Nanoprecipitation Technique Research Articles

Controlled production of patchy particles from the combined effects of nanoprecipitation and vitrification.

Using molecular dynamics simulations, we study a simple and scalable method for fabricating patchy nanoparticles via the assembly of binary polymer blends under a rapid solvent exchange. Patchiness can be achieved by incorporating a glassy component, which kinetically traps the particle morphology along the path to the equilibrium configuration. Our simulations reveal that the number of surface patches increases for larger nanoparticles and for more asymmetric blend ratios, while the size distribution of the patches remains rather uniform. Other than multi-patch nanoparticles, Janus structures have been obtained for small nanoparticles. Further, ribbon structures with elongated surface domains have also been observed for more symmetric blend ratios. Our simulations demonstrate that the nanoprecipitation technique allows for independent control over nanoparticle size, patchiness and composition. This work gives microscopic insights on the static and dynamic properties of the self-assembled particles, and provides useful guidelines for fabricating tailored patchy nanoparticles for applications in various areas.

Stealth lipid polymer hybrid nanoparticles loaded with rutin for effective brain delivery – comparative study with the gold standard (Tween 80): optimization, characterization and biodistribution

The blood–brain barrier is considered the leading physiological obstacle hindering the transport of neurotherapeutics to brain cells. The application of nanotechnology coupled with surfactant coating is one of the efficacious tactics overcoming this barrier. The aim of this study was to develop lipid polymer hybrid nanoparticles (LPHNPs), composed of a polymeric core and a phospholipid shell entangled, for the first time, with PEG-based surfactants (SAA) viz. TPGS or Solutol HS 15 in comparison with the gold standard Tween 80, aiming to enhance brain delivery and escape opsonization. LPHNPs were successfully prepared using modified single-step nanoprecipitation technique, loaded with the flavonoid rutin (RU), extracted from the flowers of Calendula officinalis L., and recently proved as a promising anti-Alzheimer. The effect of the critical process parameters (CPP) viz. PLGA amount, Wlecithin/WPLGA ratio, and Tween 80 concentration on critical quality attributes (CQA); entrapment, size and size distribution, was statistically analyzed via design of experiments, and optimized using the desirability function. The optimized CPP were maintained while substituting Tween 80 with other PEG-SAA. All hybrid particles exhibited spherical shape with perceptible lipid shells. The biocompatibility of the prepared NPs was confirmed by hemolysis test. The pharmacokinetic assessments, post-intravenous administration to rats, revealed a significant higher RU bioavailability for NPs relative to drug solution. Biodistribution studies proved non-significant differences in RU accumulation within brain, but altered phagocytic uptake among various LPHNPs. The present study endorses the successful development of LPHNPs using PEG-SAA, and confirms the prospective applicability of TPGS and Solutol in enhancing brain delivery.

PLGA nanoparticles for intravitreal peptide delivery: statistical optimization, characterization and toxicity evaluation

Frequent intravitreal injections are currently used to overcome the ocular barriers and provide sufficient drug to the posterior eye segment. However, intravitreal injections have been associated with a number of complications and high treatment costs. To overcome these limitations, peptide-loaded poly(d,l-lactic-co-glycolic acid) nanoparticles (PLGA NPs) were developed using the nanoprecipitation technique and were optimized via Box–Behnken Design (BBD) and Response Surface Methodology (RSM). Developed NPs were evaluated for potential toxicity and cell apoptosis using the zebrafish embryo toxicity (ZET) model with titanium dioxide NPs and ethanol (1% v/v) serving as positive controls. Developed NPs had a size of 75.6–153.8 nm, a polydispersity index between 0.11 and 0.25 and a zeta potential of −9.4 to −46.0 mV. Loaded peptide was found to be stable under various experimental conditions tested. BBD and RSM were validated through the characterization of optimized formulations. Survival and hatching rates of NP-treated zebrafish 0–144 h post-fertilization were found to be normal with no significant malformations. Cellular apoptosis studies also endorsed the non-cytotoxic nature of the NPs. The overall results indicate that optimized PLGA nanoparticles could be a promising platform for efficient peptide delivery to the posterior segment of the eye.

PRAMIPEXOLE DIHYDROCHLORIDE LOADED MPEGPCL NANOSUSPENSION BY MODIFIED NANOPRECIPITATION: IN VITRO AND IN VIVO EVALUATION

AbstractAim and Objectives The present study was carried out to show the potential neuroprotective effects in both invitro and invivo pramipexole dihydrochloride nanosuspension for the treatment in Parkinson’s disease.Materials and Methods: Nanosuspension of pramipexole dihydrochloride was prepared with MPEG-PCL and Pluronic F68 by the process of modified nanoprecipitation technique with different concentrations of MPEG-PCL. The particle size, zeta potential, SEM, TEM and invitro dug release where performed. The cell viability study was performed by using SH-SY5Y cells. Further the formulation is evaluated for its antioxidant potential against rotenone induced neuronal damage in Wister rats such as enzymatic, non enzymatic antioxidants and histopathological evaluation.Result and Discussion: The nanoformulation shows least particle size of 143 nm and maximum zeta potential value 33.4 mv with 88.53% entrapment efficiency were observed with PMPNP 2 formulation. The SEM, TEM and invitro dug release of PMPNP 2 were shows spherical shape with controlled release when compared to other formulations. Further the MTT assay were performed by using SH-SY5Y cells which shows more than 50 % cell viability with 50 µl of PPMNP 2 nanoformulation. Further the antioxidant potential done in rotenone induced neuronal damage in Wister rats. The results showed elevation in the levels of enzymatic and non enzymatic antioxidants compared with neuronal toxic group. Further nanoformulation group showed decrease in levels of LPO which correlates with histopathological architecture.Conclusion: Our study concluded that nanoformulation showed better protective potential in both invitro and invivo compare to free drug for the treatment in Parkinson’s disease.Keywords: Pramipexoledihydrochloride; MPEG-PCL; SH-SY5Y cells; Nanoprecipitation; Parkinson’s disease.

Hydrophilic polymeric nanoparticles prepared from Delonix galactomannan with low cytotoxicity for ocular drug delivery

Delonix is a galactomannan polysaccharide extracted from the endosperm of Delonix regia plant. This study aims at the development of Delonix nanoparticle and assesses its potential for ocular delivery by evaluating its in-vitro stability, toxicity and cellular uptake. Fluorescent nanoparticles (BODIPY-loaded nanoparticles) were prepared by a Quality-by-Design modified nanoprecipitation technique. Optimized nanoparticles had mean sizes <240nm, PdI<0.2 and zeta potential of <−30mV. Mixture of surfactants with different hydrophilic-lipophilic balance controlled nanoparticle swelling. Nanoparticles, which were stable in the presence of simulated lachrymal fluid and lysozyme also sustained the release of BODIPY. In-vitro studies suggest no toxicity of the nanoparticles in concentration range of 100–1483.3μg/mL on retinal and corneal epithelial cells. Flow cytometry and confocal microscopy techniques showed that retinal cells but not corneal cells, uptake 18% of the nanoparticles. Therefore, Delonix nanoparticles could be a safe and promising tool for ocular drug delivery.

Preparation of Histone Deacetylase Inhibitor Vorinostat-Loaded Poly D, L-Lactide-co-Glycolide Polymeric Nanoparticles by Nanoprecipitation Method.

Nanotechnology is a comparatively new branch of science that includes harnessing the unique properties of particles that are nanometers in scale. Nanoparticles can be tailored in a precise fashion where their size, composition, and surface chemistry can be carefully controlled. The nanoprecipitation is a simple, powerful, and low-energy requiring technique, commonly used for the preparation of defined nanoparticles. Histone deacetylase inhibitor Vorinostat-loaded Poly D, L-lactide-co-glycolide (PLGA) polymeric nanoparticles were prepared by the nanoprecipitation technique. The technique commonly relies on the precipitation of a solvent-dissolved material as nanosize particles after the addition to a non-solvent-containing stabilizer. The particle size and size distribution of the Vorinostat polymeric nanoparticles are significantly influenced by the surfactants used in the fabrication process of the formulation. The surfactants prevent aggregate formation and improve the stability of the nanoparticles. The partitioning and evaporation of organic solvents allowed the formation of Vorinostat-loaded polymeric nanoparticles.

A novel nanoparticles impregnated ocular insert for enhanced bioavailability to posterior segment of eye: In vitro, in vivo and stability studies

The present investigation was carried out to demonstrate with the help of in vitro and in vivo studies that nanoparticles impregnated ocular inserts effectively delivers significant concentration of drug to the posterior segment of eye after topical administration for treatment of glaucoma. Drug loaded Nanoparticles and their ocular insert have been reported to reduce side effects of orally administered Acetazolamide. Eudragit NPs were prepared by the solvent diffusion nanoprecipitation technique. The prepared NPs were evaluated for various parameters such as particle size, zeta potential, % entrapment efficiency, % drug loading, DSC, FTIR, TEM and stability studies. Ocular inserts of NPs were prepared by solvent casting method. The prepared ocular inserts were evaluated for thickness, content uniformity, folding endurance, disintegration time, morphology and stability study. The NPs and ocular inserts were evaluated for in-vitro drug diffusion study, ex-vivo trans-corneal permeability study, in-vivo ocular tolerability and intra ocular pressure (IOP) reduction study. The optimized batch was stable for a period of 3months in lyophilized form. The optimized formulations had size range of 367nm±8nm, zeta potential around +7mV±1.3mV and 51.61%±3.84% entrapment efficiency with 19%±1.40% drug loading. The ex-vivo trans-corneal study showed higher cumulative corneal permeation, flux across corneal tissue (2.460±0.028μg/ml) and apparent corneal permeability (3.926×10−6cm2/s & 3.863×10−6cm2/s) from drug loaded Eudragit NPs and Ocular inserts as compared to drug solution (0.671±0.020μg/ml & 3.166×10−6cm2/s). In-vivo study showed the Eudragit NPs and ocular insert produced significant (P<0.001) lowering in intra ocular pressure compared with the solution of free drug after 3h of topical ocular administration. Plain Eudragit NPs caused no inflammation and/or discomfort in rabbit eyes and neither affected the intra ocular pressure establishing their safety and non irritancy.

Hyaluronic acid-coated, prodrug-based nanostructured lipid carriers for enhanced pancreatic cancer therapy

Context: Gemcitabine (GEM) and Baicalein (BCL) are reported to have anti-tumor effects including pancreatic cancer. Hyaluronic acid (HA) can bind to over-expressed receptors in various kinds of cancer cells.Objective: The aim of this study is to develop prodrugs containing HA, BCL and GEM, and construct nanomedicine incorporate GEM and BCL in the core and HA on the surface. This system could target the cancer cells and co-deliver the drugs.Methods: GEM-stearic acid lipid prodrug (GEM-SA) and hyaluronic acid-amino acid-baicalein prodrug (HA-AA-BCL) were synthesized. Then, GEM and BCL prodrug-based targeted nanostructured lipid carriers (HA-GEM-BCL NLCs) were prepared by the nanoprecipitation technique. The in vitro cytotoxicity studies of the NLCs were evaluated on AsPC1 pancreatic cancer cell line. In vivo anti-tumor effects were observed on the murine-bearing pancreatic cancer model.Results: HA-GEM-BCL NLCs were effective in entering pancreatic cancer cells over-expressing HA receptors, and showed cytotoxicity of tumor cells in vitro. In vivo study revealed significant tumor growth inhibition ability of HA-GEM-BCL NLCs in murine pancreatic cancer model.Conclusion: It could be concluded that HA-GEM-BCL NLCs could be featured as promising co-delivery, tumor-targeted nanomedicine for the treatment of cancers.

Synthesis and evaluation of alendronate-modified gelatin biopolymer as a novel osteotropic nanocarrier for gene therapy.

To synthesize an osteotropic alendronate functionalized gelatin (ALN-gelatin) biopolymer for nanoparticle preparation and targeted delivery of DNA to osteoblasts for gene therapy applications. Alendronate coupling to gelatin was confirmed using Fourier transform IR, (31)PNMR, x-ray diffraction (XRD) and differential scanning calorimetry. ALN-gelatin biopolymers prepared at various alendronate/gelatin ratios were utilized to prepare nanoparticles and were optimized in combination with DNA and gemini surfactant for transfecting both HEK-293 and MG-63 cell lines. Gelatin functionalization was confirmed using the above methods. Uniform nanoparticles were obtained from a nanoprecipitation technique. ALN-gelatin/gemini/DNA complexes exhibited higher transfection efficiency in MG-63 osteosarcoma cell line compared with the positive control. ALN-gelatin is a promising biopolymer for bone targeting of either small molecules or gene therapy applications.

SOLID LIPID NANOPARTICLE: FABRICATED THROUGH NANOPRECIPITATION AND THEIR PHYSICOCHEMICAL CHARACTERIZATION

&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;Aim of the present study was to formulate solid lipid nanoparticles (SLNs) and to determine their physicochemical parameters when stored at cold temperature in aqueous solution (D-SLNs) prior to biological application.&lt;strong&gt;&lt;/strong&gt;&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;SLNs were formulated though nanoprecipitation technique which comprised of stearic acid (lipid), poloxamer 188 and lecithin (surfactant). Physicochemical parameters were estimated though particle size analysis, polydispersity index, surface morphology analysis (Scanning electron microscopy and Transmission electron microscopy&lt;strong&gt;)&lt;/strong&gt; and cytotoxicity studies followed by live-dead staining through acridine orange and ethidium bromide.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;SLNs with spherical morphology were successfully fabricated as revealed though SEM and TEM investigations. Fabricated SLNs had the mean particle size ranging from 188 nm (SLNs) to 327 nm (D-SLNs). Zeta potential was found to be±14mV to±6mV and polydispersity index was 0.297±0.18 for SLNs without incubation and 0.538±0.07 for SLNs after incubation. No cytotoxicity was observed for SLNs.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;SEM and TEM investigations showed morphological variation in SLNs and D-SLNs. Dissimilarity in mean particle size, zeta potential and polydispersity index indicates the increase in size and aggregation of nanoparticles. No cytotoxic effects of SLNs were observed in normal cells, suggesting storage of nanoformulation in the aqueous state has no effect in context to cytotoxicity. Hence we conclude that prolonged storage of formulation at cold temperature causes the deterioration of polymeric formulation.&lt;/p&gt;

Design of smart GE11-PLGA/PEG-PLGA blend nanoparticulate platforms for parenteral administration of hydrophilic macromolecular drugs: synthesis, preparation and in vitro/ex vivo characterization

Active drug targeting and controlled release of hydrophilic macromolecular drugs represent crucial points in designing efficient polymeric drug delivery nanoplatforms. In the present work EGFR-targeted polylactide-co-glycolide (PLGA) nanoparticles were made by a blend of two different PLGA-based polymers. The first, GE11-PLGA, in which PLGA was functionalized with GE11, a small peptide and EGFR allosteric ligand, able to give nanoparticles selective targeting features. The second polymer was a PEGylated PLGA (PEG-PLGA) aimed at improving nanoparticles hydrophilicity and stealth features. GE11 and GE11-PLGA were custom synthetized through a simple and inexpensive method. The nanoprecipitation technique was exploited for the preparation of polymeric nanoparticles composed by a 1:1weight ratio between GE11-PLGA and PEG-PLGA, obtaining smart nanoplatforms with proper size for parenteral administration (143.9±5.0nm). In vitro cellular uptake in EGFR-overexpressing cell line (A549) demonstrated an active internalization of GE11-functionalized nanoparticles. GE11-PLGA/PEG-PLGA blend nanoparticles were loaded with Myoglobin, a model hydrophilic macromolecule, reaching a good loading (2.42% respect to the theoretical 4.00% w/w) and a prolonged release over 60days. GE11-PLGA/PEG-PLGA blend nanoparticles showed good in vitro stability for 30days in physiological saline solution at 4°C and for 24h in pH 7.4 or pH 5.0 buffer at 37°C respectively, giving indications about potential storage and administration conditions. Furthermore ex vivo stability study in human plasma using fluorescence Single Particle Tracking (fSPT) assessed good GE11-PLGA/PEG-PLGA nanoparticles dimensional stability after 1 and 4h. Thanks to the versatility in polymeric composition and relative tunable nanoparticles features in terms of drug incorporation and release, GE11-PLGA/PEG-PLGA blend NPs can be considered highly promising as smart nanoparticulate platforms for the treatment of diseases characterized by EGFR overexpression by parenteral administration .

Nanoparticles responsive to the inflammatory microenvironment for targeted treatment of arterial restenosis

Coronary arterial disease (CAD) remains the leading cause of death globally. Percutaneous coronary interventions are frequently used nonsurgical techniques for treating CAD, which may unfortunately lead to arterial restenosis. Currently, there are no effective drugs that can thoroughly prevent restenosis. We hypothesize inflammation-triggerable nanomedicines may function as effective therapeutics for targeted therapy of restenosis, by preferentially releasing their payload at the diseased site. To demonstrate our hypothesis and develop targeted nanotherapies for restenosis, this study was designed to examine effectiveness of nanomedicines responsive to the inflammatory microenvironment with mild acidity and high reactive oxygen species (ROS). To this end, an acetalated β-cyclodextrin (β-CD) material (Ac-bCD) was synthesized as a pH-responsive carrier material, while a ROS-responsive material (Ox-bCD) was produced by hydrophobic functionalization of β-CD with an oxidation-labile group. Based on these two responsive materials, either pH- or ROS-responsive nanoparticles (NPs) were produced by a nanoprecipitation technique and fully characterized. Using rapamycin (RAP) as a candidate drug, responsive nanotherapies were fabricated. Invitro hydrolysis and release studies confirmed these nanovehicles and nanotherapies exhibited desirable responsive behaviors. Both invitro cell culture and invivo evaluations revealed their good safety profile. These responsive NPs could be effectively internalized by rat vascular smooth muscle cells, which in turn notably potentiated anti-proliferation and anti-migration activities of RAP. After intravenous (i.v.) injection, NPs may be accumulated at the injured site in the carotid artery of rats subjected to balloon angioplasty injury. Compared with a non-responsive nanotherapy based on poly(lactide-co-glycolide), treatment with either pH- or ROS-responsive nanotherapy by i.v. injection more effectively attenuated neointimal hyperplasia in a rat model of arterial restenosis. Accordingly, nanotherapeutics responsive to the inflammatory microenvironment hold great potential for the management of vascular restenosis by selectively releasing drug molecules at the inflamed sites.

PVP- coated naringenin nanoparticles for biomedical applications – In vivo toxicological evaluations

Naringenin (NAR) is one of the naturally occurring flavonoids found in citrus fruits and exerts a wide variety of pharmacological activities. The clinical relevance of naringenin is limited by its low solubility and minimal bioavailability, owing to its largely hydrophobic ring structure. The aim of the present study is to develop a novel naringenin nanoparticle system (NAR NP) using simple nanoprecipitation technique with polyvinylpyrrolidone (PVP) as the hydrophilic carrier. The synthesized nanoparticles were characterized using XRD, FTIR, SEM and EDX. The characterization study revealed the nanoscale properties and the interactions between NAR and PVP. In vivo toxicological evaluations were carried out at various doses (1, 5, 10 & 50 mg/kg body wt) in male Sprague-Dawley rats in comparison with silver nanoparticle (AgNP) at toxic concentration (50 mg/kg body wt). The altered hepatotoxicity markers, hematology parameters and antioxidant defense system were observed in AgNP- treated rats. But NAR NP – treated rats did not show any biochemical alterations and improved the antioxidant defense indices when compared to control group, by virtue of the pharmacological properties exerted by NAR. The modulatory effect of NAR NP over inflammatory and stress signaling cascades were confirmed by the normalized mRNA expressions of NF-κB, TNF-α and IL-6. The histopathological analysis of liver, kidney and heart reinforce our findings. These studies provide preliminary answers to some of the key biological issues raised over the use and safety of nanoparticles for diagnostic and therapeutic applications. Consequently, we suggest that the safe NAR NP can be used to reduce the dosage of NAR, improve its bioavailability and merits further investigation for therapeutic applications.

Prolonged exposure of colon cancer cells to 5-fluorouracil nanoparticles improves its anticancer activity

In this study, we aimed to improve the anticancer effect of 5-FU on human colon cancer cell lines by incorporating in poly(d,l lactic-co-glycolic acid) (PLGA) nanoparticles (NPs). The 5-FU-PLGA NPs were prepared by nanoprecipitation technique. Prepared NPs were moderately dispersed with an average diameter of 133±25.19nm. Scanning Electron Microscope (SEM) images revealed spherical structures with subtle surface irregularity. Free 5-FU dose–response curves were constructed (12.5–2000μM) using MTT assay on HCT 116 and HT-29 cell lines for 1, 3, and 5days. The calculated IC50 on HCT 116 were 185μM after 1day, 11.3μM after 3days, and 1.48μM after 5days. On HT-29, IC50 was only reached after 5days of 5-FU treatment (11.25μM). The HCT 116 viability following treatment with 100μM 5-FU in free or NPs forms for 3days was 38.8% and 18.6%, respectively. Similarly, when 250μM was applied, HCT 116 viability was 17.03% and 14.6% after treatment with free and NPs forms of 5-FU, respectively. Moreover, HT-29 cell viability after 250μM 5-FU treatment in free or NPs forms was 55.45% and 34.01%, respectively. We also noticed that HCT 116 cells were more sensitive to 5-FU-PLGA NPs as compared to HT-29 cells. Overall, our data indicate that 5-FU activity is time dependent and the prolonged effects created by PLGA NPs may contribute, at least in part, to the noticed enhancement of the anticancer activity of 5-FU drug.

Biopharmaceutical Evaluation of Novel Cyclosporine A Nano-matrix Particles for Inhalation.

This study was undertaken to evaluate the biopharmaceutical properties of cyclosporine A (CsA)-loaded nano-matrix particles for inhalation. Nano-matrix particles of CsA with mannitol (nCsAm) were prepared by a flash nano-precipitation technique employing a multi-inlet vortex mixer and evaluated in terms of physicochemical properties, anti-inflammatory effect in the rat model of airway inflammation, pharmacokinetic behavior, and distributions of CsA to side-effect-related organs after intratracheal administration. In nCsAm, spherical nano-particles of CsA were covered with mannitol and the mean particle size was 1.3μm. The in vitro Next Generation Impactor analysis demonstrated fine inhalation performance with a fine particle fraction value of 65.8%. Intratracheal nCsAm (100μg-CsA/rat) significantly attenuated the recruitment of inflammatory cells into the airway in the rat model of airway inflammation, followed by suppression of the inflammatory biomarkers. After intratracheal nCsAm at a pharmacologically effective dose (100μg-CsA/rat), there was a 42-47-fold decrease in the distribution of CsA to side-effect-related organs such as the kidney and liver compared with oral CsA at a toxic dose (10mg-CsA/kg), potentially leading to avoidance of systemic side-effects of CsA. Upon these findings, nCsAm prepared with the flash nano-precipitation technique could be a novel dosage form of CsA for inhalation therapy of airway inflammation with a better safety margin.

Thyrotropin-Releasing Hormone Loaded and Chitosan Engineered Polymeric Nanoparticles: Towards Effective Delivery of Neuropeptides.

Thyrotropin-Releasing Hormone (TRH), a tripeptide amide with molecular formula L-pGlu-L-His-L- Pro-NH2, is used in the treatment of brain/spinal injury and certain central nervous system (CNS) disorders, including schizophrenia, Alzheimer's disease, epilepsy, depression, shock and ischemia due to its profound effects on the CNS. However, TRH's therapeutic activity is severely hampered because of instability and hydrophilicity owing to its peptidic nature which results into ineffective penetration into the blood brain barrier. In the present study, we report the synthesis and stability studies of novel chitosan engineered TRH encapsulated poly(lactide-co-glycolide) (PLGA) based nanoformulation. The aim of such an encapsulation is to allow effective delivery of TRH in biological systems as the peptidase degrade naked TRH. The synthesis of TRH was carried out manually in solution phase followed by its encapsulation using PLGA to form polymeric nanoparticles (NPs) via nanoprecipitation technique. Different parameters such as type of organic phase, concentration of stabilizer, ratio of organic phase and aqueous phase, rate of addition of organic phase were optimized, tested and evaluated for particle size, encapsulation efficiency, and stability of NPs. The TRH-PLGA NPs were then surface modified with chitosan to achieve positive surface charge rendering them potential membrane penetrating agents. PLGA, PLGA-TRH, Chitosan-PLGA and Chitosan-PLGA-TRH NPs were characterized and analyzed using Dynamic Light Scattering (DLS), Transmissiom Electron Microscopy (TEM) and Infra-red spectroscopic techniques.

Polylactic acid and poly(3-hydroxybutyrate-co-3-hydroxyvalerate) nano and microparticles for packaging bioplastic composites

Two methods, nanoprecipitation and emulsification/solvent evaporation with different solvents, to prepare nano and microparticles of polylactic acid (PLA) and PHBV are investigated. The obtained particles are characterized in terms of morphology by SEM and thermal properties by DSC and TGA. The objective is the preparation of PLA and PHBV nano and microparticles, with controlled shape and size distribution, for their further inclusion into biopolymer matrices such as PLA, PHBV or thermoplastic starch matrices. The purpose is the use of these biocomposites in the sector of wrapping and packaging. Good thermal properties of the nano and microparticles are important to the posterior processing as extrusion film technique. Although the smallest particles are obtained for PLA using nanoprecipitation technique with THF as solvent, these nanoparticles show a low thermal stability. The emulsification technique using dichloromethane as solvent shows to be a good option to obtain, for PLA and PHBV, spherical particles with controlled size and adequate thermal stability. The reproducibility of the selected method is studied for up-scaling nano and microparticle production to pre-industrial level. This study of reproducibility using statistical analysis shows the robustness of the methodology.

Controlled release of drug and better bioavailability using poly(lactic acid-co-glycolic acid) nanoparticles

Tamoxifen (Tmx) embedded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (PLGA-Tmx) is prepared to evaluate its better DNA cleavage potential, cytotoxicity using Dalton’s lymphoma ascite (DLA) cells and MDA-MB231 breast cancer cells. PLGA-Tmx nanoparticles are prepared through emulsified nanoprecipitation technique with varying dimension of 17–30nm by changing the concentrations of polymer, emulsifier and drug. Nanoparticles dimension are measured through electron and atomic force microscopy. Interactions between tamoxifen and PLGA are verified through spectroscopic and calorimetric methods. PLGA-Tmx shows excellent DNA cleavage potential as compared to pure Tmx raising better bioavailability. In vitro cytotoxicity studies indicate that PLGA-Tmx reduces DLA cells viability up to ∼38% against ∼15% in pure Tmx. Hoechst stain is used to detect apoptotic DLA cells through fluorescence imaging of nuclear fragmentation and condensation exhibiting significant increase of apoptosis (70%) in PLGA-Tmx vis-à-vis pure drug (58%). Enhanced DNA cleavage potential, nuclear fragmentation and condensation in apoptotic cells confirm greater bioavailability of PLGA-Tmx as compared to pure Tmx in terms of receptor mediated endocytosis. Hence, the sustained release kinetics of PLGA-Tmx nanoparticles shows much better anticancer efficacy through enhanced DNA cleavage potential and nuclear fragmentation and, thereby, reveal a novel vehicle for the treatment of cancer.

Development of biodegradable polymeric nanoparticles for encapsulation, delivery, and improved antifungal performance of natamycin

ABSTRACTThe aim of this study was to evaluate biodegradable poly(lactide‐co‐glycolide) nanoparticles as potential nano‐delivery systems for the food antifungal compound natamycin. Natamycin‐loaded nanoparticles were prepared at various ratios polymer/antifungal by the nanoprecipitation technique, resulting in nano‐size particles (80–120 nm) with a narrow distribution and a spherical morphology. Complexation of natamycin with PLGA and active participation to the nanoparticle formation were evidenced by a mean diameter reduction of 10–30 nm, although encapsulation levels remained low due to the zwitterionic and partially hydrophilic nature of natamycin. Physical state analyses highlighted the presence of natamycin in an amorphous or molecularly dispersed state within the polymeric matrix. This translates into high availability of free antifungal molecules reflected in burst release and fast in vitro release kinetics rates as well as enhanced antifungal performance against the model food yeast Saccharomyces cerevisiae, offering a potential benefit for antifungal protection compared with the commercially available natamycin products. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 43736.

Development and evaluation of olmesartan medoxomil loaded PLGA nanoparticles

The purpose of the present study was to develop olmesartan medoxomil (OLM) loaded poly (d,l-lactide-co-glycolide) (PLGA) nanoparticles by nanoprecipitation technique. Olmesartan medoxomil nanoparticles (F1–F3) were prepared using PLGA as polymer and Pluronic acid 127 as a surfactant. Developed PLGA nanoparticles were evaluated for particle size, polydispersity index (PI), differential scanning calorimetry (DSC), Fourier transforms infrared (FTIR) spectroscopy, powder X-ray diffraction (XRD), scanning electron microscopy (SEM), drug entrapment efficiency (EE%) and in vitro drug release. Optimised PLGA nanoparticle (F3) had particle size of 97.8 ± 6.3 nm, EE of 58.33% and drug release of 37.1% after 24 h of study. SEM images confirmed that developed nanoparticles were spherical in shape with a smooth surface. DSC, FTIR, and XRD spectra indicated formation of PLGA nanoparticles. The results suggest that PLGA polymer-based nanoparticle could be a potential option for sustained drug delivery of OLM.