Polylactic Glycolic Acid Research Articles

Sustained release system of paclitaxel based on composite nanofibers for inhibiting renal clear cell carcinoma

The recurrence and metastasis of renal cell carcinoma are severe challenges in clinical treatment. At present, it is urgent to find a strategy to solve this problem and improve the therapeutic effect. In this study, we designed a programmed release system of anticancer drugs by preparing a nanofiber system with two kinds of diameters and biomaterials (polylactic acid-glycolic acid (PLGA) and silk protein) as drug carriers (paclitaxel), which inspired the occurrence and pathological microenvironment of renal cell carcinoma. The controlled degradation of PLGA nanofibers as a drug carrier achieved the short-term release of paclitaxel, which could rapidly inhibit the spread and metastasis of renal cancer, while the silk protein nanofibers as a drug carrier with slow degradation could provide the long time and continuous release of paclitaxel to prevent the proliferation of renal cancer cells and inhibit recurrence. The synergistic effect of the sustained release system of paclitaxel successfully achieved inhibition of the recurrence and metastasis of renal cell carcinoma and improve the therapeutic effect of renal cell carcinoma. The paclitaxel release profile showed that the PLGA nanofiber drug system provided controlled release of paclitaxel in the first 14 days, while the silk protein nanofiber system provided a relatively stable and long-duration release of paclitaxel (1 month). In vitro experiments showed that the sustained release system of paclitaxel had a lasting inhibitory effect on the proliferation of renal clear cell carcinoma cells. These results indicated that the sustained release system of paclitaxel could be used as a promising drug delivery system with highly efficient implementations to reduce the frequency of systemic administration and inhibit tumor growth and recurrence, which could provide a new strategy for the clinical applications in renal cell carcinoma microenvironment.

Effect of methoxy-polyethylene glycol-polylactic acid-bone protective protein nano micelle complex on osteoprotegerin and bone mineral density in osteoporotic rats

This study assessed the effect of nanomicelle complex Methoxy-polyethylene glycol Polylactic acid bone protective protein on OPG and bone mineral density in osteoporotic rats. 35 rats were assigned into group A, B, C, D and E. Except for group A, Osteoarthritis (OA) rat models were established in all other groups. After modeling, group C, D and E were injected with PEG+OPG plasmid, PLL+OPG plasmid and PEG-PLL+ plasmid at 40 mg/kg dose of nanoparticles into mice via tail vein. The other groups were injected with an equal volume of NaCl solution to observe the bone density and OPG level. The bone trabeculae in the femoral tissues of group A were mostly plate-shaped and dense and uniform. Group B bones were sparse without new bone, while the trabecular bone in group C increased, the gap among trabecular bones decreased. The number of trabecular bones increased in group D, and new bone trabecula from group E increased, and arrangement was neat. Bone mineral density (BMD) and BMc levels in the femoral tissue from rats in group B decreased relative to group A (P <0.05), and the levels of BMD and BMc in the femoral tissue from rats in group C increased (P <0.05). BMD and BMc from mouse femur tissue were lower than group E (P <0.05). Moreover, Group B had a lower maximum load than group A (P <0.05) and group E was higher than group D (P <0.05). The femoral tissue structure of rats in group A was complete and bone matrix was arranged well without cavities. The number of bone cells in group B was reduced, while the bone matrix was disorderly distributed, and bones were fractured and more cavities were formed. Compared with group B, groups C, and D, and E had increased bone cells number and reduced bone matrix disorder improvement voids. Immunohistochemistry showed that, OPG increased in group B, and RANKL decreased (P <0.05), which was different from group A (P <0.05). OPG protein and mRNA from C, D and E groups decreased, and RANKL levels increased (P <0.05). PEG-PLL-OPG (PPO) significantly improved OP rat bone mineral density via regulation of BMD, BMc and biomechanical indicators, and the mechanism is related to increased OPG expression and reduced RANKL activity.

A Coarse-Grained Molecular Dynamics Description of Docetaxel-Conjugate Release from PLGA Matrices.

Despite the extensive use of poly-lactic-glycolic-acid (PLGA) in biomedical applications, computational research on the mesoscopic characterization of PLGA-based delivery systems is limited. In this study, a computational model for PLGA is proposed, developed, and validated for the reproducibility of transport properties that can influence drug release, the rate of which remains difficult to control. For computational efficiency, coarse-grained (CG) models of the molecular components under consideration were built using the MARTINI force field version 2.2. The translocation free energy barrier ΔGt* across the PLGA matrix in the aqueous phase of docetaxel and derivatives of varying sizes and solubilities was predicted via molecular dynamics (MD) simulations and compared with experimental release data. The thermodynamic quantity ΔGt* anticipates and can help explain the release kinetics of hydrophobic compounds from the PLGA matrix, albeit within the limit of a drug concentration below a critical aggregation concentration. The proposed computational framework would allow one to predict the pharmacological behavior of polymeric implants loaded with a variety of payloads under different conditions, limiting the experimental workload and associated costs.

Oral delivery of chitosan-coated PLGA nanoemulsion loaded with artesunate alleviates ulcerative colitis in mice

Artesunate (ARS) has been shown to have a protective effect on ulcerative colitis (UC) in mice. However, its lack of targeting and short half-life severely hamper its efficacy. In this study, polylactic acid-glycolic acid copolymer (PLGA) and chitosan (CS) double emulsification solvent volatilisation method was used to prepare a stable nanoemulsion loaded with ARS (CPA). The in vitro drug release profile was detected using dialysis and the potential protective effect was evaluated in an experimental ulcerative colitis (UC) model induced by oral administration of dextran sulphate sodium (DSS). The results suggested that the mean droplet diameter of CPA nanoemulsion is 409.9 ± 9.21 nm, the polydispersity index is 0.17 ± 0.01 and the zeta potential is 40.07 ± 1.65 mV. The cumulative release curve showed the ARS was mainly released at pH 7.4, which is similar to the colonic environment. Oral administration of CPA effectively relieved DSS-induced clinical symptoms by lowering the body weight loss, disease activity index (DAI) score and impressively maintained tight junction protein expression in colon tissue when compared to the blank nanoemulsion control. Meanwhile, CPA remarkably suppressed TLR4/NF-κB pathway activation and mRNA levels of proinflammatory cytokines (IL-1β, IL-6, and TNF-α) while enhanced levels of IL-10 and CD206. In addition, the effect of CPA was slightly better than that of injecting ARS. Therefore, this study demonstrates a convenient drug delivery system for oral administration of ARS that potentially helps to target colonic tissue and alleviate UC.

Microsphere-Gel Composite System with Mesenchymal Stem Cell Recruitment, Antibacterial, and Immunomodulatory Properties Promote Bone Regeneration via Sequential Release of LL37 and W9 Peptides.

Various types of biomaterials have been widely used to treat complex bone defects. However, potential infection risks and inappropriate host immune responses induced by biomaterials can adversely affect the final bone repair outcome. Therefore, the development of novel bone biomaterials with antibacterial and immunomodulatory capabilities is conducive to achieving a good interaction between the host and material, thereby creating a local microenvironment favorable for osteogenesis and ultimately accelerating bone regeneration. In this study, we fabricated a porcine small intestinal submucosa (SIS) hydrogel containing LL37 peptides and polylactic-glycolic acid (PLGA) microspheres encapsulated with WP9QY(W9) peptide (LL37-W9/PLGA-SIS), which can fill irregular bone defects and exhibits excellent mechanical properties. In vitro experiments showed that the microsphere-gel composite system had sequential drug release characteristics. The LL37 peptide released first had good antibacterial performance and BMSC recruitment ability, which could prevent infection at an early stage and increase the number of BMSCs at the injured site. In addition, it also has immunomodulatory properties, showing both pro-inflammatory and anti-inflammatory activities, but its early pro-inflammatory properties are more inclined to activate the M1 phenotype of macrophages. Moreover, the subsequently released W9 peptide not only reduced the expression of pro-inflammatory genes to alleviate inflammation and induced more macrophages to convert to M2 phenotypes but also promoted the osteogenic differentiation of BMSCs. This finely regulated immune response is considered to be more closely related to the physiological bone healing process. When studying the interaction between macrophages and BMSCs mediated by the material, it was found that the immunomodulatory and osteogenic effects were enhanced. In vivo experiments, we constructed rat skull defect models, which further proved that LL37-W9/PLGA-SIS gel can properly regulate the immune response, and has a good ability to promote osteogenesis in situ. In conclusion, the LL37-W9/PLGA-SIS hydrogel has great application prospects in immune regulation and bone therapy.

Value of 3D Printed PLGA Scaffolds for Cartilage Defects in Terms of Repair.

Objective To examine the poly (lactic-co-glycolic acid) and sodium alginate (SA) scaffolds produced by 3D printing technology, access the healing morphology of bones following PLGA/SA implantation within rat cartilage, and examine osteogenesis-related factors in rat serum to determine the efficacy of PLGA/SA scaffolds in healing animal cartilage injuries. To identify the potential of this material to repair a tissue engineering osteochondral injury. Methods Polylactic acid-glycolic acid copolymer and sodium alginate were used as raw materials to create PLGA/SA scaffolds. We observed the scaffold's macrostructure and microstructure, and the scaffold's microstructure was observed through a scanning electron microscope (SEM). The mechanical toughness of a stent was assessed using a biomechanical device. Hematoxylin-eosin staining revealed immune rejection after embedding the scaffolds under the skin of SD rats. The CCK-8 cell proliferation test kit was used to measure cell proliferation. An experimental model of cartilage injury in the knee joint was created in rats. Rats were used to establish an experimental model of cartilage damage in the knee joint. 120 female rats aged 5 weeks were chosen at random from the pool and divided into the experimental and control groups. They were all completely anesthetized with an anesthetic before having the lateral skin of the knee articular cartilage incised. Implanted PLGA/SA scaffolds were not used in the control group and only in the experiment group. Both groups of rats had their muscles and skin sutured and covered in plaster bandages. On the third, seventh, fourteenth, twenty-first, twenty-eighth, and thirty-fifth days after the procedure, the two groups of rats were divided into groups. At various stages, bone tissue, blood samples, and cartilage were examined and evaluated. Immunohistochemistry was used to identify the local bone morphogenetic protein-2 (BMP2). Results (1) PLGA/SA was successfully used to build an artificial cartilage scaffold. (2) Macroscopic and SEM observation results showed the material had increased density and numerous microvoids on the surface. (3) The result of the biomechanical test showed that the PLGA/SA scaffold had superior biomechanical characteristics. (4) The stent did not exhibit any noticeable immunological rejection, according to the results of the subcutaneous embedding experiment performed on rats. (5) The CCK-8 data demonstrated that as the cell development time rose, the number of cells gradually increased. However, there was not statistically significant difference between the growth of the cells in the scaffold extract and the control group (P > 0.05). (6) A successful rat model based on a cartilage defect of the medial knee joint has been built. (7) Observations of specimens revealed that the experimental group's bone tissue score was higher than that of the control group. (8) Using immunohistochemistry, it was found that the experimental group's BMP2 expression was higher on the 7th, 14th, and 28th days than it was in the control group (P < 0.05). Conclusion Strong mechanical and biological properties are present in stable, biodegradable PLGA/SA scaffolds that mimic cartilage. We demonstrated that the cartilage biomimetic PLGA/SA scaffold may repair cartilage and prevent negative reactions such as osteoarthritis in rat knee cartilage, making it suitable as a cartilage scaffolding material for tissue engineering. The PLGA/SA scaffold was also able to promote BMP2 expression in the bone healing zone when inserted into a knee cartilage lesion. Improved cartilage damage is the outcome of BMP2's promotion of bone formation and restriction of bone resorption in the bone healing zone.

Application of Mesoporous Silica Nanoparticle-Chitosan-Loaded BMP-2 in the Repair of Bone Defect in Chronic Osteomyelitis

In order to test the effectiveness of nanoparticle- (NP-) loaded bone morphogenetic protein 2 (BMP-2) in chronic osteomyelitis (CO) complicated with bone defect, a new nanodrug delivery system composed of mesoporous silica NP (MSN) and chitosan were used to load BMP-2 and transfer it to the target region. Bone marrow mesenchymal stem cells (BMSCs) were purchased and cultivated to detect the osteogenesis of chitosan-MSN (Chi-MSN) and polylactic acid glycolic acid (PLGA) delivery system. In addition, the osteogenesis of Chi-MSN was further determined by constructing a bone defect mouse model. In physicochemical property test, we found Chi-MSN NPs could effectively maintain stability in vivo and had pH response characteristics. As a result, the release efficiency of dexamethasone (Dex) and BMP-2 in the environment with pH 7.4 was less, while it increased significantly in pH 6, so as to reduce the BMP-2 and Dex loss during transportation in vivo. Otherwise, we found that the permeation efficiency of Chi-MSN was significantly higher than that of PLGA delivery system, so as to effectively transport BMP-2 and Dex to action target. In the BMSC test, we found that Chi-MSN could better promote their activity and osteogenesis, and the expression of osteogenesis-related genes (runt-related transcription factor 2 (RUNX-2), osteopontine (OPN), alkaline phosphatase (ALP), and osteopontine (OCN)) in the Chi-MSN group was higher. In the bone defect mouse model test, we also found obviously increased bone trabecula number and thickness by Chi-MSN, contributing to better repair of bone defects. Therefore, BMP-2@Chi-MSN may be a better choice for the therapy of CO complicated with bone defect in the future.

Construction and Evaluation of Small-Diameter Bioartificial Arteries Based on a Combined-Mold Technology.

Arterial stenosis or blockage is the leading cause of cardiovascular disease, and the common solution is to substitute the arteries by autologous veins or bypass the blood vessels physically. With the development of science and technology, arteries with diameter larger than 6 mm can be substituted by unbiodegradable polymers, such as polytetrafluoroethylene, clinically. Nevertheless, the construction of a small-diameter (less than 6 mm) artery with living cells has always been a thorny problem. In this study, a suit of combined mold was designed and forged for constructing small-diameter arterial vessels. Based on this combined mold, bioactive arterial vessels containing adipose-derived stem cells (ASCs) and different growth factors (GFs) were assembled together to mimic the inner and middle layers of the natural arteries. Before assembling, ASCs and GFs were loaded into a gelatin/alginate hydrogel. To enhance the mechanical property of the bilayer arterial vessels, polylactic–glycolic acid (PLGA) was applied on the surface of the bilayer vessels to form the outer third layer. The biocompatibility, morphology and mechanical property of the constructed triple-layer arterial vessels were characterized. The morphological results manifested that cells grow well in the gelatin/alginate hydrogels, and ASCs were differentiated into endothelial cells (ECs) and smooth muscle cells (SMCs), respectively. In addition, under the action of shear stress produced by the flow of the culture medium, cells in the hydrogels with high density were connected to each other, similar to the natural vascular endothelial tissues (i.e., endothelia). Especially, the mechanical property of the triple-layer arterial vessels can well meet the anti-stress requirements as human blood vessels. In a word, a small-diameter arterial vessel was successfully constructed through the combined mold and has a promising application prospect as a clinical small-diameter vessel graft.

A novel nanosponge-hydrogel system-based electrochemiluminescence biosensor for uric acid detection.

In this work, a highly efficient electrochemiluminescence (ECL) biosensor was developed based on the nanosponge-hydrogel system for uric acid (UA) detection. First, the nanosponge consisted of polylactic acid glycolic acid (PLGA) nanoparticles immobilized with MoS2 quantum dots (QDs) and urate oxidase (UAO). The marked loading capability of PLGA nanoparticles enables loading many biomolecules and QDs for the specific recognition of UA. Urate oxidase on the nanosponge can catalyze UA to generate H2 O2 in situ, which further triggers the ECL signal for the MoS2 QDs. Furthermore, the biocompatible acrylamide-based hydrogel not only effectively retained the functionalities of the chimeric nanosponge-hydrogel, but also provided structural integrity and engineering flexibility on the electrode for ECL sensing applications. In addition, there were many ester groups and amide bonds in the nanosponge-hydrogel structure. Therefore, many electron can be excited in the ECL process due to the large number of lone electron pairs on oxygen and nitrogen atoms. This resulted in a seven-fold ECL enhancement of the MoS2 QDs. Finally, the nanosponge-hydrogel structure-based ECL biosensor was successfully used in real clinical serum assays. This showed a good analytical performance for UA detection (100-500 μmol/L) with a limit of detection of 20 μmol/L.

Customized Design 3D Printed PLGA/Calcium Sulfate Scaffold Enhances Mechanical and Biological Properties for Bone Regeneration

Polylactic glycolic acid copolymer (PLGA) has been widely used in tissue engineering due to its good biocompatibility and degradation properties. However, the mismatched mechanical and unsatisfactory biological properties of PLGA limit further application in bone tissue engineering. Calcium sulfate (CaSO4) is one of the most promising bone repair materials due to its non-immunogenicity, well biocompatibility, and excellent bone conductivity. In this study, aiming at the shortcomings of activity-lack and low mechanical of PLGA in bone tissue engineering, customized-designed 3D porous PLGA/CaSO4 scaffolds were prepared by 3D printing. We first studied the physical properties of PLGA/CaSO4 scaffolds and the results showed that CaSO4 improved the mechanical properties of PLGA scaffolds. In vitro experiments showed that PLGA/CaSO4 scaffold exhibited good biocompatibility. Moreover, the addition of CaSO4 could significantly improve the migration and osteogenic differentiation of MC3T3-E1 cells in the PLGA/CaSO4 scaffolds, and the PLGA/CaSO4 scaffolds made with 20 wt.% CaSO4 exhibited the best osteogenesis properties. Therefore, calcium sulfate was added to PLGA could lead to customized 3D printed scaffolds for enhanced mechanical properties and biological properties. The customized 3D-printed PLGA/CaSO4 scaffold shows great potential for precisely repairing irregular load-bearing bone defects.

Abstract 5406: Novel quatramer nano-formulation of dual-targeted PI3-Kδ/HDAC6 inhibitor, HSB-510, suppresses growth of triple negative breast cancer

Abstract Triple negative breast cancer (TNBC) is an aggressive subtype with limited treatment options and a worse clinical outcome as compared with other breast cancer subtypes. Multiple studies have shown that progression of TNBC depends on more than one signalling pathways, suggesting that the therapies with multi-targeted anti-cancer agents will offer improved therapeutic benefit through synergistic effects in inhibiting cancer growth. Dual-targeted inhibitors of phosphoinositide 3-kinase (PI3-K) and histone deacetylase (HDAC) have emerged as promising cancer therapy candidates. However, poor aqueous solubility and bioavailability limited their efficacy in cancer and accordingly, improved delivery systems are needed. The present studies have investigated the encapsulation of PI3-Kδ/HDAC6 dual inhibitor into hybrid block co-polymers (polylactic acid-methoxy polyethylene glycol; polylactic acid-polyethylene glycol-polypropylene glycol-polyethylene glycol-polylactic acid) (HSB-510) as a delivery system to target PI3-Kδ and HDAC6 pathways in TNBC cells. The prepared HSB-510 Quatramer nano-formulation showed an average diameter of 96 ±3 nm, the zeta potential of -17±2 mV, and PDI of ˂0.1 with a slow and sustained release profile of PI3-Kδ/HDAC6 inhibitors in a non-physiological buffer. In vitro studies with HSB-510 have demonstrated substantial growth inhibition of TNBC cell lines, MDA-MB-468, SUM-149 and Ehrlich ascites carcinoma (EAC) as well as downregulation of phospho-AKT, phospho-ERK and c-MYC levels. Importantly, bi-weekly treatment of BALB/c wild-type mice harbouring EAC cells (syngeneic mouse model) with HSB-510 at a dose of 25 mg/kg resulted in significant (76%) tumor growth inhibition (TGI). The treatment with HSB-510 was without any significant effect on the body weights of the mice. These results demonstrate that a novel Quatramer nano-formulation of a novel PI3-Kδ/HDAC6 dual inhibitor (HSB-510) represents an approach for successful targeting of TNBC and potentially other cancer types. Citation Format: Sachchidanand Tiwari, Suiyang Liu, Mohammad Anees, Neha Mehrotra, Ashish Thakur, Gregory Tawa, Gurmit Grewal, Richard M. Stone, Surender M. Kharbanda, Harpal Singh. Novel quatramer nano-formulation of dual-targeted PI3-Kδ/HDAC6 inhibitor, HSB-510, suppresses growth of triple negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5406.

Application of 3D-Printed, PLGA-Based Scaffolds in Bone Tissue Engineering.

Polylactic acid–glycolic acid (PLGA) has been widely used in bone tissue engineering due to its favorable biocompatibility and adjustable biodegradation. 3D printing technology can prepare scaffolds with rich structure and function, and is one of the best methods to obtain scaffolds for bone tissue repair. This review systematically summarizes the research progress of 3D-printed, PLGA-based scaffolds. The properties of the modified components of scaffolds are introduced in detail. The influence of structure and printing method change in printing process is analyzed. The advantages and disadvantages of their applications are illustrated by several examples. Finally, we briefly discuss the limitations and future development direction of current 3D-printed, PLGA-based materials for bone tissue repair.

Fabrication and evaluation of bone morphogenetic protein-2 microspheres coated black phosphorus nanosheets@polylactic-glycolic acid copolymers scaffold: A multifunctional antibacterial photothermal scaffold for bone regeneration

Clinical bone defects are often caused by high energy injury and are easily complicated by bacterial infection. An ideal bone repair material should promote bone regeneration and prevent bacterial infection. In this study, a multifunctional photothermal scaffold was developed: bone morphogenetic protein-2 (BMP-2)/polylactic-glycolic acid copolymers (PLGA) microspheres were prepared by a double emulsion method and then coated on the scaffolds prepared using a mixture of black phosphorus nanosheets (BPs) and PLGA, to form BMP-2@BPs scaffolds. The structural and photothermal properties of the composite scaffolds were characterized. The BMP-2@BPs scaffolds demonstrated good biocompatibility in both in vitro and in vivo experiments. The BMP-2@BPs scaffolds promoted osteogenic differentiation through a combination of BMP-2 release and upregulation of the expression of heat shock proteins by the radiation of near-infrared (NIR) light, which further upregulated the expression of osteogenesis-related genes. In addition, BPs demonstrated antibacterial effects under the mediation of NIR, which is beneficial for the prevention of clinical bacterial infections. In summary, the BMP-2@BPs scaffold was a multifunctional photothermal scaffold that could accelerate bone regeneration and act against bacteria. This study provides a new perspective for the treatment of bone defects and infectious bone defects.

Sorafenib-Loaded PLGA-TPGS Nanosystems Enhance Hepatocellular Carcinoma Therapy Through Reversing P-Glycoprotein-Mediated Multidrug Resistance.

Multidrug resistance (MDR) is a key determinant for hepatocellular carcinoma chemotherapy failure. P-glycoprotein is one of the main causes of MDR by causing drug efflux in tumor cells. In order to solve this thorny problem, we prepared a sorafenib-loaded polylactic acid-glycolic acid (PLGA) - D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) nanoparticles (SPTNs). SPTNs were successfully synthesized through an ultrasonic emulsion solvent evaporation method with a favourable encapsulation efficiency of 90.35%. SPTNs were almost spherical in shape with uniform particle size (215.70 ± 0.36 nm), narrow polydispersity index (0.27 ± 0.02) and negative surface charge (-26.01 ± 0.65 mV). In the cellular uptake assay, the intracellular coumarin-6 (C6) fluorescence of TPGS component-based PLGA nanoparticles (C6-PTNs) was 1.63-fold higher relative to that of PVA component-based PLGA nanoparticles (C6-PVNs). The half-maximal inhibitory concentration and apoptosis ratio of SPTNs against HepG2/MDR cells were 3.90 μM and 75.62%, respectively, which were notably higher than free SF and sorafenib-PLGA-PVA nanoparticles (SPVNs). The anti-drug efflux activities of SPTNs were assessed by the intracellular trafficking assay using verapamil as a P-gp inhibitor. SPTNs could effectively inhibit the drug efflux in tumor cells detected by flow cytometry, and suppressed relative MDR1 gene as well as P-glycoprotein expression in tumor cells. Attributed to the MDR reversion effect of SPTNs, the in vivo antitumor efficacy experiment showed that SPTNs significantly inhibited the tumor growth of HepG2/MDR xenograft-bearing nude mice, and obviously reduced the toxicity against liver and kidney compared with SF treatment. In summary, SPTNs, as highly efficient and safe antitumor nano delivery systems, showed promising potential for hepatocellular carcinoma therapy through reversing P-glycoprotein-mediated MDR. Graphical Abstract.

Nanofat functionalized injectable super-lubricating microfluidic microspheres for treatment of osteoarthritis

Nanofat (NF) is a fine emulsion that has been used to treat a variety of diseases given its abundance of bioactive components. However, the biological functions of NF have been limited due to its inability to localize during implantation. In this study, NF was immobilized in microfluidic-generated aldehyde-modified polylactic glycolic acid (PLGA) porous microspheres (PMs) via Schiff base condensation and non-covalent binding in a three-dimensional (3D) porous network (PMs@NF). The PMs effectively enhanced the cartilage-targeted retention efficiency of NF, which also resulted in remarkable lubrication performance, with the friction coefficient being reduced by ∼80%, which was maintained over time. Meanwhile, the 3D penetrating structure of the microspheres stimulated cytokine secretion by the NF-derived stem cells, upregulating the expression of anabolism-related genes and downregulating catabolism, and the expression of inflammation-related and pain-related genes. Injecting PMs@NF into the knee joint cavity of a rat model with destabilization of the medial meniscus (DMM) reduced osteophyte formation and protected the cartilage from degeneration, thereby inhibiting the progression of osteoarthritis and improving animal behavior. In summary, this study developed a multifunctional platform with NF immobilization and super-lubrication, which showed great potential for the minimally invasive treatment of osteoarthritis.

Development and evaluation of PLA based hybrid block copolymeric nanoparticles for systemic delivery of pirarubicin as an anti-cancer agent

Pirarubicin (PIRA) is a semi-synthetic anthracycline derivative that is reported to have lesser toxicity and better clinical outcomes as compared to its parental form doxorubicin (DOX). However, long term use of PIRA causes bone marrow suppression and severe cardiotoxicity to the recipients. Herein, we have developed a biodegradable polymeric nano platform consisting of amphiphilic di-block copolymer methoxy polyethylene glycol-polylactic acid and a hydrophobic penta-block copolymer polylactic acid-pluronic L-61-polylactic acid as a hybrid system to prepare PIRA (& DOX) encapsulated nanoparticles (NPs) with an aim to reduce its off targeted toxicity and enhance therapeutic efficacy for cancer therapy. Prepared PIRA/DOX NPs showed uniform particle size distribution, high encapsulation efficiency and sustained drug release profile. Cytotoxicity evaluation of PIRA NPs against TNBC cells and mammospheres showed its superior anti-cancer activity over DOX NPs. Anti-cancer efficacy of PIRA/DOX NPs was found significantly enhanced in presence of penta-block copolymer which confirmed chemo-sensitising ability of pluronic L-61. Most importantly, encapsulation of PIRA/DOX in the NPs reduced their off targeted toxicity and increased the maximum tolerated dose in BALB/c mice. Moreover, treatment of EAC tumor harbouring mice with PIRA NPs resulted in higher tumor regression as compared with the groups treated with free PIRA, free DOX or DOX NPs. Altogether, the results conclude that prepared PIRA NPs exhibits an excellent anti-cancer therapeutic efficacy and has a strong potential for cancer therapy.

LIPID-POLYMER HYBRID NANOCARRIERS AS A NOVEL DRUG DELIVERY PLATFORM

The main aim of my review to discuss the most prominent nanocarrier, “Lipid-Polymer Hybrid Nanoparticle” (LPHNPs) that overcomes the limitation of lipid and polymeric nanoparticles. That consists of polymeric core and lipid outer layer. The polymeric core encapsulates both hydrophilic and hydrophobic drugs and lipid shell provides a coat that gives a barrier to prevent drug leakage and easily penetrate into the skin. The LPHNPs has significant application in drug delivery, drug targeting, cancer treatment, brain drug delivery, multiple drug delivery, delivery of diagnostic imaging agent and Small interfering Ribonucleic acid (siRNA). This session is based on literature information in which LPHNPs were prepared by Two-step and Single-step method. Most of the researcher use the Single-step method by emulsification solvent evaporation and Nanoprecipitation method that are easy to prepare LPHNPs. The Polylactic Glycolic acid (PLGA), Poly € caprolactone, Chitosan, Alginate, Dextron, Sodium Alginate, etc used as polymeric core and Stearic Acid, Palmitic Acid, Cetyl Alcohol, Behenol Alcohol, etc used as lipid core. All results were analyzed by us according to the literature and authors’ expertise. The drug release depends on diffusion processes, followed by erosion, then swelling of the matrix. The lipid shell provides a biocompatible shield that acts as the phospholipid bilayer of skin and easily penetrates into the skin. That also capable to deliver the multidrug and diagnostic imaging agent for the treatment of cancer. The Lipid-Polymer Hybrid Nanoparticles are the most prominent nanocarrier for drug delivery. That is capable to deliver both Hydrophilic and Lipophilic drugs and show high bioavailability.

Indocyanine-type Infrared-820 Encapsulated Polymeric Nanoparticle-Assisted Photothermal Therapy of Cancer.

Organic small-molecule photosensitizers are well-characterized and known for the light-responsive treatment modality including photodynamic therapy. Compared with ultraviolet–visible (UV–vis) light used in conventional photodynamic therapy with organic photosensitizers, near-infrared (NIR) light from 700 to 900 nm is less absorbed and scattered by biological tissue such as hemoglobin, lipids, and water, and thus, the use of NIR excitation can greatly increase the penetration depth and emission. Additionally, NIR light has lower energy than UV–vis that can be beneficial due to less activation of fluorophores present in tissues upon NIR irradiation. However, the low water stability, nonspecific distribution, and short circulation half-life of the organic photosensitizers limit its broad biological application. NIR responsive small-molecule fluorescent agents are the focus of extensive research for combined molecular imaging and hyperthermia. Recently a new class of NIR dye, IR-820 with excitation and emission wavelengths of 710 and 820 nm, has been developed and explored as an alternative platform to overcome some of the limitations of the most commonly used gold nanoparticles for photothermal therapy of cancer. Herein, we synthesized a core–shell biocompatible nanocarrier envelope made up of a phospholipid conjugated with poly(ethylene glycol) as a shell, while poly(lactic glycolic acid) (PLGA) was used as a core to encapsulate IR-820 dye. The IR-820-loaded nanoparticles were prepared by nanoprecipitation and characterized for their physicochemical properties and photothermal efficiency. These nanoparticles were monodispersed and highly stable in physiological pH with the hydrodynamic size of 103 ± 8 nm and polydispersity index of 0.163 ± 0.031. The IR-820-loaded nanocarrier showed excellent biocompatibility in the dark, whereas remarkable phototoxicity was observed with breast cancer cells (MCF-7) upon NIR laser excitation. Therefore, the IR-820-loaded phospholipid mimicking biodegradable lipid-polymer composite nanoparticles could have great potential for cancer theranostics.

Magnetic Nano-Platform Enhanced iPSC-Derived Trabecular Meshwork Delivery and Tracking Efficiency.

PurposeTransplantation of stem cells to remodel the trabecular meshwork (TM) has become a new option for restoring aqueous humor dynamics and intraocular pressure homeostasis in glaucoma. In this study, we aimed to design a nanoparticle to label induced pluripotent stem cell (iPSC)-derived TM and improve the delivery accuracy and in vivo tracking efficiency.MethodsPLGA-SPIO-Cypate (PSC) NPs were designed with polylactic acid-glycolic acid (PLGA) polymers as the backbone, superparamagnetic iron oxide (SPIO) nanoparticles, and near-infrared (NIR) dye cypate. In vitro assessment of cytotoxicity, iron content after NPs labeling, and the dual-model monitor was performed on mouse iPSC-derived TM (miPSC-TM) cells, as well as immortalized and primary human TM cells. Cell function after labeling, the delivery accuracy, in vivo tracking efficiency, and its effect on lowering IOP were evaluated following miPSC-TM transplantation in mice.ResultsInitial in vitro experiments showed that a single-time nanoparticles incubation was sufficient to label iPSC-derived TM and was not related to any change in both cell viability and fate. Subsequent in vivo evaluation revealed that the use of this nanoparticle not only improves the delivery accuracy of the transplanted cells in live animals but also benefits the dual-model tracking in the long term. More importantly, the use of the magnet triggers a temporary enhancement in the effectiveness of cell-based therapy in alleviating the pathologies associated with glaucoma.ConclusionThis study provided a promising approach for enhancing both the delivery and in vivo tracking efficiency of the transplanted cells, which facilitates the clinical translation of stem cell-based therapy for glaucoma.

Mechanism of poly(lactic acid-glycolic acid) (PLGA) copolymer nanoparticles in enhancing cytotoxicity against occurrence and development of lung cancer metastasis

Poly lactic acid-glycolic acid copolymer (PLGA) plays a critical role in inducing tumor cells apoptosis. However, the solubility of the compound itself puts a limit on its use value in treatment of tumor. In this study, we used PLGA combined with nanoparticles as a strategy for metastatic tumor of lung cancer. We evaluated the biological effect of PLGA nanoparticles on enhancing cytotoxicity and its anti-tumor effect against metastasis tumor of lung cancer. Confocal microscope was used to detect the transfection efficiency of tumor cells. PLGA and PLGA-cored nanoparticles (PLGA AC-NPs) were used to interfere with proliferation and apoptosis of metastatic tumor cell line from lung cancer and flow cytometry was used to explore its effect. Furthermore, PLGA and PLGA AC-NPs were injected into the chest of lung cancer mice for treatment. Cell proliferation and apoptosis were detected through measurement of tumor volume, immunohistochemistry (IHC) and Westernblot protein analysis. It was found that, PLGA AC-NPs significantly enhanced cell uptake while PLGA ACNPs regulated tumor by inhibiting cell proliferation and promoting apoptosis. It was also observed in vivo transplanted tumor model that the growth of metastatic tumor of lung cancer was inhibited significantly by NGO-PEG-PEI/Cer, while proliferation and accelerated apoptosis were also slowed down. PLGA AC-NPs can inhibit tumor growth by promoting apoptosis and inhibiting further proliferation of tumor cells.