapsules were characterized by optical microscopy and scanning electron microscopy. The sustained-release performance of the microcapsules was characterized by phosphate buffered saline immersion method. The cell compatibility of the microcapsules was detected by the Calcein-AM/PI staining and CCK-8 method. The chemotactic effect of BMP-2-encapsulated microcapsules on MC3T3-E1 cells after 48 h of treatment was detected by the Transwell assay. The alkaline phosphatase activity assay and Alizarin Red S staining were used to characterize the effect of microcapsules on the osteogenic ability of MC3T3-E1 cells. RESULTS: Both types of microcapsules with different molecular weights exhibited smooth surfaces, as well as uniform and good cell compatibility. The chemotactic effect of the 12 000 microcapsules was outstanding. The 30 000 microcapsules had a longer sustained-release time, and the initial burst release was reduced by approximately 25% compared with the 12 000 microcapsules. In addition, 30 000 microcapsules performed better in long-term osteogenesis induction than 12 000 microcapsules. CONCLUSIONS: In this study, the release of BMP-2 is regulated by adjusting the molecular weight of PLGA, and the results indicate that 30 000 microcapsules can better induce the long-term osteogenic ability of MC3T3-E1 cells.

PLGA Nanoparticles Based Mucoadhesive Nasal In Situ Gel for Enhanced Brain Delivery of Topiramate.

Oral Topiramate therapy is associated with systemic adverse effects including paresthesia,abdominal pain, and fluctuations in plasma levels. The purpose of this research was to develop an intranasal in situ gel based system comprising Topiramate polymeric nanoparticles and evaluate its potential both in vitro and in vivo. Poly (lactic-co-glycolic acid) (PLGA)nanoparticles prepared by nanoprecipitation method were added into the in situ gelling system of Poloxamer 407 and HPMC K4M. Selected formulation (TG5) was evaluated for physicochemical properties, nasal permeation and in vivo pharmacokinetics in rats. PLGAnanoparticles (O1) exhibited low particle size (~ 144.4 nm), good polydispersity index (0.202), negative zeta potential (-12.7 mV), and adequate entrapment efficiency (64.7%). Developed in situ gel showed ideal pH (6.5), good gelling time (35 s), gelling temperature(37℃), suitable viscosity (1335 cP)and drug content of 96.2%. In vitro drug release conformedto Higuchi release kinetics, exhibiting a biphasic pattern of initial burst release and sustained release for 24 h. Oral administration of the drug to Sprague-Dawley rats (G3) showed higher plasma Cmax(504 ng/ml, p < 0.0001) when compared to nasal delivery of in situ gel (G4) or solution (G5). Additionally, AUC0-α of G3 (8786.82 ng/ml*h) was considerably higher than othergroups. Brain uptake data indicates a higher drug level with G4 (112.47 ng /ml) at 12 h when compared to G3. Histopathological examination of groups; G1 (intranasal saline), G2(intranasal placebo), G3, G4, and G5 did not show any lesions of pathological significance. Overall, the experimental results observed were promising and substantiated the potential of developed in situ gel for intranasal delivery.

The efficiency of two different synthetic bone graft materials on alveolar ridge preservation after tooth extraction: a split-mouth study.

BACKGROUND: Alveolar Bone loss occurs frequently during the first six months after tooth extraction. Various studies have proposed different methods to reduce as much as possible the atrophy of the alveolar ridge after tooth extraction. Filling the socket with biomaterials after extraction can reduce the resorption of the alveolar ridge. We compared the height of the alveolar process at the mesial and distal aspects of the extraction site and the resorption rate was calculated after the application of HA/ß-TCP or synthetic co-polymer polyglycolic - polylactic acid PLGA mixed with blood to prevent socket resorption immediately and after tooth extraction. METHODS: The study was conducted on 24 extraction sockets of impacted mandibular third molars bilaterally, vertically, and completely covered, with a thin bony layer. HA/ß-TCP was inserted into 12 of the dental sockets immediately after extraction, and the synthetic polymer PLGA was inserted into 12 of the dental sockets. All sockets were covered completely with a full-thickness envelope flap. Follow-up was performed for one year after extraction, using radiographs and stents for the vertical alveolar ridge measurements. RESULTS: The mean resorption rate in the HA/ß-TCP and PLGA groups was ± 1.23 mm and ± 0.1 mm, respectively. A minimal alveolar bone height reduction of HA/ß-TCP was observed after 9 months, the reduction showed a slight decrease to 0.93 mm, while this rate was 0.04 mm after 9 months in the PLGA group. Moreover, the bone height was maintained after three months, indicating a good HA/ß-TCP graft performance in preserving alveolar bone (1.04 mm) while this rate was (0.04 mm) for PLGA. CONCLUSION: The PLGA graft demonstrated adequate safety and efficacy in dental socket preservation following tooth extraction. However, HA/ß-TCP causes greater resorption at augmented sites than PLGA, which clinicians should consider during treatment planning.

Swarms of Enzymatic Nanobots for Efficient Gene Delivery.

This study investigates the synthesis and optimization of nanobots (NBs) loaded with pDNA using the layer-by-layer (LBL) method and explores the impact of their collective motion on the transfection efficiency. NBs consist of biocompatible and biodegradable poly(lactic-co-glycolic acid) (PLGA) nanoparticles and are powered by the urease enzyme, enabling autonomous movement and collective swarming behavior. In vitro experiments were conducted to validate the delivery efficiency of fluorescently labeled NBs, using two-dimensional (2D) and three-dimensional (3D) cell models: murine urothelial carcinoma cell line (MB49) and spheroids from human urothelial bladder cancer cells (RT4). Swarms of pDNA-loaded NBs showed enhancements of 2.2- to 2.6-fold in delivery efficiency and 6.8- to 8.1-fold in material delivered compared to inhibited particles (inhibited enzyme) and the absence of fuel in a 2D cell culture. Additionally, efficient intracellular delivery of pDNA was demonstrated in both cell models by quantifying and visualizing the expression of eGFP. Swarms of NBs exhibited a >5-fold enhancement in transfection efficiency compared to the absence of fuel in a 2D culture, even surpassing the Lipofectamine 3000 commercial transfection agent (cationic lipid-mediated transfection). Swarms also demonstrated up to a 3.2-fold enhancement in the amount of material delivered in 3D spheroids compared to the absence of fuel. The successful transfection of 2D and 3D cell cultures using swarms of LBL PLGA NBs holds great potential for nucleic acid delivery in the context of bladder treatments.

Adapting to the acidic environment of the NP: RADA16-PLGA (TGF-ß3) induces chondrogenic differentiation of BMSCs.

Aim: RADA16-PLGA composite scaffolds constructed with simultaneous loading of BMSCs and TGF-ß3 and explored their ability for chondrogenic differentiation in vitro.Methods: The performance of the composite scaffolds is assessed by rheometer assay, electron microscopic structural observation and ELISA release assay. The biosafety of the composite scaffolds is assessed by cytocompatibility assay and cell migration ability. The chondrogenic differentiation ability of composite scaffolds is evaluated by Alisin blue staining, PCR and immunofluorescence staining.Results: The composite scaffold has a good ECM-like structure, the ability to control the release of TGF-ß3 and good biocompatibility. More importantly, the composite scaffolds can induce the differentiation of BMSCs to chondrocytes.Conclusion: Composite scaffolds are expected to enhance the endogenous NP repair process.

[Box: see text].

Arg-Specific serine Protease-Targeted edoxaban tosylate monohydrate-Poly (lactic-co-glycolic acid) Nanoparticles: Investigating Stuart-Prower factor targeting and intestinal distribution through Ex-Vivo fluorescent visualization.

The goal of the current study was to formulate and examine the potential of poly (lactic-co-glycolic acid) (PLGA) as carriers to facilitate the targeted administration of edoxaban tosylate monohydrate (ETM). ETM-PLGA-NPs were effectively formulated using the nanoprecipitation technique. Particle size, drug entrapment percentage, zeta potential, assessment of intestinal absorption, FT-IR, SEM, drug dissolution behavior, and histopathology investigations were used to describe ETM-PLGA-NPs. The produced NPs had a roughly spherical shape with a particle size of 99.85 d.nm, a PDI of 0.478, and a zeta potential of 38.5 mV with a maximum drug entrapment of 82.1 %. FTIR measurements showed that the drug's chemical stability remained intact after preapred into nanoparticles. In vitro drug release behavior followed the Higuchi model and revealed an early burst release of 30 % and persistent drug release of 78 % from optimized NPs for up to 120 hrs. According to in vitro data, a 1:10 ratio of ETM to PLGA provided longer-lasting ETM release and improved encapsulation efficiency. Images captured with an inverted fluorescent microscope exhibited that NPs may both greatly increase the amount of ETM accumulated in the intestinal tract and make it easier for ETM to enter the membrane beneath the cells of the intestines. The study found that using PLGA nanoparticles to encapsulate the ETM resulted in longer circulation duration (aPTT, PT, TT). In vivo investigations found that nanoparticles encapsulated had no negative impact on hematological parameters, lung, liver, or kidney tissues. All things considered, the NPs are a potential delivery method to increase the oral absorption and antithrombotic activity of ETM.

Design and simulation of scaffolds with lattice microstructures for bioprinting bone tissue.

BACKGROUND: Tissue engineering seeks to improve, maintain, or replace the biological functions of damaged organs or tissues with biological substitutes such as the development of scaffolds. In the case of bone tissue, they must have excellent mechanical properties like native bone. OBJECTIVE: In this work, three geometric models were designed for scaffolds with different structure lattices and porosity that could be biomechanically suitable and support cell growth for trabecular bone replacement applications in tissue engineering and regenerative medicine to the proximal femur area. METHODS: Geometries were designed using computer-aided design (CAD) software and evaluated using finite element analysis in compression tests. Three loads were considered according to the daily activity: 1177 N for slow walking, 2060 N for fast walking, and 245.25 N for a person in a bipedal position. All these loads for an adult weight of 75 kg. For each of them, three biomaterials were assigned: two polymers (poly-glycolic acid (PGA) and poly-lactic acid (PLA)) and one mineral (hydroxyapatite (HA)). 54 tests were performed: 27 for each of the tests. RESULTS: The results showed Young's modulus (E) between 1 and 4 GPa. CONCLUSION: If the resultant E is in the range of 0.1 to 5 GPa, the biomaterial is considered an appropriate alternative for the trabecular bone which is the main component of the proximal bone. However, for the models applied in this study, the best option is the poly-lactic acid which will allow absorbing the acting loads.

Evaluation of the release kinetics of hydrophilic and lipophilic compounds from lipid-polymer hybrid nanoparticles.

In disease treatment, maintaining therapeutic drug concentrations often requires multiple doses. Lipid/polymer hybrid nanoparticles (LPHNPs) offer a promising solution by facilitating sustained drug delivery within therapeutic ranges. Here, we synthesized poly(lactic-co-glycolic acid) (PLGA) nanoparticles coated with soy lecithin using nanoprecipitation and self-assembly techniques. These nanoparticles were incorporated into gelatin aerogels to ensure uniform distribution and increase the concentration. Our study focused on understanding the release kinetics of hydrophilic (gallic acid) and lipophilic (quercetin) compounds from this system. Nanoparticles exhibited hydrodynamic diameters of 100 ± 15 nm (empty), 153 ± 33 nm (gallic acid-loaded), and 149 ± 21 nm (quercetin-loaded), with encapsulation efficiencies of 90 ± 5% and 70 ± 10% respectively. Gallic acid release followed the Korsmeyer-Peppas kinetics model (n = 1.01), while quercetin showed first-order kinetics. Notably, encapsulated compounds demonstrated delayed release compared to free compounds in gelatin aerogels, illustrating LPHNPs' ability to modulate release profiles independent of the compound type. This study underscores the potential of LPHNPs in optimizing drug delivery strategies for enhanced therapeutic outcomes.

In vitro evaluation of PLGA loaded hesperidin on colorectal cancer cell lines: an insight into nano delivery system.

BACKGROUND: Colorectal cancer is a common disease worldwide with non-specific symptoms such as blood in the stool, bowel movements, weight loss and fatigue. Chemotherapy drugs can cause side effects such as nausea, vomiting and a weakened immune system. The use of antioxidants such as hesperidin could reduce the side effects, but its low bioavailability is a major problem. In this research, we aimed to explore the drug delivery and efficiency of this antioxidant on the HCT116 colorectal cancer cell line by loading hesperidin into PLGA nanoparticles. MATERIALS AND METHODS: Hesperidin loaded PLGA nanoparticles were produced by single emulsion evaporation method. The physicochemical properties of the synthesized hesperidin-loaded nanoparticles were determined using SEM, AFM, FT-IR, DLS and UV-Vis. Subsequently, the effect of the PLGA loaded hesperidin nanoparticles on the HCT116 cell line after 48 h was investigated by MTT assay at three different concentrations of the nanoparticles. RESULT: The study showed that 90% of hesperidin were loaded in PLGA nanoparticles by UV-Vis spectrophotometry and FT-IR spectrum. The nanoparticles were found to be spherical and uniform with a hydrodynamic diameter of 76.2 nm in water. The release rate of the drug was about 93% after 144 h. The lowest percentage of cell viability of cancer cells was observed at a concentration of 10 µg/ml of PLGA nanoparticles loaded with hesperidin. CONCLUSION: The results indicate that PLGA nanoparticles loaded with hesperidin effectively reduce the survival rate of HCT116 colorectal cancer cells. However, further studies are needed to determine the appropriate therapeutic dosage and to conduct animal and clinical studies.

Development of poly (lactic-co-glycolic acid) (PLGA) based implants using hot melt extrusion (HME) for sustained release of drugs: The impacts of PLGA's material characteristics.

Hot melt extrusion (HME) processed Poly (lactic-co-glycolic acid) (PLGA) implant is one of the commercialized drug delivery products, which has solid, well-designed shape and rigid structures that afford efficient locoregional drug delivery on the spot of interest for months. In general, there are a variety of material, processing, and physiological factors that impact the degradation rates of PLGA-based implants and concurrent drug release kinetics. The objective of this study was to investigate the impacts of PLGA's material characteristics on PLGA degradation and subsequent drug release behavior from the implants. Three model drugs (Dexamethasone, Carbamazepine, and Metformin hydrochloride) with different water solubility and property were formulated with different grades of PLGAs possessing distinct co-polymer ratios, molecular weights, end groups, and levels of residual monomer (high/ViatelTM and low/ ViatelTM Ultrapure). Physicochemical characterizations revealed that the plasticity of PLGA was inversely proportional to its molecular weight; moreover, the residual monomer could impose a plasticizing effect on PLGA, which increased its thermal plasticity and enhanced its thermal processability. Although the morphology and microstructure of the implants were affected by many factors, such as processing parameters, polymer and drug particle size and distribution, polymer properties and polymer-drug interactions, implants prepared with ViatelTM PLGA showed a smoother surface and a stronger PLGA-drug intimacy than the implants with ViatelTM Ultrapure PLGA, due to the higher plasticity of the ViatelTM PLGA. Subsequently, the implants with ViatelTM PLGA exhibited less burst release than implants with ViatelTM Ultrapure PLGA, however, their onset and progress of the lag and substantial release phases were shorter and faster than the ViatelTM Ultrapure PLGA-based implants, owing to the residual monomer accelerated the water diffusion and autocatalyzed PLGA hydrolysis. Even though the drug release profiles were also influenced by other factors, such as composition, drug properties and polymer-drug interaction, all three cases revealed that the residual monomer accelerated the swelling and degradation of PLGA and impaired the implant's integrity, which could negatively affect the subsequent drug release behavior and performance of the implants. These results provided insights to formulators on rational PLGA implant design and polymer selection.

The impact of lutein-loaded poly(lactic-co-glycolic acid) nanoparticles following topical application: An in vitro and in vivo study.

Antioxidant therapies are of interest in the prevention and management of ocular disorders such as cataracts. Although an active area of interest, topical therapy with antioxidants for the treatment of cataracts is complicated by multiple ocular anatomical barriers, product stability, and solubility. Entrapment and delivery of antioxidants with poly(lactic-co-glycolic acid) nanoparticles is a possible solution to these challenges, however, little is known regarding their effects in vitro or in vivo. Our first aim was to investigate the impact of blank and lutein loaded PLGA nanoparticles on viability and development of reactive oxygen species in lens epithelial cells in vitro. Photo-oxidative stress was induced by ultraviolet light exposure with cell viability and reactive oxygen species monitored. Next, an in vivo, selenite model was utilized to induce cataract formation in rodents. Eyes were treated topically with both free lutein and lutein loaded nanoparticles (LNP) at varying concentrations. Eyes were monitored for the development of anterior segment changes and cataract formation. The ability of nanodelivered lutein to reach the anterior segment of the eye was evaluated by liquid chromatography coupled to mass spectrometry of aqueous humor samples and liquid chromatography coupled to tandem mass spectrometry (targeted LC-MS/MS) of lenses. LNP had a minimal impact on the viability of lens epithelial cells during the short exposure timeframe (24 h) and at concentrations < 0.2 µg LNP/µl. A significant reduction in the development of reactive oxygen species was also noted. Animals treated with LNPs at an equivalent lutein concentration of 1,278 µg /mL showed the greatest reduction in cataract scores. Lutein delivery to the anterior segment was confirmed through evaluation of aqueous humor and lens sample evaluation. Topical treatment was not associated with the development of secondary keratitis or anterior uveitis when applied once daily for one week. LNPs may be an effective in the treatment of cataracts.

Carrier cascade target delivery of 5-aminolevulinic acid nanoplatform to enhance antitumor efficiency of photodynamic therapy against lung cancer.

5-Aminolevulinic acid (5-ALA) is a prodrug of porphyrin IX (PpIX). Disadvantages of 5-ALA include poor stability, rapid elimination, poor bioavailability, and weak cell penetration, which greatly reduce the clinical effect of 5-ALA based photodynamic therapy (PDT). Presently, a novel targeting nanosystem was constructed using gold nanoparticles (AuNPs) as carriers loaded with a CSNIDARAC (CC9)-targeting peptide and 5-ALA via Au-sulphur and ionic bonds, respectively, and then wrapped in polylactic glycolic acid (PLGA) NPs via self-assembly to improve the antitumor effects and reduce the side effect. The successful preparation of ALA/CC9@ AuNPs-PLGA NPs was verified using ultraviolet-visible, Fourier transform infrared spectroscopy, and X-ray photoelectron spectroscopy. The analyses revealed good sphericity with a particle size of approximately140 nm, Zeta potential of 10.11 mV, and slow-controlled release characteristic in a weak acid environment. Confocal microscopy revealed targeting of NCL-H460 cells by NPs by actively internalising CC9 and avoiding the phagocytic action of RAW264.7 cells, and live fluorescence imaging revealed targeting of tumours in tumour-bearing mice. Compared to free 5-ALA, the nanosystem displayed amplified anticancer activity by increasing production of PpIX and reactive oxygen species to induce mitochondrial pathway apoptosis. Antitumor efficacy was consistently observed in three-dimensionally cultured cells as the loss of integrity of tumour balls. More potent anti-tumour efficacy was demonstrated in xenograft tumour models by decreased growth rate and increased tumour apoptosis. Histological analysis showed that this system was not toxic, with lowered liver toxicity of 5-ALA. Thus, ALA/CC9@AuNPs-PLGA NPs deliver 5-ALA via a carrier cascade, with excellent effects on tumour accumulation and PDT through passive enhanced permeability and retention action and active targeting. This innovative strategy for cancer therapy requires more clinical trials before being implemented.

PLGA Nanoparticles Formulations Loaded With Antibiotics Induce Sustained and Controlled Antibiotics Release for Prolonged Antibacterial Action Against MRSA, and Pseudomonas aeruginosa FRD1.

The purpose of the present study was to create resorbable nanoparticles (NPs) using poly(lactic-co-glycolic acid) (PLGA) to develop novel antibacterial therapeutics for the treatment of chronic wound infections that are susceptible to recurrent infections. By first performing a release study, it was possible to predict the behavior of the different PLGA NP formulations and assess the efficacy of the nanocomposite drug delivery system. These PLGA NP formulations consisted of varying ratios of PLGA without polyvinyl alcohol (PVA) and PLGA with PVA (PLGA-PVA) (i.e., 25:75[PLGA25], 50:50[PLGA50], and 75:25[PLGA75]). Then, different antibiotics (i.e., ciprofloxacin and gentamicin) were incorporated into the PLGA NP formulations to test the antibacterial efficacy of these antimicrobial NPs against different pathogens (i.e., methicillin-resistant Staphylococcus aureus USA300 [MRSA], Pseudomonas aeruginosa FRD1, and Acinetobacter baumannii BAA1605). Of particular interest was testing against the MRSA strain USA300 and the P. aeruginosa strain FRD1. This was possible by measuring the zone of inhibition. A 3-day period was used to monitor the antibacterial efficacy of the different PLGA NP formulations (i.e., PLGA25, PLGA50, and a 1:1 combination of PLGA25:PLGA50) against A. baumannii BAA1605, MRSA, and P aeruginosa FRD1. Throughout the study, A. baumannii was a negative control and was resistant to all the PLGA NP formulations loaded with ciprofloxacin and gentamicin. At the end of the 3-day period, the PLGA and PLGA50 ciprofloxacin-loaded formulations produced zones of inhibition of 27 mm and 23 mm, respectively, against P. aeruginosa FRD1. This indicated that P. aeruginosa FRD1 was susceptible to both formulations. The mixed formulations with equal parts PLGA25:PLGA50 loaded with ciprofloxacin produced a zone of inhibition (i.e., 25 mm). This again indicated that P. aeruginosa FRD1 was susceptible to ciprofloxacin. The formulations tested against MRSA showed that only gentamicin-loaded formulations produced intermediate results, and that ciprofloxacin-loaded formulations were ineffective. The PLGA25 and the PLGA50 NP formulations loaded with gentamicin both produced zones of inhibition of 13 mm. This indicated that MRSA was intermediate to both the formulations. The PLGA25:PLGA50 loaded with gentamicin produced a zone of inhibition of 14 mm, which again showed that MRSA was intermediate to this formulation. Overall, these PLGA NP formulations showed the sustained antibacterial potential of a burst release, followed by a sustained release of antibiotics from antibiotics loaded PLGA NPs in a controlled manner. In the future, this can help prevent the emergence of recurrent infections in the treatment of chronic wounds and reduce the number of medical dressing changes.

Socket Preservation Following Tooth Extraction Using Polylactide-Polyglycolide Acid Scaffold: Radiologic and Histologic Evaluation.

PURPOSE: To assess the healing process of the extraction socket and the dimensional changes that occur after alveolar ridge preservation utilizing a polylactide-co-glycolide scaffold (PLGA). MATERIALS AND METHODS: The present study involved the extraction of 28 teeth from 14 patients. The total number of sockets was 28, which were divided into two groups consisting of 14 test sockets and 14 control sockets. The study group (SG) was subjected to socket preservation with a PLGA scaffold while the control group (CG) was left for spontaneous healing. The dimensions were measured before and after operation at 1, 3, and 5 mm below the alveolar crest horizontally and the height of buccolingual bone vertically. RESULTS: According to the histologic analyses, the PLGA scaffold was resorbed within 4 months. CBCT imaging revealed a decrease in the horizontal crest dimension at three distinct coronoapical levels in SG, measuring 2.05 ± 1.05 mm at -1 mm, 1.51 ± 0.89 mm at -3mm, and 0.92 ± 0.7 mm at-5mm.CG showed readings of 1.22 ± 1 at-1mm, 0.92 ± 0.67at-3mm, and 0.73 ± 0.69 at -5 mm. In comparison to CG, SG showed a significant reduction in horizontal losses at -1 mm. Vertical crest dimensions decreased by 1.64 ± 1.11 mm for the buccal bone height and by 1.56 ± 1.08 mm for lingual bone height in SG; in CG, the buccal and lingual bone height had mean values of 2.08 ± 1.44 mm and 1.73 ± 1.27 mm, respectively. There was no statistically significant difference observed in the vertical losses between the groups. CONCLUSIONS: Following a period of 4 months, the PLGA scaffold was completely resorbed. Based on CBCT measurements, horizontal resorption was lower than CG at -1 mm coronally.

Functionality-type and chemical-composition separation of poly(lactide-co-glycolide) using gradient elution normal-phase liquid chromatography with basic and acidic additives.

End groups of poly(Lactide-co-glycolide) (PLGA) play an important role in determining the properties of polymers for use in drug delivery systems. For instance, it has been reported that the encapsulation efficiency in PLGA microspheres varies significantly between ester-terminated and acid-terminated PLGA. More importantly, the in-vivo degradation time of such polymer excipients is influenced by the functional end-group of the copolymer used. The end group distribution in PLGA polymers has been studied using electrospray and matrix-assisted laser-desorption/ionization - high-resolution mass spectrometry. In both cases, the application of these methods is typically limited to PLGA having a molecular weight of up to 4 kDa. 13Carbon-nuclear-magnetic-resonance has also been reported as a method to differentiate and quantify PLGA end groups with a molecular weight up to 136 kDa. However, reported NMR methods take over 12 h per sample, limiting throughput.Cryoprobe NMR can reduce the time required for the process, however such NMR equipment is costly, which makes it unsuitable for the quality control of PLGA. Here, we present a normal-phase liquid chromatography method capable of resolving functionality type distribution (FTD) and, partially, chemical composition distribution (CCD) in commercial PLGA polymers obtained from ring opening polymerization. This method can separate PLGA polymers with a molecular weight of up to 183.0 kDa while also enabling the simultaneous separation of the difference of Lactic acid (LA)/Glycolic acid (GA) ratios. To achieve this, a cross-linked diol column was used with a ternary gradient from HEX to 0.1 % v/v TEA in EA to 0.1 % v/v FA in THF to allow first for the elution of mono-ester terminated PLGA, followed by the di-acid terminated. In addition, a separation of ester-terminated PLGA in the difference of the LA/GA ratio was achieved. This method is expected to aid in understanding the correlation between PLGA's FTD, CCD, and physical properties, facilitating product development and quality control.

Optimizing lornoxicam-loaded poly(lactic-co-glycolic acid) and (polyethylene glycol) nanoparticles for transdermal delivery: ex vivo/in vivo inflammation evaluation.

Aim: This study focused on developing a topical gel incorporating lornoxicam-loaded poly(lactic-co-glycolic acid) and polyethylene glycol (PLGA-PEG) blend nanoparticles to mitigate gastrointestinal (GIT) side effects and enhance therapeutic efficacy. Materials & methods: Synthesized nanoparticles were subjected to in vitro characterization, ex vivo permeation studies, and acute oral toxicity analysis post-incorporation into the gel using a S/O/W double emulsion solvent. Results & conclusion: The nanoparticles displayed a smooth, spherical morphology (170-321 nm) with increased entrapment efficiency (96.2%). LOX exhibited a permeation rate of 70-94% from the nanoparticle-infused gel, demonstrating favorable biocompatibility at the cellular level. The formulated gel, enriched with nanoparticles, holds promising prospects for drug-delivery systems and promising improved therapeutic outcomes for LOX.

[Box: see text].

Production of 5-fluorouracil-loaded PLGA nanoparticles with toroidal microfluidic system and optimization of process variables by design of experiments.

In recent decades, microfluidics has presented new opportunities for the production of nanoparticles (NPs). However, to achieve rapid clinical translation, the production of PLGA NPs in a single microfluidic channel for both the pharmaceutical research and industry without the need for scaling is still limited. The aim of this study was to accomplish the production of reproducible and stable 5-FU loaded Poly(lactic-co-glycolic acid) (PLGA) NPs, using an innovative toroidal microfluidic system, for cancer therapy. The toroidal microfluidic system enabled the production of spherical NPs ranging from 100 to 150 nm by adjusting both the TFR within the range of 5-15 mL/min and FRR between 1:3 and 1:7. A systematic assessment of critical process variables (total flow rate; TFR, flow rate ratio; FRR) for the production of PLGA NPs was conducted using Design of Experiment (DoE). The NPs, which exhibit a uniform size distribution, remained stable even after centrifugation and storage for 3 months at 4 °C. The encapsulation efficiency of drug and the concentration of NPs were not affected by changing process parameters. The effective 5-FU encapsulation into NPs resulted in a controlled in vitro drug release. Due to the controlled release profile of the 5-FU loaded PLGA NPs, the formulation was a promising candidate for mitigating the toxic side effects of free 5-FU and improving cancer treatment. In conclusion, toroidal microfluidic system enables high-volume production of stable PLGA NPs, both with and without 5-FU.

Polymeric nanoparticles produced by electrohydrodynamic atomisation for the passive delivery of imatinib.

Imatinib is a chemotherapeutic agent known to cause severe side effects when administrated systemically. Encapsulating imatinib in co-polymer poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) offers a targeted drug delivery. In this work, PLGA 50:50 and PLGA 75:25 NPs encapsulated imatinib using the electrohydrodynamic atomisation technique. All particles generated were spherical with a smooth surface with a size distribution of 455±115 nm (PLGA 50:50) and 363±147 nm (PLGA 75:25). Encapsulation of imatinib was shown to be higher than 75 % and was shown to increase the zeta potential of the loaded NPs. The release of imatinib showed an initial burst in the first 12 h, followed by different sustained releases with up to 70 %. Both types of imatinib-loaded NPs' effect on cell viability and their cellular uptake were also studied on A549 cells, and the antiproliferative effect was comparable to that of cells treated with free drugs. Finally, Rhodamine-B-loaded NP-treated cells demonstrated the cellular uptake of NPs.

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.

Evaluation of Interaction With Bio-absorbable Polyglycolic Acid Spacer and Anti-adhesive Agents Using a Rat Experimental Model.

BACKGROUND/AIM: Neskeep®, an absorbable polyglycolic acid spacer, has been developed as the optimal material for spacer placement surgery. However, preventing its severe adhesion is a crucial concern. Therefore, we aimed to identify an effective anti-adhesion agent for Neskeep® using rat models. MATERIALS AND METHODS: Animal experiments were performed using 60 rats, which underwent Neskeep® placement on the abdominal wall. Three types of anti-adhesion agents were employed, establishing four subgroups: Seprafilm®, INTERCEED®, AdSpray®, and only Neskeep® (control) groups. Rats were sacrificed on postoperative days 7, 14, and 28 to assess adhesion levels around the Neskeep® Macroscopic visual assessment with the Lauder score and histopathological evaluation were performed to assess the degree of adhesion. RESULTS: There were no significant differences in the proportion of Lauder scores on days 7 and 14 between the four groups. Histological evaluation revealed no significant differences between groups at any observation time. However, the mean Lauder scores at day 28 were 5.0, 1.6, 4.0, and 4.8 in the Neskeep®, Seprafilm®, INTERCEED®, and AdSpray® groups, respectively. The proportion of milder Lauder score was significantly higher in the Seprafilm® group on day 28. CONCLUSION: Seprafilm® may exhibit an anti-adhesive effect when used with Neskeep®.