Co-glycolic Acid Research Articles

Development of erythromycin loaded PLGA nanoparticles for improved drug efficacy and sustained release against bacterial infections and biofilm formation

Bacterial infections are a common cause of sepsis, often leading to high patient mortality. Such infections are challenging to treat due to bacterial resistance to many existing drugs. Erythromycin (Ery) is a macrolide antibiotic used against bacterial infections with reported resistance. Recently, synthetic poly-lactide co-glycolic acid (PLGA) polymer nanoparticles (NPs) have displayed improved drug delivery characteristics and biocompatibility. In this study, PLGA-Ery NPs were synthesized by the o/w emulsion diffusion method, having a particle size of 159 ± 23 nm and displayed 71.89 % of encapsulation efficiency. The PLGA-Ery NPs showed 1.5, 2.1 and 1.5-fold improved MIC and antibacterial efficacy against E. coli, S. aureus, and P. aeruginosa, respectively than the pure drug. As illustrated by scanning electron microscopy, PLGA-Ery NPs caused damage to the bacterial cell walls. Furthermore, a surface coating with PLGA-Ery NPs on a glass surface showed efficient inhibition (>90 %) of the biofilm formation by P. aeruginosa, as determined by fluorescence microscopy and MTT assay. This study demonstrates that PLGA-Ery NPs can increase the efficiency of erythromycin and can suppress the growth and biofilm formation of P. aeruginosa. Such polymeric nanoparticles drug nanoformulations have potential as an antimicrobial and as a surface coating for medical devices.

Development and Characterization of Oxiconazole Loaded Plga Nanogel.

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

An Insight into Biodegradable Polymers and their Biomedical Applications for Wound Healing.

Biodegradable polymers, encompassing both natural and synthetic polymers, have demonstrated efficacy as carriers for synthetic drugs, natural bioactive molecules, and inorganic metals. This is due to their ability to control the release of these substances. As a result, various advanced materials, such as nanoparticle- loaded hydrogels, nanofibrous scaffolds, and nanocomposites, have been developed. These materials have shown promise in enhancing processes, such as cell proliferation, vascular angiogenesis, hair growth, and wound healing management. Natural polymers, including hyaluronic acid, collagen, chitosan, gelatin, and alginate, as well as synthetic polymers like polylactic acid, polyglycolic acid, polylactic co-glycolic acid, and PCA, have significant potential for promoting wound healing. This study examines the advancements in biodegradable polymers for wound healing, specifically focusing on each polymer and its distinctive formulations. It also discusses the in vitro experiments conducted using different cell lines, as well as the in vivo studies that explore the numerous uses of these polymers in wound healing. The discussion also included the exploration of modifications or combinations of several polymers, as well as surface changes, in order to produce synergistic effects and address the limitations of individual polymers. The goal was to expedite the healing process of different chronic wounds. Due to this, there have been notable advancements in the technological use of polymeric mixes, including biodegradable polymer-based scaffolds, which have accelerated the process of wound healing.

A Comparative Study of Using Poly (D, L, Lactide-co-Glycolic Acid) and Chitosan Nanoparticle as Vaccine Delivery System for a Recombinant Fusion Protein of Newcastle Disease Virus

Introduction: The more effective method of preventing many infectious diseases is vaccination. Numerous infectious diseases that affect both humans and animals have significantly decreased as a result of routine immunization. Aim: The present study aimed to compare the efficacy of in-house built chitosan and Polylactide coglycolic acid (PLGA) nanoparticles coupled with Pichia pastoris expressed immunogenic fusion (F) protein of Newcastle disease (ND). Objectives: Synthesis of biodegradable nanoparticles such as PLGA and chitosan offers a promising opportunity as a vaccine delivery system. Methods: Chitosan nanoparticles and PLGA nanoparticles were synthesized by ionic gelation, and double emulsion solvent evaporation, respectively, and the size was 38.6± 0.84 nm and 320 ±1.5nm, respectively. They demonstrated good epitope integrity of recombinant fusion protein and in vitro release kinetics studies have proved consistent release profile of protein Results: In vivo pathogenicity assay of separately injected nanoparticles has proved no abnormal signs and mortality in chickens. Specific pathogen-free (SPF) chicks were vaccinated with chitosan and PLGA nanoparticles and a recombinant fusion protein of the ND virus. It was demonstrated that PLGA nanoparticles coupled with a fusion protein of Newcastle disease virus conferred a marginally better immune response than chitosan nanoparticles. Comparative study-based results showed that PLGA-based nanoparticles proved a better vaccine delivery vehicle and generated an effective immune response without needing further adjuvants. Conclusion: The present study is a scientific platform for developing the PLGA-based vaccine delivery vehicle to improve immune responses against many infectious diseases.

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.

Construction of Mesenchymal Stem Cell-Derived Artificial Human Urinary Bladder: A Preliminary Study

Objective: The present study aimed to obtain the required cells and select a suitable scaffold material for constructing an artificial bladder using the tissue engineering approach. 
 Materials and methods: The convenience of obtaining human adipose tissue-derived stem cells (hADMSCs) was used in this study. It was attempted to differentiate these cells into smooth muscle cells (SMC), which are present along the wall of the bladder. Urothelial cells were enzymatically isolated from tissue biopsies. Synthetic (poly-lactide co-glycolic acid, PLGA) and natural (chitosan) polymers were used in scaffold fabrication using a tissue engineering approach.
 Results: In the cellular experiments, urothelial cells couldn’t be cultured in polystyrene culture vessels in vitro and required a support material to maintain viability. Better results were obtained with the feeder layer. The hADMSCs exhibited the expected morphological changes in the serum-rich medium content in the SMC differentiation experiments. Chitosan, biocompatible and biodegradable, was mixed with PLGA as an alternative scaffold combination.
 Conclusion: This study indicated that hADMSCs-derived smooth muscle cells and biopsy-isolated urothelial cells cultured on hybrid chitosan–PLGA scaffolds with appropriate physical properties could serve as a suitable model for tissue-engineered artificial bladder construction.

Combining PLGA microspheres loaded with Liver X receptor agonist GW3965 with a chitosan nerve conduit can promote the healing and regeneration of the wounded sciatic nerve.

Globally, peripheral nerve injury (PNI) is a common clinical issue. Successfully repairing severe PNIs has posed a major challenge for clinicians. GW3965 is a highly selective LXR agonist, and previous studies have demonstrated its positive protective effects in both central and peripheral nerve diseases. In this work, we examined the potential reparative effects of GW3965-loaded polylactic acid co-glycolic acid microspheres in conjunction with a chitosan nerve conduit for peripheral nerve damage. The experiment revealed that GW3965 promoted Schwann cell proliferation and neurotrophic factor release in vitro. In vivo experiments conducted on rats showed that GW3965 facilitated the restoration of motor function, promoted axon and myelin regeneration in the sciatic nerve, and enhanced the microenvironment of nerve regeneration. These results offer a novel therapeutic approach for the healing of nerve damage. Overall, this work provides valuable insights and presents a promising therapeutic strategy for addressing PNI.

Nanoparticles and Their Antibacterial Application in Endodontics.

Root canal treatment represents a significant challenge as current cleaning and disinfection methodologies fail to remove persistent bacterial biofilms within the intricate anatomical structures. Recently, the field of nanotechnology has emerged as a promising frontier with numerous biomedical applications. Among the most notable contributions of nanotechnology are nanoparticles, which possess antimicrobial, antifungal, and antiviral properties. Nanoparticles cause the destructuring of bacterial walls, increasing the permeability of the cell membrane, stimulating the generation of reactive oxygen species, and interrupting the replication of deoxyribonucleic acid through the controlled release of ions. Thus, they could revolutionize endodontics, obtaining superior results and guaranteeing a promising short- and long-term prognosis. Therefore, chitosan, silver, graphene, poly(lactic) co-glycolic acid, bioactive glass, mesoporous calcium silicate, hydroxyapatite, zirconia, glucose oxidase magnetic, copper, and zinc oxide nanoparticles in endodontic therapy have been investigated in the present review. The diversified antimicrobial mechanisms of action, the numerous applications, and the high degree of clinical safety could encourage the scientific community to adopt nanoparticles as potential drugs for the treatment of endodontic diseases, overcoming the limitations related to antibiotic resistance and eradication of the biofilm.

Invited Session II: Retinal remodeling and regeneration: Developing autologous iPSC-RPE therapy for the treatment of AMD patients.

Age-related macular degeneration (AMD) is one the leading causes of vision loss in older people in the Western world. The disease is caused by degeneration of the retinal pigment epithelium (RPE) monolayer that supports photoreceptors. We used induced pluripotent stem cells (iPSC) to develop an autologous cell replacement therapy for treating dry AMD patients. Patients' blood cells were reprogrammed into iPSCs and differentiated iPSCs into RPE cells using a protocol developed in our lab. RPE cells were matured on a biodegradable polylactic co-glycolic acid (PLGA) scaffold for five weeks. Quality control assays confirmed the iPSC-RPE patch's purity, maturity, and functionality. Pre-clinical studies in rats and pigs demonstrated the safety and efficacy of iPSC-RPE-patch. Immune-compromised rats transplanted with a 0.5 mm iPSC-RPE patch showed no signs of tumor formation after nine months, confirming the safety profile. We laser-injured the RPE monolayer in the visual streak of pig eyes and, after 48 hours, transplanted the patch. Optical coherence tomography (OCT) confirmed the integration of the patch. A multi-focal electroretinogram (ERG) showed that the retinal layers' electric response was much higher than the lasered area without the implant. We started a phase I/IIa trial for an autologous iPSC-RPE patch to treat AMD. This ongoing trial will test the safety, feasibility, and integration of the iPSC-RPE patch in 12 AMD patients.

Folic/lactobionic acid dual-targeted polymeric nanocapsules for potential treatment of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a malignant tumor that affects many patients diagnosed with hepatic cell inflammation and liver cirrhosis. Targeted polymeric nanocapsules could facilitate the internalization and accumulation of anticancer drugs. Dual-targeted folic acid/lactobionic acid-poly lactic co-glycolic acid nanocapsules (NCs) were prepared and loaded with pterostilbene (PTN) and characterized for their physicochemical properties, as well as in vitro and in vivo anticancer activity. NCs displayed a size of 222nm, zeta potential of - 16.5mV, and sustained release for 48h. The IC50 of PTN NCs (5.87 ± 0.8µg/mL) was 20 times lower than unencapsulated PTN (121.26 ± 9.42µg/mL) on HepG2 liver cancer cells owing to the enhanced cellular uptake of the former, as delineated by flow cytometry. In vivo study on HCC-induced animals delineated the superiority of the dual-targeted NCs over the unencapsulated PTN, which significantly reduced the liver markers ALT, AST, and ALP, as well as the tumor-related markers AFP and Bcl2, and elevated the anti-apoptotic marker caspase 3. Furthermore, the NCs significantly reduced the oxidative stress and exhibited almost comparable histological features to the normal group. Therefore, it can be concluded that the dual-ligated folic acid/lactobionic acid nanocapsules can be considered a promising potential treatment option for hepatocellular carcinoma.

Combination nanochemotherapy of brain tumor using polymeric nanoparticles loaded with doxorubicin and paclitaxel: An in vitro and in vivo study

This study aims to overcome physiological barriers and increase the therapeutic index for the treatment of glioblastoma (GBM) tumors by using Paclitaxel (PTX) loaded Poly(lactic co-glycolic acid) nanoparticles (PTX-PLGA-NPs) and Doxorubicin (DOX) loaded Poly (lactic co-glycolic acid) nanoparticles (DOX-PLGA-NPs). The hydrodynamic diameter of nanoparticles (NPs) was characterized by dynamic light scattering (DLS) which was 94 ± 4 nm and 133 ± 6 nm for DOX-PLGA-NPs, and PTX-PLGA-NPs, respectively. The zeta potential for DOX-PLGA-NPs and PTX-PLGA-NPs were −15.2 ± 0.18 mV and −17.3 ± 0.34 mV, respectively. The cytotoxicity of PTX-PLGA-NPs and DOX-PLGA-NPs was augmented compared to DOX and PTX on C6 GBM cells. The Lactate dehydrogenase (LDH) tests for various formulations were carried out. The results indicated that the amount of released LDH was 262 ± 7.84 U.L-1 at the concentration of 2 mg/mL in the combination therapy, which was much higher than other groups (DOX-PLGA-NPs (210 ± 6.92 U.L-1), PTX-PLGA-NPs (201 ± 8.65 U.L-1), DOX (110 ± 9.81 U.L-1), PTX (95 ± 5.02 U.L-1) and PTX + DOX (67 ± 4.89 U.L-1)). MRI results of the combination therapy of PTX-PLGA-NPs and DOX-PLGA-NPs indicated that GBM tumor size decreased considerably compared to the other formulations. Also, combination therapy of PTX-PLGA-NPs and DOX-PLGA-NPs demonstrated a longer median survival of more than 80 days compared to PTX (38 days), DOX (37 days) and PTX + DOX (48 days), PTX-NPs (58 days) and DOX-NPs (62 days). The results of locomotion, body weight, rearing and grooming assays indicated that combination therapy of PTX-PLGA-NPs and DOX-PLGA-NPs had the most positive effect on the movements of rats compared to the other formulations.

Exploiting immunostimulatory mechanisms of immunogenic cell death to develop membrane-encapsulated nanoparticles as a potent tumor vaccine

Vaccine is one of the most promising strategies for cancer immunotherapy; however, there are no therapeutic cancer vaccine achieving significant clinical efficacy till now. The main limiting factors include the immune suppression and escape mechanisms developed by tumor and not enough capacity of vaccines to induce a vigorous anti-tumor immunity. This study aimed to develop a strategy of membrane-based biomimetic nanovaccine and investigate the immunological outcomes of utilizing the unique immunostimulatory mechanisms derived of immunogenic cell death (ICD) and of fulfilling a simultaneous nanoscale delivery of a highlighted tumor antigen and broad membrane-associated tumor antigens in the vaccine design. TC-1 tumor cells were treated in vitro with a mixture of mitoxantrone and curcumin for ICD induction, and then chitosan (CS)-coated polylactic co-glycolic acid (PLGA) nanoparticles loaded with HPV16 E744-62 peptides were decorated with the prepared ICD tumor cell membrane (IM); further, the IM-decorated nanoparticles along with adenosine triphosphate (ATP) were embedded with sodium alginate (ALG) hydrogel, And then, the immunological features and therapeutic potency were evaluated in vitro and in vivo. The nanovaccine significantly stimulated the migration, antigen uptake, and maturation of DCs in vitro, improved antigen lysosome escape, and promoted the retention at injection site and accumulation in LNs of the tumor antigen in vivo. In a subcutaneously grafted TC-1 tumor model, the therapeutic immunization of nanovaccine elicited a dramatical antitumor immunity. This study provides a strategy for the development of tumor vaccines.Graphical

A composite membrane with microtopographical morphology to regulate cellular behavior for improved tissue regeneration.

Tissue engineering scaffolds with specific surface topographical morphologies can regulate cellular behaviors and promote tissue repair. In this study, poly lactic(co-glycolic acid) (PLGA)/wool keratin composite guided tissue regeneration (GTR) membranes with three types of microtopographies (three groups each of pits, grooves and columns, thus nine groups in total) were prepared. Then, the effects of the nine groups of membranes on cell adhesion, proliferation and osteogenic differentiation were examined. The nine different membranes had clear, regular and uniform surface topographical morphologies. The 2 µm pit-structured membrane had the best effect on promoting the proliferation of bone marrow mesenchymal stem cells(BMSCs) and periodontal ligament stem cells (PDLSCs), while the 10 µm groove-structured membrane was the best for inducing osteogenic differentiation of BMSCs and PDLSCs. Then, we investigated the ectopic osteogenic, guided bone tissue regeneration and guided periodontal tissue regeneration effects of the 10 µm groove-structured membrane combined with cells or cell sheets. The 10 µm groove-structured membrane/cell complex had good compatibility and certain ectopic osteogenic effects, and the 10 µm groove-structured membrane/cell sheet complex promoted better bone repair and regeneration and periodontal tissue regeneration. Thus, the 10 µm groove-structured membrane shows potential to treat bone defects and periodontal disease. STATEMENT OF SIGNIFICANCE: PLGA/wool keratin composite GTR membranes with microcolumn, micropit and microgroove topographical morphologies were prepared by dry etching technology and the solvent casting method. The composite GTR membranes had different effects on cell behavior. The 2 µm pit-structured membrane had the best effect on promoting the proliferation of rabbit BMSCs and PDLSCs and the 10 µm groove-structured membrane was the best for inducing the osteogenic differentiation of BMSCs and PDLSCs. The combined application ofa 10 µm groove-structured membrane and PDLSC sheet can promote better bone repair and regeneration as well as periodontal tissue regeneration. Our findings may have significant potential for guiding the design of future GTR membranes with topographical morphologies and clinical applications of the groove-structured membrane/cell sheet complex.

Intramuscularly Administered PLGA Microparticles for Sustained Release of Rivastigmine: In Vitro, In Vivo and Histological Evaluation

Rivastigmine is an acetylcholinesterase (AchE) and butyrylcholinesterase (BchE) inhibitor drug approved by the US Food and Drug Administration (FDA) for the treatment of mild to moderate dementia of Alzheimer's type. However, its first-pass metabolism and gastrointestinal side effects negatively affect the tolerability and efficacy of oral therapy. These adverse effects could be avoided with the use of a sustained -release formulation as an intramuscular (IM) administration system. The objective of this work was to develop polylactic co-glycolic acid (PLGA) microparticles for the sustained release of rivastigmine and to evaluate its stability during storage, tissue tolerance, in vitro release, and in vivo pharmacokinetics after its IM administration. The microparticles were made by the solvent evaporation emulsion method. A series of formulation parameters (the type of polymer used, the amount of polymer used, the initial amount of rivastigmine, and the volume of PVA 0.1% w/v) were studied to achieve an encapsulation efficiency (EE) and a rivastigmine load of 54.8 ± 0.9% and 3.3 ± 0.1%, respectively. The microparticles, whose size was 56.1 ± 2.8 μm, had a spherical shape and a smooth surface. FT-IR analysis showed that there is no chemical interaction between rivastigmine and the polymer. PLGA microparticles maintain rivastigmine retained and stable under normal (5 ± 3 °C) and accelerated storage (25 ± 2 °C and 60 ± 5 % RH) conditions for at least 6 months. The microparticles behaved as a sustained release system both in vitro and in vivo compared to non-encapsulated rivastigmine. The IM administration of the formulation in rats did not produce significant tissue damage. However, it is necessary to reproduce the experiments with multiple doses to rule out a negative effect in terms of tolerability in chronic treatment. To the best of our knowledge, this study is the only one that has obtained the sustained release of rivastigmine from PLGA microparticles after IM administration in an in vivo model.

Fabrication of PLGA Nanoparticles Using Combination of PCL-PVA-PEG Copolymer as Surfactant: In-Vitro Characterization and Cytotoxicity Study

Objective: The present study aimed to fabricate Poly lactic acid co-glycolic acid (PLGA) nanoparticles loaded with resveratrol using a novel graft co-polymer surfactant named Soluplus®. Methods: The PLGA nanoparticles were prepared in the present study using polyvinyl caprolactam polyvinyl acetate polyethylene glycol amphiphilic graft copolymer named Soluplus® as surfactant through double emulsification and single emulsification-solvent evaporation method. The formulations were prepared successfully to encapsulate the drug resveratrol, and then evaluated for their particle size, polydispersity index, zeta potential, drug loading and the degree of entrapment of the drug. A scanning electron microscope was used to examine the morphology of the nanoparticles. In vitro drug release was assessed and, mathematical pharmacokinetic modelling was done to assess the release pattern. A comparative cytotoxicity study between free drug and prepared nanoparticles using MTT assay was carried out for cell viability evaluation. Uptake and internalization of nanoparticles were also studied using confocal fluorescence microscopy. Results: The results demonstrated successful fabrication of the PLGA nanoparticles using the Soluplus as polymer surfactant. The drug, polymer and the all the excipients were found to be compatible and did not indicate any interaction. The results also indicated the prepared nanoparticles (SF2) as suitable resveratrol delivery vehicle in terms of the compliant particle size (344.6 ±6.63 nm), polydispersity index (0.962), zeta potential (- 18.5±1.21), drug loading (18.94± 0.27%), the entrapment efficiency (39.62±0.17%) and drug release (75.13±0.17%). The shape and surface morphology of the formulated nanoparticles were found to be spherical and smooth. Cytotoxicity study also demonstrated significant reduction of cell viability by the nanoparticle compared to free resveratrol. The highest cytotoxicity of SF2 against MCF7 cell was found in 2000 nM concentration with 3.03±0.05 percent of cell viability. It was found that the percentage of growth inhibition was increasing with increasing concentration of SF2 and IC50 value of this assay was 108.94 μg/ml. Conclusion: It has been found that the Resveratrol loaded PLGA nanoparticles were successfully formulated and found to perform better in terms of efficacy and cytotoxicity.

Evaluation of Drug Release Profiles of Titanium Plates Coated with PLGA or Chitosan with Meropenem Using UPLC: An In Vitro Study

In some cases, titanium plates could be a reservoir for harboring bacteria resulting in challenging cases of infection. Current estimates indicate that 10–12% of plates require removal due to infection, exposure, pain, and discomfort. The present investigation was conducted to evaluate the potential sustained meropenem-coated plates amalgamated with “PLGA” polylactic co-glycolic acid and chitosan polymers with the concurrent sterilization effect of gamma irradiation. After coating the plates with either M “meropenem”, MP “meropenem-PLGA, or MC “meropenem-chitosan”, they were divided into two groups of sterile and non-sterile coated plates. The drug release was studied over three-time intervals of 1, 3, and 7 days using ultrahigh-performance liquid chromatography. Overall, the three materials had similar drug release on day one, both in sterile and non-sterile groups, while on days 3 and 7, a noticeable increase in the drug release was perceived in favor of MP. At the same time, no statistically significant difference was observed between sterile and non-sterile groups. A statistically significant increase in drug release was observed between and within the materials over time, with no overall difference between sterile and non-sterile groups.

The Sustained-released Polylactic Co-glycolic Acid Nanoparticles Loaded with Chlorhexidine as Antibacterial Agents Inside the Dental Implant Fixture.

Titanium-based implants are widely used due to their good biocompatibility and high corrosion resistance. Infections after implant placement are the main reason for the failure of implant treatment. Some recent studies have also shown that microbial contamination can occur at the implant-abutment level in implants with healthy or diseased surrounding tissue. The purpose of this study is to investigate the antibacterial effect of slow-release nanoparticles of polylactic co-glycolic acid (PLGA) loaded with chlorhexidine (CHX) inside the implant fixture. Thirty-six implants in three groups were examined in the bacterial culture environment. In the first group, PLGA/CHX nanoparticles; in the second group, the negative control group (distilled water) and in the third group, the positive control groups (chlorhexidine) were used. The bacterial suspensions, including Escherichia coli ATCC: 25922, Staphylococcus aureus ATCC: 6538 and Enterococcus faecalis ATCC: 29212 were used to investigate the antimicrobial effect of the prepared nanoparticles. The results showed that the use of PLGA/CHX nanoparticles significantly inhibited the growth of all three bacteria. Nanoparticles loaded with chlorhexidine had a significant decrease in the growth rate of all three bacteria compared to chlorhexidine and water. The lowest bacterial growth rate was observed in the Enterococcus faecalis/PLGA nanoparticles group, and the highest bacterial growth rate was observed in the Staphylococcus aureus/H2O group. The current study showed that the use of PLGA/CHX nanoparticles could significantly inhibit the growth of all three bacteria. Of course, the current study was conducted in vitro, and to obtain clinical results, we need to conduct a study on human samples. In addition, the results of this study showed that the chemical antimicrobial materials could be used in low concentrations and in a sustained- released manner in cases of dealing with bacterial infections, which can lead to better and targeted performance as well as reduce possible side effects.

Fabrication, bacteriostasis and osteointegration properties researches of the additively-manufactured porous tantalum scaffolds loading vancomycin.

Infected bone defects (IBDs) remains a challenging problem for orthopedists. Clinically, routine management for IBDs has two stages: debridement and systematic antibiotics administration to control infection, and secondary grafting to repair bone defects. Whereas the efficacy is not satisfactory, because the overuse of antibiotics may lead to systemic toxicity, and the emergence of drug-resistant bacteria, as well as the secondary surgery would cause additional trauma and economic burden to the patients. Therefore, it is imperative to develop a novel scaffold for one-stage repair of IBDs. In this study, vancomycin (Van) was encapsulated into poly(lactic co-glycolic acid) (PLGA) microspheres through the double emulsion method, which were then loaded into the additively-manufactured porous tantalum (AM-Ta) through gelatin methacryloyl (GelMA) hydrogel to produce the composite Ta/GelMA hydrogel (Gel)/PLGA/vancomycin(Van) scaffolds for repairing IBDs. Physiochemical characterization of the newly-developed scaffold indicated that the releasing duration of Van was over 2 weeks. Biological experiments indicated good biocompatibility of the composite scaffold, as well as bacteriostasis and osteointegration properties, which showed great potential for clinical application. The construction of this novel scaffold would provide new sight into the development of orthopaedic implants, shedding a novel light on the treatment of IBDs.

NMR relaxation and diffusion studies to probe the motional dynamics of risperidone within PLGA microsphere

The present study aims to investigate the motional dynamics of risperidone within polylactic co-glycolic acid (PLGA) microsphere by employing solution state 1H and 19F nuclear magnetic resonance (NMR) measurements. Risperidone, a second-generation fluorinated antipsychotic drug used for the treatment of schizophrenia is commercially marketed as PLGA microsphere formulation resulting in prolonged release of the drug in solution. Although the current trend in the pharmaceutical market is to develop drug formulation with long-acting release (LAR) products, complete physicochemical characterization of such formulations are scarce. Especially the effects of microsphere encapsulation on the motional properties and diffusion behavior of the drugs are not discussed adequately in any of the earlier reports. We therefore, have employed NMR relaxation and diffusion measurements to decipher the interaction of PLGA cavity water with risperidone. A detailed analysis of NMR relaxation rates confirmed the event of encapsulation and the presence of local motion in the non-fluorinated end of risperidone. Further, the relaxation data indicated a significant alteration in 19F chemical shift anisotropy (CSA) and CSA/dipole-dipole (DD) cross-correlated relaxation mechanism and decreased effect of solvent relaxation pointing out reduced water concentration within the microsphere cavity. 1H and 19F diffusion coefficients of risperidone led to the information about hydrodynamic radius of risperidone in free and encapsulated states. Measurement of hydrodynamic radius supported the presence of limited water in PLGA cavity allowing higher translational mobility of risperidone after the encapsulation.

Hierarchically porous calcium phosphate scaffold with degradable PLGA microsphere network

Calcium phosphate cement (CPC) is widely used in orthopedics, dentistry and spine surgery because of its excellent biocompatibility, osteoconductivity, arbitrary shaping and self-setting ability. However, slow degradation rate of CPC decreases its bone regeneration efficacy. Herein, poly (lactic co-glycolic acid) microspheres (PLGAm) and wollastonite (WS) were mixed with CPC powder to prepare CPC composite pastes, and then the composite pastes were perfused into poly (lactic co-glycolic acid) network (PLGAnw) to construct composite bone repair materials. The degradation of PLGAnw generated interconnected macropores with the short side of about 468 μm along horizontal axis and the long side of about 785 μm along longitudinal axis, while PLGAm degradation generated isolated or partially connected relative smaller spherical macropores with the size range of 53–106 μm and 106–150 μm, respectively, which was same with PLGAm; in addition, CPC formed micro/nano pores after hydration, thus constructing in-situ hierarchically porous CPC composite scaffolds. Meanwhile, PLGAnw and PLGAm also significantly promoted the degradation of CPC due to the release of acidic by-products. Therefore, the introduction of PLGA network and microspheres not only can evidently accelerate degradation of CPC, but also in-situ form connected macropores and hierarchically porous after their degradation, which are expected to improve bone repair effect of CPC.