Effect Of PLGA Research Articles

Native PLGA nanoparticles regulate APP metabolism and protect neurons against β-amyloid toxicity: Potential significance in Alzheimer's disease pathology

Biodegradable poly(lactic-co-glycolic acid)(PLGA) nanoparticles have been used extensively in delivering drugs to target tissues due to their excellent biocompatibility. Evidence suggests that PLGA-conjugated drugs/agents can attenuate pathology in cellular/animal models of Alzheimer's disease (AD), which is initiated by increased level/aggregation of amyloid β (Aβ) peptide generated from amyloid precursor protein (APP). The beneficial effects were attributed to conjugated-drugs rather than to PLGA nanoparticles. Interestingly, we recently reported that PLGA without any drug/agent (native PLGA) can suppress Aβ aggregation/toxicity. However, very little is known about the internalization, subcellular localization or effects of PLGA in neurons. In this study, using primary mouse cortical neurons, we first showed that native PLGA is internalized by an energy-mediated clathrin-dependent/-independent pathway and is localized in endosomal-lysosomal-autophagic vesicles. By attenuating internalization, PLGA can protect neurons against Aβ-mediated toxicity. Additionally, PLGA treatment altered expression profiles of certain AD-associated genes and decreased the levels of APP, its cleaved products α-/β-CTFs and Aβ peptides in mouse as well as iPSC-derived neurons from control and AD patients. Collectively, these results suggest that native PLGA not only protects neurons against Aβ-induced toxicity but also influences the expression of AD-related genes/proteins – highlighting PLGA's implication in normal and AD-related pathology.

Formulation and Characterization of Tenofovir Disproxyl Fumerate Nanoparticles prepared by Nanoprecipitation Method

Tenofovir disproxyl fumerate (TDF) is widely used drug in anti HIV treatment. The main disadvantage with TDF is its low bioavailability. To overcome this problem TDF is formulated in to nanoparticles by using nanoprecipitation method. The formulated nanoparticles were in the range of 106.8nm to 516.4nm. The effect of PLGA and TPGS on the formulated nanoparticles were also studied. It is evident that the concentration of PLGA played an important role in the entrapment and drug loading capacity. On the basis of drug loaded and entrapment efficiency the F8 formulation was considered as optimized formulation. Different analytical techniques were used to determine the amount of drug present in the optimized formulation. The optimized formulation (F8) was subjected to different drug release kinetic models and its stability studies were also conducted in accordance with ICH guidelines.

Antifungal and antibiofilm efficacy of cinnamaldehyde-loaded poly(DL-lactide-co-glycolide) (PLGA) nanoparticles against Candida albicans.

Biofilm-associated Candida infections threaten public health and show high mortality. The drugs used in treatment are very limited due to reasons such as toxicity, low efficacy, and drug resistance, and new alternatives are needed. The use of natural products of plant origin in the biofilm management draws attention. CA (cinnamaldehyde, cinnamic aldehyde, or 3-phenyl-2-propenal) is an essential oil component that can also inhibit mold growth and mycotoxin production. However, there are some limitations in its use due to its poor solubility and volatility in water. Recently, the combination of natural components and nanoparticle-based drug delivery systems shows positive results. In this study, the effects of PLGA (poly(DL-lactide-co-glycolide)) nanoparticles arrested with CA (CA-PLGA NPs) on C. albicans planktonic and biofilm forms (prebiofilm and postbiofilm) were investigated. According to the results, the amount of active ingredient loaded in CA-PLGA NPs is much lower than the free CA and a strong antifungal effect was obtained even at this rate. Also, the postbiofilm application is more effective than prebiofilm application. PLGA NPs can also be a useful carrier for other essential oils, and their potential in various antifungal, antibiofilm, and biomedical applications should be investigated.

Structure, degradation, drug release and mechanical properties relationships of iron-based drug eluting scaffolds: The effects of PLGA

The effects of poly(lactic‑co‑glycolic acid) (PLGA) on structure, degradation, drug release and mechanical properties relationships of iron-based drug eluting scaffolds have been studied comprehensively. The porous structure of the iron has been incorporated with the curcumin-loaded PLGA (CP) particles through dipping method to produce CP-coated porous Fe (CP-Fe). The CP-Fe degradation has been escalated with the increase of PLGA composition due to the hydrolysis of PLGA. The degradation of iron substrate triggered the kinetics of curcumin release as there was a direct correlation between the curcumin release rate and the degradation rate of the CP-Fe scaffold. The stiffness of the CP particles and the interfacial interactions developed between the CP coating and iron surface have enhanced scaffolds' mechanical strengths. The curcumin released from the scaffold significantly arrested osteosarcoma cells growth. It is demonstrated that the PLGA played an important role to control the scaffold degradation and curcumin release as well as enhancing the mechanical properties of the drug device as an integrated system for favorable scaffold-based drug design.

The effects of lactate and acid on articular chondrocytes function: Implications for polymeric cartilage scaffold design

Poly (lactic-co-glycolic acid) (PLGA) and poly-l-lactate acid (PLLA) are biodegradable polymers widely utilized as scaffold materials for cartilage tissue engineering. Their acid degradation products have been widely recognized as being detrimental to cell function. However, the biological effects of lactate, rather than lactic acid, on chondrocytes have never been investigated. This is the major focus of this study. The amounts of lactate and the pH value (acid) of the PLGA and PLLA degradation medium were measured. The effects of PLGA and PLLA degradation medium, as well as different lactate concentrations and timing of exposure on chondrocytes proliferation and cartilage-specific matrix synthesis were investigated by various techniques including global gene expression profiling and gene knockdown experiments. It was shown that PLGA and PLLA degradation medium differentially regulated chondrocyte proliferation and matrix synthesis. Acidic pH caused by lactate inhibited chondrocyte proliferation and matrix synthesis. The effect of lactate on chondrocyte matrix synthesis was both time and dose dependent. A lactate concentration of 100mM and exposure duration of 8h significantly enhanced matrix synthesis. Lactate could also inhibit expression of cartilage matrix degradation genes in osteoarthritic chondrocytes, such as the major aggrecanase ADAMTS5, whilst promoting matrix synthesis simultaneously. Pulsed addition of lactate was shown to be more efficient in promoting COL2A1 expression. Global gene expression data and gene knock down experiments demonstrated that lactate promote matrix synthesis through up-regulation of HIF1A. These observed differential biological effects of lactate on chondrocytes would have implications for the future design of polymeric cartilage scaffolds. Statement of SignificanceLactic acid is a widely used substrate for polymers synthesis, PLGA and PLLA in particular. Although physical and biological modifications have been made on these polymers to make them be better cartilage scaffolds, little concern has been given on the biological effect of lactic acid, the main degradation product of these polymers, on chondrocytes. Our finding illustrates the differential biological function of lactate and acid on chondrocytes matrix synthesis. These results can facilitate future design of lactate polymers-based cartilage scaffolds

Thermodynamic phase behaviour of indomethacin/PLGA formulations

In the current study, the phase behaviour of indomethacin and poly(lactic-co-glycolic acid) (PLGA) formulations was investigated as a function of the molecular weight and the copolymer composition of PLGA. The formulations were prepared by ball milling, and the phase behaviour, comprised of the glass-transition temperature of the formulations and the solubility of indomethacin in PLGA, was measured using modulated differential scanning calorimetry (mDSC). The results determined that the solubility of indomethacin in PLGA at room temperature was very low and increased with a corresponding decrease in the molecular weight of PLGA. The copolymer composition of PLGA had a minor effect on the indomethacin solubility. The effect of PLGA’s molecular weight and copolymer composition on the solubility of indomethacin could be modelled using the Perturbed-Chain Statistical Associating Fluid Theory (PC-SAFT) with a high degree of accuracy when compared with the experimental data. The glass-transition temperatures had a negative deviation from the weighted mean of the glass-transition temperatures of the pure substances, which could be described by the Kwei-equation.

Preparation and in vitro evaluation of meloxicam-loaded PLGA nanoparticles on HT-29 human colon adenocarcinoma cells

Context: The inhibitors of cyclooxygenase (COX)-2 play an important role in cancer chemoprevention. Certain COX-2 inhibitors exert antiproliferative and pro-apoptotic effects on cancer cells.Objective: In this study, meloxicam, which is an enolic acid-type preferential COX-2 inhibitor, was encapsulated in poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles (NPs) to maintain local high concentration, and its efficacy was determined.Methods: NPs were prepared by using salting-out and emulsion-evaporation steps. Meloxicam-loaded NP formulations were evaluated with respect to the drug loading, particle size, polydispersity index, zeta potential, drug release rate, and residual poly(vinyl alcohol) (PVA) percentage. The effects of PLGA and PVA molecular weight variations on the physicochemical properties of NPs were investigated. Stability of meloxicam in NPs was assessed over 3 months. COX-2 expressing human colon adenocarcinoma cell line HT-29 was used in cellular uptake and viability assays.Results: NPs had a spherical shape and a negative zeta potential, and their size ranged between 170–231 nm with a lower polydispersity index. NPs prepared with high molecular weight PLGA were shown to be physically stable over three months at 4°C. The increase in molecular weight of the polymer and emulsifier reduced the in vitro release rate of meloxicam from NPs. Meloxicam-loaded NPs showed cytotoxic effects on HT-29 cells markedly at 800 µM. Cancer cells had high uptake of coumarin-6-loaded NPs.Conclusion: The PLGA NPs developed in this study can be a potentially effective drug delivery system of meloxicam for the treatment of colon cancer.

Composition–property relationships for an experimental composite nerve guidance conduit: evaluating cytotoxicity and initial tensile strength

The objective of this work was to examine the main (individual), combined (interaction) and second-order (quadratic) effects of: (i) poly(D,L-lactide-co-glycolide) (PLGA), (ii) F127, and (iii) a zinc-silicate based bioactive glass, on the cytotoxicity and ultimate tensile strength of an experimental nerve guidance conduit (NGC). The experimental plan was carried out according to a Box-Behnken design matrix. The effects of each compositional factor were quantified using response surface methodology (RSM) techniques. Linear and quadratic polynomial equations were developed to examine cytotoxicity (after incubation at 3, 7 and 28 days) and initial ultimate tensile strength (UTS(0)). Multiple regression analyses showed that the developed models yielded a good prediction for each response examined. It was observed that the beneficial effects of PLGA and bioactive glass on controlling cytotoxicity appeared greater than that of F127. Furthermore, the experimental conduits (with the exception of CNGC-I and CNGC-K) generally showed superior cytocompatibility when compared with the comparable literature for the clinically used nerve guidance conduit Neurolac(®). In this investigation, optimal compositions for cell viability were obtained for the following composition: PLGA = 18.89 wt%/F127 = 0.52 wt%/glass = 12.71 wt%. The optimization of composition with respect to ultimate tensile strength was also established (desired UTS(0) being based on the properties of the control device Neurolac(®) whose UTS is c.20 MPa). The desired UTS(0) of ≤ 20 MPa was found for the composition: PLGA = 18.63 wt%/F127 = 0.77 wt%/glass = 5.54 wt%. A UTS(0) ≤ 30 MPa was recorded for the composition: PLGA = 18.34 wt%/F127 = 0.62 wt%/glass = 9.83 wt%, such tensile strengths are comparable to, reported values for Neurolac(®). Examination of the composition-property relationships with respect to combining cell viability and UTS(0) indicated preferred compositions in the range 17.97-19.90 wt% PLGA, 0.16-1.13 wt% F127 and between 5.54 and ≤ 20 wt% glass. This research demonstrates the value of a design of experiments approach for the design of novel nerve guidance conduits, and shows that the materials examined may have potential for the repair of peripheral nerve discontinuities.

Effects of poly(lactic-co-glycolic acid) on preparation and characteristics of plasmid DNA-loaded solid lipid nanoparticles

Poly(lactic-co-glycolic acid) (PLGA) was used as a polymeric emulsifier to encapsulate plasmid DNA into hydrogenated castor oil (HCO)-solid lipid nanoparticles (SLN) by w/o/w double emulsion and solvent evaporation techniques. The effects of PLGA on the preparation, characteristics and transfection efficiency of DNA-loaded SLN were studied. The results showed that PLGA was essential to form the primary w/o emulsion and the stability of the emulsion was enhanced with the increase of PLGA content. DNA-loaded SLN were spherical with smooth surfaces. The SLN had a negative charge in weak acid and alkaline environment but acquired a positive charge in acidic pH and the cationisation capacity of the SLN increased with the increase of PLGA/HCO ratio. Agarose gel electrophoresis demonstrated that the majority of the DNA maintained its structural integrity after preparation and being extracted or released from DNA-loaded SLN. When PLGA/HCO ratio increased from 5 to 15%, the encapsulation efficiency, loading capacity and transfection efficiency of the nanoparticles increased significantly, whereas the changes of particle size and polydispersity index were insignificant. Cytotoxicity study in cell culture demonstrated that the SLN was not toxic.

Effects of poly (lactic-co-glycolic acid) as a co-emulsifier on the preparation and hypoglycaemic activity of insulin-loaded solid lipid nanoparticles

Poly (lactic-co-glycolic acid) (PLGA) was used as a co-emulsifier in the preparation of insulin-loaded solid lipid nanoparticles (SLN) with hydrogenated castor oil as lipid matrix and lecithin as surfactant by double-emulsion technique. The effects of PLGA on the preparation and hypoglycaemic activity of insulin-loaded SLN were studied. The results showed that with the supplement of PLGA, the encapsulation efficiency and loading capacity were increased significantly from 79.08 +/- 1.62 to 85.57 +/- 3.21% and 1.58 +/- 0.03 to 1.71 +/- 0.06%, whereas the surface charge and particle size were changed insignificantly from -25.87 +/- 2.65 to -22.67 +/- 1.19 mv and 431.0 +/- 16.1 to 397.0 +/- 68.0 nm, respectively. In vivo studies demonstrated that PLGA increased the sustained hypoglycaemic activity from 12 to 36 h and 24 to 120 h in normal and steptozotocin-induced diabetic mice after a single intramuscular injection of the insulin-loaded SLN. These results demonstrated that PLGA could enhance the entrapment of insulin in the nanoparticles, and more importantly, prolong the time of hypoglycaemic activity of the insulin-loaded SLN.