Poly Lactic-glycolic Acid Nanoparticles Research Articles

Supramolecular Peptide Nanofiber/PLGA Nanocomposites for Enhancing Pulmonary Drug Delivery.

Effective drug delivery to pulmonary sites will benefit from the design and synthesis of novel drug delivery systems that can overcome various tissue and cellular barriers. Cell penetrating peptides (CPPs) have shown promise for intracellular delivery of various imaging probes and therapeutics. Although CPPs improve delivery efficacy to a certain extent, they still lack the scope of engineering to improve the payload capacity and protect the payload from the physiological environment in drug delivery applications. Inspired by recent advances of CPPs and CPP-functionalized nanoparticles, in this work, we demonstrate a novel nanocomposite consisting of fiber-forming supramolecular CPPs that are coated onto polylactic-glycolic acid (PLGA) nanoparticles to enhance pulmonary drug delivery. These nanocomposites show a threefold higher intracellular delivery of nanoparticles in various cells including primary lung epithelial cells, macrophages, and a 10-fold increase in endothelial cells compared to naked PLGA nanoparticles or a twofold increase compared to nanoparticles modified with traditional monomeric CPPs. Cell uptake studies suggest that nanocomposites likely enter cells through mixed macropinocytosis and passive energy-independent mechanisms, which is followed by endosomal escape within 24 h. Nanocomposites also showed potent mucus permeation. More importantly, freeze-drying and nebulizing formulated nanocomposite powder did not affect their physiochemical and biological activity, which further highlights the translative potential for use as a stable drug carrier for pulmonary drug delivery. We expect nanocomposites based on peptide nanofibers, and PLGA nanoparticles can be custom designed to encapsulate and deliver a wide range of therapeutics including nucleic acids, proteins, and small-molecule drugs when employed in inhalable systems to treat various pulmonary diseases.

Chitosan Oleate Coated Poly Lactic-Glycolic Acid (PLGA) Nanoparticles versus Chitosan Oleate Self-Assembled Polymeric Micelles, Loaded with Resveratrol.

Chitosan oleate (CS-OA), a chitosan salt with amphiphilic properties, has demonstrated the ability to self-assemble in aqueous environment to give polymeric micelles useful to load poorly soluble drugs. More recently, CS-OA was proposed to stabilize nanoemulsions during the preparation by emulsification and solvent evaporation of poly lactic-glycolic acid (PLGA) nanoparticles (NPs) loaded with curcumin. Positive mucoadhesive behavior and internalization properties were demonstrated for these NPs attributable to the presence of positive charge at the NP surface. In the present paper, two CS-OA-based nanosystems, micelles and PLGA NPs, were compared with the aim of elucidating their physico-chemical characteristics, and especially their interaction with cell substrates. The two systems were loaded with resveratrol (RSV), a hydrophobic polyphenol endowed with anti-cancerogenic, anti-inflammatory, and heart/brain protective effects, but with low bioavailability mainly due to poor aqueous solubility. Calorimetric analysis and X-ray spectra demonstrated amorphization of RSV, confirming its affinity for hydrophobic domains of polymeric micelles and PLGA core of NPs. TGA decomposition patterns suggest higher stability of PLGA-NPs compared with polymeric micelles, that anyway resulted more stable than expected, considering the RSV release profiles, and the cell line interaction results.

ANTIMICROBIAL POTENTIAL OF HYDROGEL INCORPORATED WITH PLGA NANOPARTICLES OF CROSSANDRA INFUNDIBULIFORMIS

Objective: Present study is aimed at formulation of Hydrogel containing Poly Lactic Glycolic Acid (PLGA) nanoparticles incorporated with ethanolic extract of Crossandra infundibuliformis (EECI) and investigate the efficacy of hydrogel nanoparticles as a carrier of antimicrobial constituents.
 Methods: Poly Lactic Glycolic Acid (PLGA) nanoparticles containing ethanolic extract of Crossandra infundibuliformis (EECI) were synthesized by an emulsion-evaporation method and their physicochemical properties were studied. Polymeric PLGA nanoparticles were then incorporated into gel matrix, using Hydroxy Propyl Methyl Cellulose (HPMC K4M) as a base. The antibacterial activity of nanoparticulated hydrogel formulations were evaluated by agar well diffusion method against Staphylococcus aureus, Bacillus subtilis, Escherichia coli and Pseudomonas aeruginosa.
 Results: Nanoparticulate hydrogel formulations exhibited high viscosity, neutral pH with good spreadability which is appropriate for transdermal application as well as showed prolonged drug release from optimized formulation up to 24 h. Nanoparticulate hydrogel formulations were effective inhibitors of all the micro-organisms with more promising activity against Staphylococcus aureus.
 Conclusion: Nanoparticulate hydrogel formulation can be used as a feasible alternative to conventional formulations of Crossandra infundibuliformis extract with advanced permeation characteristics of antimicrobial constituents for transdermal application.

Chitosan Oleate Salt as an Amphiphilic Polymer for the Surface Modification of Poly-Lactic-Glycolic Acid (PLGA) Nanoparticles. Preliminary Studies of Mucoadhesion and Cell Interaction Properties.

Most of the methods of poly-lactic-glycolic acid (PLGA) preparation involve the passage through the emulsification of a PLGA organic solution in water followed by solvent evaporation or extraction. The choice of the droplet stabilizer during the emulsion step is critical for the dimensions and the surface characteristics of the nanoparticles (NPs). In the present work, a recently described ionic amphiphilic chitosan derivative, chitosan oleate salt (CS-OA), was proposed for the first time to prepare PLGA NPs. A full factorial design was used to understand the effect of some formulation and preparation parameters on the NP dimensions and on encapsulation efficiency (EE%) of Nile red, used as a tracer. On the basis of the DoE study, curcumin loaded NPs were prepared, having 329 ± 42 nm dimensions and 68.75% EE%. The presence of a chitosan coating at the surface was confirmed by positive zeta potential and resulted in mucoadhesion behavior. The expected improvement of the interaction of the chitosan surface modified nanoparticles with cell membrane surface was confirmed in Caco-2 cell culture by the internalization of the loaded curcumin.

In vitro, ex vivo and in vivo characterization of PLGA nanoparticles loading pranoprofen for ocular administration

Pranoprofen (PF) is a NSAID considered as a safe anti-inflammatory treatment for strabismus and/or cataract surgery. The drug has been formulated in poly (lactic/glycolic) acid (PLGA) nanoparticles (PF-F1NPs with cPF 1.5mg/mL, PF-F2NPs with cPF 1mg/mL) produced by solvent displacement technique and tested the in vitro cytotoxicity, ex vivo corneal permeation, in vivo ocular tolerance and in vivo anti-inflammatory efficacy of PF-F1NPs, PF-F2NPs, in comparison to eye drops conventional dosage form (Oftalar®, PF 1mg/mL) and free drug solution (PF dissolved in PBS, 1.5mg/mL). The mean particle size of both formulations was around 350nm, with polydispersity index below 0.1, and a net negative charge of −7.41mV and −8.5mV for PF-F1NPs and PF-F2NPs, respectively. Y-79 human retinoblastoma cell line was used to evaluate the cytotoxicity of PF-F1NPs and PF-F2NPs, which were compared to blank NPs and free drug solution (PF dissolved in PBS, 1.5mg/mL). Concentrations up to 75μg/mL exhibited no toxicity to Y-79 cells, whereas at 150μg/mL a decrease of about 80% on the cell viability was observed after exposing the cells to PF-F1NPs. When treating the Y-79 cells with concentrations of PF-F2NPs between 1μg/mL to 100μg/mL, the cell viability was similar to control values after 24h and 48h of exposure. An ex vivo corneal permeation study was carried out in New Zealand rabbits. A very similar profile has been observed for the permeation of PF through the cornea when administered as eye drops and as free drug solution, which was kept much lower in comparison to PF-NPs formulations. The permeated amount of PF from the PF-F1NPs was slightly smaller than from PF-F2NPs, attributed to the increase of viscosity of the formulations with the increase of cPVA concentration. New Zealand white rabbits were also used to evaluate the irritancy of PF-F1NPs and PF-F2NPs, which demonstrated to be well-tolerated to the eye (i.e. the mean total score (MTS) was 0). PF-F2NPs exhibited the highest QP (amounts of PF permeated in the cornea) and significantly reduced the ocular edema compared to the tested formulations. The QR (amounts of PF retained in the cornea) of the PF-F1NPs was greater than that obtained for PF-F2NPs.

Nanoparticle-Mediated Delivery of Irbesartan Induces Cardioprotection from Myocardial Ischemia-Reperfusion Injury by Antagonizing Monocyte-Mediated Inflammation.

Myocardial ischemia-reperfusion (IR) injury limits the therapeutic effect of early reperfusion therapy for acute myocardial infarction (AMI), in which the recruitment of inflammatory monocytes plays a causative role. Here we develop bioabsorbable poly-lactic/glycolic acid (PLGA) nanoparticles incorporating irbesartan, an angiotensin II type 1 receptor blocker with a peroxisome proliferator-activated receptor (PPAR)γ agonistic effect (irbesartan-NP). In a mouse model of IR injury, intravenous PLGA nanoparticles distribute to the IR myocardium and monocytes in the blood and in the IR heart. Single intravenous treatment at the time of reperfusion with irbesartan-NP (3.0 mg kg−1 irbesartan), but not with control nanoparticles or irbesartan solution (3.0 mg kg−1), inhibits the recruitment of inflammatory monocytes to the IR heart, and reduces the infarct size via PPARγ-dependent anti-inflammatory mechanisms, and ameliorates left ventricular remodeling 21 days after IR. Irbesartan-NP is a novel approach to treat myocardial IR injury in patients with AMI.

Nanoparticle-Mediated Targeting of Cyclosporine A Enhances Cardioprotection Against Ischemia-Reperfusion Injury Through Inhibition of Mitochondrial Permeability Transition Pore Opening.

Myocardial ischemia-reperfusion (IR) injury limits the therapeutic effects of early reperfusion therapy for acute myocardial infarction (MI), in which mitochondrial permeability transition pore (mPTP) opening plays a critical role. Our aim was to determine whether poly-lactic/glycolic acid (PLGA) nanoparticle-mediated mitochondrial targeting of a molecule that inhibits mPTP opening, cyclosporine A (CsA), enhances CsA-induced cardioprotection. In an in vivo murine IR model, intravenously injected PLGA nanoparticles were located at the IR myocardium mitochondria. Treatment with nanoparticles incorporated with CsA (CsA-NP) at the onset of reperfusion enhanced cardioprotection against IR injury by CsA alone (as indicated by the reduced MI size at a lower CsA concentration) through the inhibition of mPTP opening. Left ventricular remodeling was ameliorated 28 days after IR, but the treatment did not affect inflammatory monocyte recruitment to the IR heart. In cultured rat cardiomyocytes in vitro, mitochondrial PLGA nanoparticle-targeting was observed after the addition of hydrogen peroxide, which represents oxidative stress during IR, and was prevented by CsA. CsA-NP can be developed as an effective mPTP opening inhibitor and may protect organs from IR injury.

Surfactant-free Formulation of Poly(Lactic/Glycolic) Acid Nanoparticles Encapsulating Functional Polypeptide: A Technical Note

Therapeutic proteins or polypeptides can be formulated into various particulate delivery systems including the polymeric carriers to avoid rapid degradation and to maintain the sustained release for better therapeutic effects (1). Poly(lactic/glycolic) acid (PLGA) micro/nanoparticle is a widely used formulation agent because of its good biodegradability, biocompatibility, and approved clinical usage, which have been available in the market to treat prostate cancer, acromegaly, periodontal disease, and pediatric growth hormone deficiency (2). The sustaining and complete release of proteins in their native or active forms from the PLGA micro/nanoparticles is often a challenging task (3). Proteins are generally formulated into PLGA nanoparticles by water/oil/water double-emulsion–solvent evaporation method, which generates hydrophilic/hydrophobic interface that may result in the unfolding or denaturing of protein molecules (4). Thus, polymeric surfactants are usually used to lower surface tension of protein solutions and to prevent aggregation of protein molecules at hydrophobic surface (1). Polyvinyl alcohol (PVA) is a widely used polymeric surfactant in the exterior aqueous phase as an emulsifier. However, the safety of PVA still appears to be a concern from the previous literature reports (5,6). Following repeated subcutaneous or intravenous administrations of PVA, various organ lesions and hypertension have been reported in rats, and central nervous system depression and anemia followed by renal damage have also been reported in beagle dogs; whereas, orally administered PVA is relatively harmless in mice or rat (5,6). Therefore, residual PVA was always removed by washing procedures such as repetitive centrifugation (7) or filtration (8), which removes not only the PVA but also the unencapsulated proteins or polypeptides, which might be often valuable or hard to collect. Hence, a few substituting emulsifiers have been studied. For example, poly(ethylene glycol) (PEG) was used successfully as the stabilizer to prepare enzyme-loaded PLGA microparticles (9). Besides, surfactant-free formulation was achieved by nanoprecipitation/solvent-displacement method that would not alter surface properties of PLGA nanoparticles, but this method may suffer the low encapsulation efficiency when low protein concentration solution is to be used (10). In the present study, we introduced another surfactant-free method to prepare PLGA nanoparticles encapsulating polypeptides by double-emulsion–solvent evaporation method. We used sucrose as the stabilizer of the exterior aqueous phase to prevent aggregation of PLGA nanoparticles during formulation process. Nerve growth factor (NGF), a small secreted protein which can induce the differentiation and survival of particular target neurons, was used as the model protein. As sucrose is a nontoxic material, additional washing procedures are not necessarily needed for NGF-loaded PLGA nanoparticles, and thus, the valuable NGF loss can be minimized. The release of functional NGF molecules from these nanoparticles was verified by either the antibody recognition in enzyme-linked immunosorbent assay (ELISA) method or the induction on the neurite outgrowth of PC-12 cells.

Drug Delivery to the Cochlea Using PLGA Nanoparticles

This study aimed to investigate the efficacy of encapsulating therapeutic molecules in poly lactic/glycolic acid (PLGA) nanoparticles for drug delivery to the cochlea. An experimental study. We examined the distribution of rhodamine, a fluorescent dye, in the cochlea, liver, and kidney of guinea pigs. Intravenous injection of rhodamine or rhodamine-encapsulated PLGA nanoparticles was used to target the fluorescent dye systemically to the liver, kidney, and cochlea, and these molecules were applied locally to the round window membrane (RWM) of the cochlea. The localization of rhodamine fluorescence in each region was quantitatively analyzed. After systemic application of rhodamine nanoparticles, fluorescence was identified in the liver, kidney, and cochlea. The systemic application of nanoparticles had a significant effect on targeted and sustained delivery of rhodamine to the liver but not the kidney or cochlea. Rhodamine nanoparticles placed on the RWM were identified in the scala tympani as nanoparticles, indicating that the PLGA nanoparticles can permeate through the RWM. Furthermore, the local application of rhodamine nanoparticles to the RWM was more effective in targeted delivery to the cochlea than systemic application. These findings indicate that PLGA nanoparticles can be an useful drug carrier to the cochlea via local application.