Carbol fuchsin stain enhances detection of poly-(d, l-lactide-co-glycolide) microspheres in exenatide extended-release cutaneous injection-site foreign body reaction.

Injection of high-viscosity fluids into subcutaneous tissues may lead to a granulomatous reaction called sclerosing lipogranuloma (SL). Poly-(d,l-lactide-co-glycolide) (PLG or PLGA) microspheres are used as vehicles for extended-release drugs. Here we describe the histopathologic features of a case of SL induced by exenatide extended-release injections, and the staining pattern of PLG microspheres and microsphere remnants with carbol fuchsin.

Enhanced Anti-Tumor Activity in Mice with Temozolomide-Resistant Human Glioblastoma Cell Line-Derived Xenograft Using SN-38-Incorporated Polymeric Microparticle.

Glioblastoma multiforme (GBM) has remained one of the most lethal and challenging cancers to treat. Previous studies have shown encouraging results when irinotecan was used in combination with temozolomide (TMZ) for treating GBM. However, irinotecan has a narrow therapeutic index: a slight dose increase in irinotecan can induce toxicities that outweigh its therapeutic benefits. SN-38 is the active metabolite of irinotecan that accounts for both its anti-tumor efficacy and toxicity. In our previous paper, we showed that SN-38 embedded into 50:50 biodegradable poly[(d,l)-lactide-co-glycolide] (PLGA) microparticles (SMPs) provides an efficient delivery and sustained release of SN-38 from SMPs in the brain tissues of rats. These properties of SMPs give them potential for therapeutic application due to their high efficacy and low toxicity. In this study, we tested the anti-tumor activity of SMP-based interstitial chemotherapy combined with TMZ using TMZ-resistant human glioblastoma cell line-derived xenograft models. Our data suggest that treatment in which SMPs are combined with TMZ reduces tumor growth and extends survival in mice bearing xenograft tumors derived from both TMZ-resistant and TMZ-sensitive human glioblastoma cell lines. Our findings demonstrate that combining SMPs with TMZ may have potential as a promising strategy for the treatment of GBM.

A nanovaccine formulation of Chlamydia recombinant MOMP encapsulated in PLGA 85:15 nanoparticles augments CD4+ effector (CD44high CD62Llow) and memory (CD44high CD62Lhigh) T-cells in immunized mice.

Vaccine developmental strategies are utilizing antigens encapsulated in biodegradable polymeric nanoparticles. Here, we developed a Chlamydia nanovaccine (PLGA-rMOMP) by encapsulating its recombinant major outer membrane protein (rMOMP) in the extended-releasing and self-adjuvanting PLGA [poly (D, L-lactide-co-glycolide) (85:15)] nanoparticles. PLGA-rMOMP was small (nanometer size), round and smooth, thermally stable, and exhibited a sustained release of rMOMP. Stimulation of mouse primary dendritic cells (DCs) with PLGA-rMOMP augmented endosome processing, induced Th1 cytokines (IL-6 and IL-12p40), and expression of MHC-II and co-stimulatory (CD40, CD80, and CD86) molecules. BALB/c mice immunized with PLGA-rMOMP produced enhanced CD4+ T-cells-derived memory (CD44high CD62Lhigh), and effector (CD44high CD62Llow) phenotypes and functional antigen-specific serum IgG antibodies. In vivo biodistribution of PLGA-rMOMP revealed its localization within lymph nodes, suggesting migration from the injection site via DCs. Our data provide evidence that the PLGA (85:15) nanovaccine activates DCs and augments Chlamydia-specific rMOMP adaptive immune responses that are worthy of efficacy testing.

Electrospinning of linezolid loaded PLGA nanofibers: effect of solvents on its spinnability, drug delivery, mechanical properties, and antibacterial activities.

Objective: The choice of a desirable solvent/solvent system is fundamental for optimization of electrospinning by altering the rheological and electrostatic properties of the polymer solutions.Methods: The effects of the solvents and their properties on the viscosity and spinnability of the polymer solutions and the diameter, morphology, in vitro drug release, drug release mechanisms, antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) and mechanical properties of electrospun poly-(d,l-lactide-co-glycolide) (PLGA) nanofibers were investigated. Dichloromethane (DCM), dimethylformamide (DMF), various ratios of DCM:DMF, and 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) were used as solvents.Results: Although solutions containing DCM/DMF alone were not spinnable, different ratios of DCM:DMF and HFIP were determined as suitable solvents to produce nanofibers because of high enough conductivity, viscosity, and low enough surface tension of the solutions. The DCM:DMF ratio was highly effective on viscosity, nanofiber diameter, morphology, and linezolid release rate. The viscosity of HFIP containing solution was higher and the obtained nanofibers were thicker and smoother with better mechanical properties. The release of nanofibers containing HFIP at a concentration of 10% w/v PLGA was more prolonged than nanofibers containing DCM:DMF mixture. The effect of linezolid content on nanofibers was also investigated. As the amount of linezolid increased, nanofiber diameter and drug release increased and bead formation was observed. While antibacterial activity with nanofibers for which DCM:DMF was used, lasted for 13 days, it was extended to 16 days in nanofibers for which HFIP was used.Conclusions: Type and ratio of the solvent system affected viscosity and spinnability of the solutions, the average nanofiber diameter, morphology, in vitro activity and mechanical properties of the obtained electrospun nanofibers.

Sustained Release of Levobupivacaine, Lidocaine, and Acemetacin from Electrosprayed Microparticles: In Vitro and In Vivo Studies.

In this study, we explored the release characteristics of analgesics, namely levobupivacaine, lidocaine, and acemetacin, from electrosprayed poly(D,L-lactide-co-glycolide) (PLGA) microparticles. The drug-loaded particles were prepared using electrospraying techniques and evaluated for their morphology, drug release kinetics, and pain relief activity. The morphology of the produced microparticles elucidated by scanning electron microscopy revealed that the optimal parameters for electrospraying were 9 kV, 1 mL/h, and 10 cm for voltage, flow rate, and travel distance, respectively. Fourier-transform infrared spectrometry indicated that the analgesics had been successfully incorporated into the PLGA microparticles. The analgesic-loaded microparticles possessed low toxicity against human fibroblasts and were able to sustainably elute levobupivacaine, lidocaine, and acemetacin in vitro. Furthermore, electrosprayed microparticles were found to release high levels of lidocaine and acemetacin (well over the minimum therapeutic concentrations) and levobupivacaine at the fracture site of rats for more than 28 days and 12 days, respectively. Analgesic-loaded microparticles demonstrated their effectiveness and sustained performance for pain relief in fracture injuries.

Synthesis and Characterization of PLGA Shell Microcapsules Containing Aqueous Cores Prepared by Internal Phase Separation.

The preparation of microcapsules consisting of poly(D,L-lactide-co-glycolide) (PLGA) polymer shell and aqueous core is a clear challenge and hence has been rarely addressed in literature. Herein, aqueous core-PLGA shell microcapsules have been prepared by internal phase separation from acetone-water in oil emulsion. The resulting microcapsules exhibited mean particle size of 1.1 ± 0.39 µm (PDI = 0.35) with spherical surface morphology and internal poly-nuclear core morphology as indicated by scanning electron microscopy (SEM). The incorporation of water molecules into PLGA microcapsules was confirmed by differential scanning calorimetry (DSC). Aqueous core-PLGA shell microcapsules and the corresponding conventional PLGA microspheres were prepared and loaded with risedronate sodium as a model drug. Interestingly, aqueous core-PLGA shell microcapsules illustrated 2.5-fold increase in drug encapsulation in comparison to the classical PLGA microspheres (i.e., 31.6 vs. 12.7%), while exhibiting sustained release behavior following diffusion-controlled Higuchi model. The reported method could be extrapolated to encapsulate other water soluble drugs and hydrophilic macromolecules into PLGA microcapsules, which should overcome various drawbacks correlated with conventional PLGA microspheres in terms of drug loading and release.

Impact of surfactant selection on the formulation and characterization of microparticles for pulmonary drug delivery.

The effect of suspension stabilizers, internal aqueous phase volume and polymer amount were investigated for the production of protein loaded poly(d,l lactide-co-glycolide) (PLGA) microparticles suitable for pulmonary drug delivery. PLGA microparticles were produced adopting water-in-oil-in-water (W/O/W) solvent evaporation technique and were investigated for surface morphology, particle size, encapsulation efficiency (EE%) and in-vitro release profile. Porous surface morphologies with a narrow size distribution were observed when employing 0.5 ml internal aqueous phase; 23.04 µm (± 0.98), 15.05 µm (± 0.27) and 22.89 µm (±0.41) for PVA, Tween 80 and oleic acid. Porous microparticles exhibited increased size and reduction in EE% with increasing internal aqueous phase, with non-porous microparticles produced when adopting 2.0 ml internal aqueous phase. The selection of stabilizer influences the size of the pores formed thus offers potential for the aerodynamic properties of the microparticles to be manipulated to achieve suitable aerosolization characteristics for pulmonary delivery of proteins.

In vitro evaluation of suspoemulsions for in situ-forming polymeric microspheres and controlled release of progesterone.

One possibility to obtain a higher dose of drug in a lower formulation volume can be by using of saturated quantity of drug in one of the phases of an emulsion. These formulations are called suspoemulsions (S/O/W). When a hydrophobic polymer is added to the organic phase of suspoemulsions, these formulations can be used to entrap the drug inside microspheres after in situ precipitation of the polymer-drug-excipients mix. In this work, performance and stability of progesterone suspensions in triacetin as organic phase of suspoemulsions were evaluated. These formulations were compared with O/W emulsions. Mathematical models were used to study in vitro release profiles. The results confirmed that S/O/W systems could be an attractive alternative to O/W formulations for the entrapment of progesterone inside poly(d,l-lactide-co-glycolide) microspheres. Diffusive-based models fit the in vitro release of progesterone from in situ-formed microspheres. For longer release periods, a time-dependent diffusion coefficient was successfully estimated.

Synthesis of uniform poly(d,l-lactide) and poly(d,l-lactide-co-glycolide) microspheres using a microfluidic chip for comparison.

Applications of poly(l-lactide) (PLA) and poly(d,l-lactide-co-glycolide) (PLGA) microspheres are widely used in the biomedical and pharmaceutical fields. The effects of PLA/PLGA on microsphere properties when using conventional particulate preparation methods are not easily defined due to the uncontrollable particle size and size distribution. This study was aimed to synthesize uniform PLA and PLGA microspheres using a phenol formaldehyde resin-based microfluidic chip, which has the advantage of being solvent-resistant, flexible, and is readily disassembled for cleaning. The proposed chip can rapidly fabricate reproducible PLA and PLGA microspheres. Uniform emulsion droplets can be achieved by hydrodynamic flow focusing. After solvent evaporation, the free-flowing PLA and PLGA microspheres have a high level of morphological uniformity and size, allowing for a clear comparison of material effects. The results indicate that the sizes of the PLA and PLGA microspheres for the various flow rates of dispersed/continuous phases are very similar. The PLA/PLGA materials do not have a significant effect on particle size, but the particle surface indicates a different morphology. The result of the cytotoxicity evaluation shows no difference between PLA and PLGA and ensures the biocompatibility of both prepared PLA and PLGA microspheres for biomedical and pharmaceutical applications in the future.

Translocator protein ligand-PLGA conjugated nanoparticles for 5-fluorouracil delivery to glioma cancer cells.

Translocator protein 18 kDa (TSPO) is a promising target for molecular imaging and for targeted drug delivery to tumors overexpressing TSPO. In our previous work, new macromolecular conjugates with a high affinity and selectivity for TSPO were prepared by conjugating the biodegradable poly(d,l-lactic-co-glycolic acid) (PLGA) polymer with two potent and selective TSPO ligands, namely, compounds 1 and 2. Based on this, nanoparticle delivery systems (NPs), employing TSPO ligand-PLGA conjugated (PLGA-TSPO) polymers, were prepared. Furthermore, to evaluate the ability of the new NPs to be used as a drug delivery systems for anticancer therapy, PLGA-TSPO NPs were loaded with 5-fluorouracil (5-FU), chosen as a model hydrophilic anticancer drug. The main goal of this work was to investigate the synergistic potential of using NP conjugates PLGA-TSPO, TSPO ligands being pro-apoptotic agents, to simultaneously deliver a cytotoxic anticancer drug. To better highlight the occurrence of synergistic effects, dual drug loaded PLGA NPs (PLGA NPs/5-FU/1) and dual drug loaded PLGA-TSPO NPs (PLGA-TSPO NPs/5-FU/1), with 5-FU and TSPO ligand 1 physically incorporated together, were also prepared and characterized. The particle size and size distribution, surface morphology, and drug encapsulation efficiency, as well as the drug release kinetics, were investigated. In vitro cytotoxicity studies were carried out on C6 glioma cells overexpressing TSPO, and to evaluate the potential uptake of these nanoparticulate systems, the internalization of fluorescent labeled PLGA-TSPO NPs (FITC-PLGA-TSPO NPs) was also investigated by fluorescence microscopy. Results demonstrated that PLGA-TSPO NPs/5-FU and dual drug loaded PLGA NPs/5-FU/1 and PLGA-TSPO NPs/5-FU/1 could significantly enhance toxicity against human cancer cells due to the synergistic effect of the TSPO ligand 1 with the anticancer drug 5-FU.

Ketoprofen enantioseparation with a Cinchona alkaloid based stationary phase: enantiorecognition mechanism and release studies.

With the present contribution, we demonstrate that the baseline separation of ketoprofen enantiomers can be successfully achieved (α = 1.09; R(S) = 1.60) in the reversed-phase mode of elution with a commercially available anion-exchange-based chiral stationary phase, incorporating the quinine 2,6-diisopropylphenyl carbamate derivative as the enantioresolving unit. Focused modification of the eluent composition indicated a stereoselective role of hydrophobic and π-π interactions between the selector and selectand units, besides the prime ionic intermolecular interaction. The mechanistic hypotheses based on the chromatographic data were confirmed by in silico molecular dynamic simulations, which allowed us to establish the network of selector-selectand interactions underlying the stereorecognition process at a molecular level. The validated method was successfully used to evaluate the drug content and release profile of ketoprofen-loaded polymeric film, showing drug homogeneous distribution into the film and no preferential interactions between the polymer and one of the enantiomers, with the racemate released at each time point.

Crucial CD8(+) T-lymphocyte cytotoxic role in amphotericin B nanospheres efficacy against experimental visceral leishmaniasis.

This work aims to develop poly(d,l-lactide-co-glycolide) (PLGA)-nanospheres containing amphotericin B (AmB) with suitable physicochemical properties and anti-parasitic activity for visceral leishmaniasis (VL) therapy. When compared with unloaded-PLGA-nanospheres, the AmB-loaded PLGA-nanospheres displayed an increased particle size without affecting the polydispersity and its negative surface charge. AmB stability in the PLGA-nanospheres was >90% over 60-days at 30°C. The AmB-PLGA-nanospheres demonstrated significant in vitro and in vivo efficacy and preferential accumulation in the visceral organs. In addition, an immune-modulatory effect was observed in mice treated with AmB-PLGA-nanospheres, correlating with improved treatment efficacy. The in vitro cytotoxic response of the T-lymphocytes revealed that AmB-PLGA-nanospheres efficacy against VL infection was strictly due to the action of CD8(+)- but not CD4(+)-T lymphocytes. Overall, we demonstrate a crucial role for CD8(+) cytotoxic T lymphocytes in the efficacy of AmB-PLGA nanospheres, which could represent a potent and affordable alternative for VL therapy. FROM THE CLINICAL EDITOR: This study demonstrates a crucial role for CD8+ T lymphocytes in eliminating visceral leishmaniasis in a murine model by enhancing the cytotoxic efficacy of CD8+ T-cells via amphotericin-B-PLGA nanospheres, paving a way to a unique, potentially more potent and cost-effective therapeutic strategy.

Applicability of non-halogenated methyl propionate to microencapsulation.

Applicability of methyl propionate to microencapsulation was evaluated with regard to volatility, capability of forming emulsions, and their quality. An emulsion-based technique was then developed to encapsulate progesterone into poly-d,l-lactide-co-glycolide microspheres. Their characteristics were compared with those prepared using ethyl acetate. Our results demonstrated that methyl propionate had greater evaporative tendency and less water miscibility than ethyl acetate did. The former allowed us to prepare good microspheres. Their average volume mean diameter was 68.3 ± 1.7 µm with a span index of 0.91 ± 0.13. Progesterone did not undergo polymorphic transition during microencapsulation, and its encapsulation efficiency ranged from 41.80 ± 1.83 to 85.64 ± 1.95%. Residual methyl propionate in various microspheres was found to be 0.97 ± 0.03 to 1.54 ± 0.07%. Such microsphere characteristics were quite similar to those prepared by the ethyl acetate-based microencapsulation process. Overall, our findings reflect that methyl propionate has a potential to become an invaluable solvent for microencapsulation.

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].

In vivo research on 3D-printed composite PLGA and PDLLA-HA absorbable scaffolds for repairing radius defects in rabbits.

OBJECTIVES: Despite being an important research topic in oral biomaterials, few studies have demonstrated the differences between poly(d,l-lactide-co-glycolide)/hydroxyapatite (PLGA/HA) and poly(d,l-lactic acid)/hydroxyapatite (PDLLA/HA). In this study, PLGA/HA and PDLLA/HA scaffolds were prepared using three-dimensional (3D) printing technology and implanted into radius defects in rabbits to assess their effects on bone regeneration. METHODS: In this study, 6 mm × 4 mm bone defects were generated in the bilateral radii of rabbits. 3D-printed PLGA/HA and PDLLA/HA scaffolds were implanted into the defects. X-ray imaging, micro-computed tomography, and hematoxylin-eosin staining were performed to observe the degradation of the materials, the presence of new bone, and bone remodeling in the bone defect area. RESULTS: The PLGA/HA scaffolds displayed complete degradation at 20 weeks, whereas PDLLA/HA scaffolds exhibited incomplete degradation. Active osteoblasts were detected in both groups. The formation of new bone, bone marrow cavity reconstruction, and cortical bone remodeling were better in the PLGA/HA group than in the PDLLA/HA group. CONCLUSIONS: PLGA/HA scaffolds performed better than PDLLA/HA scaffolds in repairing bone defects, making the former scaffolds more suitable as bone substitutes at the same high molecular weight.

The role of artificial intelligence in generating original scientific research.

Artificial intelligence (AI) is a revolutionary technology that is finding wide application across numerous sectors. Large language models (LLMs) are an emerging subset technology of AI and have been developed to communicate using human languages. At their core, LLMs are trained with vast amounts of information extracted from the internet, including text and images. Their ability to create human-like, expert text in almost any subject means they are increasingly being used as an aid to presentation, particularly in scientific writing. However, we wondered whether LLMs could go further, generating original scientific research and preparing the results for publication. We taskedGPT-4, an LLM, to write an original pharmaceutics manuscript, on a topic that is itself novel. It was able to conceive a research hypothesis, define an experimental protocol, produce photo-realistic images of 3D printed tablets, generate believable analytical data from a range of instruments and write a convincing publication-ready manuscript with evidence of critical interpretation. The model achieved all this is less than 1 h. Moreover, the generated data were multi-modal in nature, including thermal analyses, vibrational spectroscopy and dissolution testing, demonstrating multi-disciplinary expertise in the LLM. One area in which the model failed, however, was in referencing to the literature. Since the generated experimental results appeared believable though, we suggest that LLMs could certainly play a role in scientific research but with human input, interpretation and data validation. We discuss the potential benefits and current bottlenecks for realising this ambition here.

A Dexamethasone-Loaded Polymeric Electrospun Construct as a Tubular Cardiovascular Implant.

Cardiovascular tissue engineering is providing many solutions to cardiovascular diseases. The complex disease demands necessitating tissue-engineered constructs with enhanced functionality. In this study, we are presenting the production of a dexamethasone (DEX)-loaded electrospun tubular polymeric poly(l-lactide) (PLA) or poly(d,l-lactide-co-glycolide) (PLGA) construct which contains iPSC-CMs (induced pluripotent stem cell cardiomyocytes), HUVSMCs (human umbilical vein smooth muscle cells), and HUVECs (human umbilical vein endothelial cells) embedded in fibrin gel. The electrospun tube diameter was calculated, as well as the DEX release for 50 days for 2 different DEX concentrations. Furthermore, we investigated the influence of the polymer composition and concentration on the function of the fibrin gels by imaging and quantification of CD31, alpha-smooth muscle actin (αSMA), collagen I (col I), sarcomeric alpha actinin (SAA), and Connexin 43 (Cx43). We evaluated the cytotoxicity and cell proliferation of HUVECs and HUVSMCs cultivated in PLA and PLGA polymeric sheets. The immunohistochemistry results showed efficient iPSC-CM marker expression, while the HUVEC toxicity was higher than the respective HUVSMC value. In total, our study emphasizes the combination of fibrin gel and electrospinning in a functionalized construct, which includes three cell types and provides useful insights of the DEX release and cytotoxicity in a tissue engineering perspective.

Use of low-field NMR and rheology to evaluate the microstructure and stability of a poly(d,l-lactide-co-glycolide)-based W/O emulsion to be processed by spray drying.

Drug-loaded emulsions for spray drying should be optimised for their rheological behaviour and stability under operating conditions, as this is essential for achieving the desired physicochemical properties of the final dry product. Our aim was therefore to investigate the structure and stability of a water-in-oil (W/O) emulsion containing vancomycin hydrochloride as the active ingredient in the aqueous phase, poly(d,l-lactide-co-glycolide) as the structural polymer in the dichloromethane-based organic phase, and various stabilisers using low-field nuclear magnetic resonance (LF NMR) and rheological characterisation. Four emulsions were tested, namely-one without stabiliser, one with Poloxamer® 407, one with chitosan and Span™ 80 and one with chitosan only. The theoretical interpretation of the rheological data allowed the determination of the velocity and the shear rate/stress profiles inside the feed path of the W/O emulsion, aspects that are critical for the industrial scale-up of the emulsion drying process. In addition, LF NMR demonstrated that shaking was sufficient to restore the original emulsion structure and that the droplet size of all emulsions was in the range of 1-10 µm, although the emulsion with chitosan had the narrowest droplet size distribution and the higher zero shear viscosity, which accounts for the increased long-term stability due to impeded droplets movement.

Potential of Aligned Electrospun PLGA/SIS Blended Nanofibrous Membrane for Tendon Tissue Engineering.

Tendons are responsible for transmitting mechanical forces from muscles to bones for body locomotion and joint stability. However, tendons are frequently damaged with high mechanical forces. Various methods have been utilized for repairing damaged tendons, including sutures, soft tissue anchors, and biological grafts. However, tendons experience a higher rate of retear post-surgery due to their low cellularity and vascularity. Surgically sutured tendons are vulnerable to reinjury due to their inferior functionality when compared with native tendons. Surgical treatment using biological grafts also has complications such as joint stiffness, re-rupture, and donor-site morbidity. Therefore, current research is focused on developing novel materials that can facilitate the regeneration of tendons with histological and mechanical characteristics similar to those of intact tendons. With respect to the complications in association with the surgical treatment of tendon injuries, electrospinning may be an alternative for tendon tissue engineering. Electrospinning is an effective method for fabrication of polymeric fibers with diameters ranging from nanometers to micrometers. Thus, this method produces nanofibrous membranes with an extremely high surface area-to-volume ratio, which is similar to the extracellular matrix structure, making them suitable candidates for application in tissue engineering. Moreover, it is possible to fabricate nanofibers with specific orientations that are similar to those of the native tendon tissue using an adequate collector. To increase the hydrophilicity of the electrospun nanofibers, natural polymers in addition to synthetic polymers are used concurrently. Therefore, in this study, aligned nanofibers composed of poly-d,l-lactide-co-glycolide (PLGA) and small intestine submucosa (SIS) were fabricated using electrospinning with rotating mandrel. The diameter of aligned PLGA/SIS nanofibers was 568.44 ± 135.594 nm, which closely resembles that of native collagen fibrils. Compared to the results of the control group, the mechanical strength exhibited by the aligned nanofibers was anisotropic in terms of break strain, ultimate tensile strength, and elastic modulus. Elongated cellular behavior was observed in the aligned PLGA/SIS nanofibers using confocal laser scanning microscopy, indicating that the aligned nanofibers were highly effective with regard to tendon tissue engineering. In conclusion, considering its mechanical properties and cellular behavior, aligned PLGA/SIS is a promising candidate for tendon tissue engineering.

Hyaluronate decorated polyethylene glycol linked poly(lactide-co-glycolide) nanoparticles encapsulating MUC-1 peptide augmented mucosal immune response in Balb/c mice through inhalation route.

BACKGROUND AND OBJECTIVES: NSCLC (Non-Small Cell Lung Cancer) clutches highest mortality rate in man and women globally. The present study was conducted to target MUC-1 peptide (M-1) into antigen presenting cells by cargo the peptide into hyaluronic acid decorated polyethylene glycol linked poly (D, l-lactide-co-glycolide) nanoparticles (M-1-PL-co-GA-PEG-sHA-NPs) for generating mucosal immunity through inhalation (i.h.) route. METHODOLOGY AND RESULTS: The mean particle size and surface charge of M-1-PL-co-GA-PEG-sHA-NPs was measured to be 136.2 ± 18.38-nm and - 28.34 ± 6.77-mV, respectively, prepared by non-aggregated emulsion-diffusion evaporation method. The 28.42% percentage release of M-1 peptide from M-1-PL-co-GA-PEG-NPs was observed to be at 2 h and 95.29% at 8 h while the percentage release of M-1 peptide from M-1-PL-co-GA-PEG-sHA-NPs was observed to be 26.02% at 4 h and 97.95% at 24 h that proved the prolonged release of antigen. M-1-PL-co-GA-PEG-sHA-NPs demonstrated higher (P < 0.05) cellular uptake of 86.2% in RAW 264.7 cells in comparison to 27.6% of M-1-PL-co-GA-PEG-NPs. In addition, M-1-PL-co-GA-PEG-sHA-NPs induced remarkably (P < 0.05) elevated release of 80.6-pg/ml of TNF-α in comparison to 5-pg/ml by culture medium and 57.9-pg/ml of TNF-α by M-1-PL-co-GA-PEG-NPs. Similarly, M-1-PL-co-GA-PEG-sHA-NPs persuade remarkably (P < 0.05) elevated release of 225-pg/ml of IL-1ß in comparison to 47-pg/ml by culture medium and 161.9-pg/ml of IL-1ß by M-1-PL-co-GA-PEG-NPs. M-1-PL-co-GA-PEG-sHA-NPs might have been endocytosed through receptor mediated pathway owing to presence of sHA. Mice immunized through i.h. route with M-1-PL-co-GA-PEG-sHA-NPs induced strong (P < 0.05) IgA antibody titre as compared to M-1-PL-co-GA-PEG-NPs and M-1 peptide in dose-dosage regimen. CONCLUSION: M-1-PL-co-GA-PEG-sHA-NPs nanovaccine warrants further analysis in xenograft model of NSCLC to showcase its antitumor capability.