Poly(d,l-lactic-co-glycolic) Acid Nanoparticles Research Articles

DEVELOPMENT AND OPTIMIZATION OF POLYMERIC NANOPARTICLES OF GLYCYRRHIZIN: PHYSICOCHEMICAL CHARACTERIZATION AND ANTIOXIDANT ACTIVITY

Objective: The aim of the present study to develop, optimize and characterize Poly (D, L-lactic-co-glycolic) acid (PLGA) nanoparticles (NPs) loaded with isolated Glycyrrhizin (Glyc) and investigate for antioxidant activity. Methods: PLGA nanoparticles loaded with Glycyrrhizin were synthesized by an adapted emulsion-evaporation method. Nanoparticles were evaluated for particle size, entrapment efficiency and Polydispersiblity index (PDI). Further, Box Benkhen design was applied for optimization of the formulation parameters and the effect of three independent variables such as PLGA concentration, amount of glycyrrhizin, polyvinyl alcohol (PVA) concentration on particle size, polydispersiblity index and the entrapment efficiency (response variables) were investigated. The antioxidant capacity of optimized nanoparticle formulation loaded with glycyrrhizin was compared with free glycyrrhizin by DPPH assay. Results: The particle size, entrapment efficiency and PDI of optimized Glyc-NPs was found to be 144.20 nm, 68.0% and 0.315 respectively. Optimized Glyc-NPs showed sustained release of drug 79.06% in 48 hours with improved free radical scavenging activity than isolated Glycyrrhizin. Conclusion: PLGA nanoparticles were found to be suitable carrier for Glycyrrhizin at lower levels than originally required for enhanced functional properties.

Alpha Tocopherol Loaded Polymeric Nanoparticles: Preparation, Characterizations, and In Vitro Assessments Against Oxidative Stress in Spinal Cord Injury Treatment.

Spinal cord injury (SCI) is characterized by mechanical injury or trauma to the spinal cord. Currently, SCI treatment requires extremely high doses of neuroprotective agents, which in turn, causes several adverse effects. To overcome these limitations, the present study focuses on delivery of a low but effective dose of a naturally occurring antioxidant, α-tocopherol (α-TP). Calcium alginate nanoparticles (CA-NP) and poly D,L-lactic-co-glycolic acid nanoparticles (PLGA-NP) prepared by ionotropic gelation and solvent evaporation technique had particle size of 21.9 ± 11.19 and 152.4 ± 10.6nm, respectively. Surface morphology, surface charge, as well as particle size distribution of both nanoparticles were evaluated. Entrapment of α-TP into CA-NP and PLGA-NP quantified by UPLC showed entrapment efficiency of 4.00 ± 1.63% and 76.6 ± 11.4%, respectively. In vitro cytotoxicity profiles on human astrocyte-spinal cord (HA-sp) showed that blank CA-NP at high concentrations reduced the cell viability whereas blank PLGA-NP showed relatively safer cytotoxic profiles. In addition, PLGA nanoparticles encapsulated with α-TP (α-TP-PLGA-NP) in comparison to α-TP alone at high concentrations were less toxic. Pretreatment of HA-sp cells with α-TP-PLGA-NP showed two-fold higher anti-oxidative protection as compared to α-TP alone, when oxidative stress was induced by H2O2. In conclusion, CA-NP were found to be unsuitable for treatment of SCI due to their cytotoxicity. Comparatively, α-TP-PLGA-NP were safer and showed high degree of protection against oxidative stress than α-TP alone.

Duodenal Histomorphological Changes in Broilers Administered poly d, l-lactic-coglycolic acid (PLGA ) Nanoparticles Encapsulated with Peptide

This research was carried out to evaluate the effect of poly d, l-lactic-coglycolic acid(PLGA) nanoparticles loaded with peptide (as vaccine) on histomorphological in duodenum of broiler chick. A total of ninety eight, one day old ,unsexed broiler( Rose) chicks were divided randomly into seven groups( 2 replicate in each group) as follows:G1-control,G2 - chicks received traditional vaccine of infectious bursal disease(Volvac@ IBD MLV) ,G3 – Chicks Received PLGA nanoparticles only, G4,G5,G6 and G7 – chicks were received prepared vaccine at 160, 80, 40,and 20 μg of peptide loaded PLGA respectively. At the end of the experiment histopathological examination of duodenum section and histomorphological changes were examined. The histopathological examination of duodenal sections shows an elongation and infiltration of lamina propria (LP) with increase villi height and crypt depth in groups that received PLGA alone and those received peptide loaded PLGA. At the same time these groups reveal an increase in mucosal thickness and in length and width of villi. The histomorphological examination in this study show thicker mucosal layer with deeper crypt in duodenum of broilers that subjected to PLGA administration alone or to different concentration of peptide loaded PLGA compared to G1 and G2. These findings are accompanied by a high density of goblet cells and lower villus hight/crypt depth (V/CD) ratio. All groups show mononuclear cells (MNCs) infiltration in submucosa ofduodenum. In-conclusion, the administration of PLGA nanoparticles is strongly linked to the improvement of the physiological and immunological features of the birds.

Lipid Vesicles Loaded with an HIV-1 Fusion Inhibitor Peptide as a Potential Microbicide.

The effective use of fusion inhibitor peptides against cervical and colorectal infections requires the development of sustained release formulations. In this work we comparatively study two different formulations based on polymeric nanoparticles and lipid vesicles to propose a suitable delivery nanosystem for releasing an HIV-1 fusion inhibitor peptide in vaginal mucosa. Polymeric nanoparticles of poly-d,l-lactic-co-glycolic acid (PLGA) and lipid large unilamellar vesicles loaded with the inhibitor peptide were prepared. Both formulations showed average sizes and polydispersity index values corresponding to monodisperse systems appropriate for vaginal permeation. High entrapment efficiency of the inhibitor peptide was achieved in lipid vesicles, which was probably due to the peptide’s hydrophobic nature. In addition, both nanocarriers remained stable after two weeks stored at 4 °C. While PLGA nanoparticles (NPs) did not show any delay in peptide release, lipid vesicles demonstrated favorably prolonged release of the peptide. Lipid vesicles were shown to improve the retention of the peptide on ex vivo vaginal tissue in a concentration sufficient to exert its pharmacological effect. Thus, the small size of lipid vesicles, their lipid-based composition as well as their ability to enhance peptide penetration on vaginal tissue led us to consider this formulation as a better nanosystem than polymeric nanoparticles for the sustained delivery of the HIV-1 fusion inhibitor peptide in vaginal tissues.

Effect of nanoencapsulation using PLGA on antioxidant and antimicrobial activities of guabiroba fruit phenolic extract

Guabiroba fruit has been highlighted for its high phytochemical content, particularly of phenolic compounds. The stability, bioavailability, and bioactivity of these compounds can be enhanced by nanoencapsulation, to improve functionality. Poly(d,l-lactic-co-glycolic) acid (PLGA) nanoparticles containing phenolic extract of guabiroba (GPE) were synthesized by an adapted emulsion-evaporation method and their physico-chemical and functional properties were studied at two lactic to glycolic acid ratios (50:50 and 65:35). Higher (P<0.05) or equivalent antioxidant capacity compared to free GPE were observed for GPE-loaded nanoparticles. Free extract and PLGA nanoparticles were effective inhibitors of Listeria innocua, with lower (P<0.05) GPE concentrations required for inhibition when nanoencapsulated. Also, reduction of ROS generation in non-cancer cells was achieved with lower GPE concentrations (P<0.05) after encapsulation. These results suggest that PLGA nanoparticles can be used as a delivery system for phenolic compounds at lower levels than originally required for enhanced functional properties.

Biodegradable nanoparticles loaded with tetrameric melittin: preparation and membrane disruption evaluation.

Melittin is the main component of bee venom consisting of 26 amino acids that has multiple effects, including antibacterial, antiviral and anti-inflammatory in various cell types. This peptide forms pores in biological membranes and triggers cell death. Therefore it has potential as an anti-cancer therapy. However, the therapeutic application of melittin is limited due to its main side effect, hemolysis, which is especially pronounced following intravenous administration. In the present study, we formulated tetrameric melittin-carrying poly-D,L-lactic-co-glycolic acid nanoparticles (PLGA-NPs) and analyzed the lytic activity of this system on liposomes that resembles breast cancer cells. Tetrameric melittin binds avidly to PLGA-NPs with an encapsulation efficiency of 97% and retains its lytic activity demonstrating the effectiveness of PLGA-NPs as nanocarriers for this cytolytic peptide.

Enhancing the in vitro anticancer activity of albendazole incorporated into chitosan-coated PLGA nanoparticles

To improve the solubility and anticancer activity of albendazole (ABZ), chitosan (CS)-coated poly-dl-lactic-co-glycolic acid (PLGA) nanoparticles were developed. CS was used to coat ABZ-loaded PLGA nanoparticles to enhance both mucoadhesiveness and colloidal stability. CS-coated PLGA nanoparticles were prepared by suspending the nanoparticles in CS solution after solvent diffusion. The CS-coated PLGA nanoparticles were characterized, and ABZ release was studied in vitro from various formulations. The mucoadhesive properties and in vitro anticancer activities of CS-coated PLGA nanoparticles were investigated by measurement of zeta potentials and the MTT assay, respectively. Spherical nanoparticles below 500nm in diameter were successfully prepared; the particle size distribution was narrow. Complete encapsulation of ABZ in CS-coated PLGA nanoparticles was confirmed by SEM, FTIR, DSC, and XRD. The particle sizes of CS-coated PLGA nanoparticles were in the range of 260–480nm; the encapsulation efficiency was 43.4–54.6%; and the yield 58.5–67.8%. The zeta potential of CS-coated nanoparticles was above +27mV and stability was maintained for 4 weeks. At pH 7.4, the in vitro release of ABZ from nanoparticles (P188-5) was 200-fold higher than that from untreated ABZ; this persisted for 12h. Moreover, ABZ release from CS-coated PLGA nanoparticles (P188-CS0.5) was 1.5-fold higher than that from untreated ABZ at pH 1.2. Additionally, the ABZ-loaded CS-coated nanoparticles exhibited superior mucoadhesion and improved cytotoxicity. The results show that CS coating of PLGA nanoparticles may improve the anticancer effect and the mucoadhesive properties of ABZ-loaded nanoparticles.

Novel functionalization strategies of polymeric nanoparticles as carriers for brain medications.

For targeted brain delivery, nanoparticles (NPs) should bypass the blood-brain barrier (BBB). Novel functionalization strategies, based on low-density lipoprotein receptor (LDLR) binding domain, have been here tested to increase the brain targeting efficacy of poly d,l-lactic-co-glycolic acid (PLGA) NPs, biodegradable and suited for biomedical applications. Custom-made PLGA NPs were functionalized with an apolipoprotein E modified peptide (pep-apoE) responsible for LDLR binding, or with lipocalin-type prostaglandin-d-synthase (L-PGDS), highly expressed in the brain. At the comparison of pep-apoE and L-PGDS sequences, a highly homologs region was here identified, indicating that also L-PGDS could bind LDLR. Non-functionalized and functionalized NPs did not affect the viability of cultured human dendritic cells, protagonists of the immune response, and did not activate them to a proinflammatory profile. At 2 h after intravenous injection in mice, functionalized, but not the non-functionalized ones, fluorescent-tagged NPs were observed in the cerebral cortex parenchyma. The NPs were mostly internalized by neurons and microglia; glial cells showed a weak activation. The findings indicate that the tested functionalization strategies do not elicit adverse immune responses and that the peptidic moieties enable BBB traversal of the NPs, thus providing potential brain drug carriers. These could be especially effective for brain diseases in which LDLR is involved. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 847-858, 2017.

The fabrication and characterization of a PLGA nanoparticle–Pheroid® combined drug delivery system

The combination of polymeric nanoparticles (NPs) as a core and lipid vesicles as a shell has emerged to be a robust and promising drug delivery strategy. This study explores the development of a novel combined delivery system where poly d,l, lactic-co-glycolic acid (PLGA) NPs are entrapped within Pheroid® drug delivery system. The solid NPs were combined with the Pheroid® vesicles using two different methods: pre-mix and post-mix. The surface properties of the PLGA NPs were altered through the inclusion (pos-NPs) and exclusion (neg-NPs) of chitosan (CT) and polyethylene glycol (PEG), to evaluate their interaction with the Pheroid® Vesicles. The average particle size of the novel NP–Pheroid® combined system ranged from approximately 1990–2450 nm while the zeta potential (ZP) ranged from −18 to −30 mV, measured using dynamic light scattering (DLS) and electrophoretic velocity techniques, respectively. The NP/Pheroid® mixing ratio experiment indicated that a maximum of 2.5% (w/v) NPs can be optimally added to the Pheroid® vesicles without compromising the structure and the stability of the NP–Pheroid® combined system. Visual analysis of this system was done through transmission electron microscopy (TEM), cryogenic (cryo) TEM and confocal laser scanning microscopy (CLSM) techniques to obtain adequate information of this novel combined drug delivery system which includes the localization of the PLGA NPs with the Pheroid ® vesicles.

Transient aggregation of chitosan-modified poly(d,l-lactic-co-glycolic) acid nanoparticles in the blood stream and improved lung targeting efficiency

Chitosan (CS)-modified poly(d,l-lactic-co-glycolic) acid (PLGA) nanoparticles (NPs) were prepared and their lung targetability after intravenous administration was elucidated. PLGA NPs (mean diameter: 225nm; polydispersity index: 0.11; zeta potential: −15mV), 0.2% (w/v) CS-coated PLGA NPs (CS02-PLGA NPs, mean diameter: 264nm; polydispersity index: 0.17; zeta potential: −7mV), and 0.5% (w/v) CS-coated PLGA NPs (CS05-PLGA NPs, mean diameter: 338nm; polydispersity index: 0.23; zeta potential: 12mV) were fabricated by a modified solvent evaporation method. PLGA NPs maintained their initial particle size in different media, such as human serum albumin (HSA) solution, rat plasma, and distilled water (DW), while CS05-PLGA NPs exhibited the formation of aggregates in early incubation time and disassembly of those into the NPs in late incubation time (at 24h). According to the sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis, the binding affinity of CS05-PLGA NPs with HSA and rat plasma was higher than that of PLGA NPs. By a near-infrared fluorescence (NIRF) imaging test in the mouse, the selective accumulation of CS05-PLGA NPs, rather than PLGA NPs, in lung tissue was demonstrated. These findings suggest that CS05-PLGA NPs can form transient aggregates in the blood stream after intravenous administration and markedly improve lung targeting efficiency, compared with PLGA NPs.

Tailoring PLGA nanoparticle release profiles via centrifugal fractioning

Event Abstract Back to Event Tailoring PLGA nanoparticle release profiles via centrifugal fractioning Dipankar Dutta1*, Mariama Salifu1*, Rachael W. Sirianni1, 2* and Sarah E. Stabenfeldt1* 1 Arizona State University, School of Biological and Health Systems Engineering, United States 2 Barrow Neurological Institute, Barrow Brain Tumor Research Center, United States Introduction: Poly(D,L-lactic-co­-glycolic) acid (PLGA)-based nanoparticles (NP) are uniquely posed to overcome limitations of conventional drug delivery systems. However, tailoring cargo/payload release profiles from PLGA NPs typically requires the optimization of the multi-parameter NP formulation, where small changes may cause drastic shifts in the resulting release profiles[1],[2]. In this study, we aimed to establish whether refining the average diameter of NP populations through centrifugal fractioning after particle formulation represents a feasible tool to tailor PLGA NP release characteristics. We hypothesized that the average NP size would directly affect protein loading and subsequent release characteristics. Materials and Methods: PLGA NPs were produced via double-emulsion followed by solvent evaporation to encapsulate the model protein, bovine serum albumin (BSA). NPs were then subjected to centrifugal fractioning protocols varying in both spin time and force. After separation of supernatant and pellet, NP size distributions of initial and fractioned groups were determined using scanning electron microscopy. Release profiles were quantified by determining protein encapsulation efficiencies and in vitro release assays. Statistical analyses were performed using analysis of variance with Tukey’s post-hoc test. Results and Discussion: Centrifugal fractioning significantly modulated NP size distribution as a function of spin time and force without negatively affecting yield and NP morphology. Average diameters for all groups in the study ranged between 211.2–707.5nm relative to 340.9nm for the initial batch of NPs. Additionally, we found the average NP diameter was related to marked alterations in encapsulation efficiencies (range: 36.4-49.4%; Fig 1A), burst release (range: 15.8-49.1%; Fig 1B), protein release rate (Fig 1C), and time for total cargo release (range: 38-78 days; Fig 1D). Our data corroborated previous reports relating NP size with such release characteristics[3],[4]. However, this is the first study, to our knowledge, to directly compare NP population size and protein release profile while holding all formulation parameters constant. Conclusion: Previous studies have evaluated the influence of the fabrication parameters on the cargo loading and release from PLGA particles to provide general formulation trends on obtaining broad release profile characteristics. However, seemingly simple changes in the NP formulation may ultimately lead to a loss of desirable attribute(s). We report that protein encapsulation efficiency and several parameters of the release curve are correlated to t. Thus centrifugal fractioning represents a potential tool for tuning NP properties without modifying formulation parameters. Figure 1: Encapsulation efficiency and duration of release was directly proportional to the average particle diameter (A and D). Conversely, the magnitude of the burst release and the rate of protein release were inversely proportional to average particle diameter (B and C). Linear regression was used to empirically model trends (solid line) with 95% confidence interval (dotted lines). NIH (1DP2HD084067; SES); NSF (1454282; SES); ASU Start-up Funds (SES); Ben and Catherine Ivy Foundation (RWS); DoD (W81XWH-14-1-0311; RWS)

Enhanced anti-tumor immune responses and delay of tumor development in human epidermal growth factor receptor 2 mice immunized with an immunostimulatory peptide in poly(D,L-lactic-co-glycolic) acid nanoparticles.

IntroductionCancer vaccines have the potential to induce curative anti-tumor immune responses and better adjuvants may improve vaccine efficacy. We have previously shown that Hp91, a peptide derived from the B box domain in high-mobility group box protein 1 (HMGB1), acts as a potent immune adjuvant.MethodIn this study, Hp91 was tested as part of a therapeutic vaccine against human epidermal growth factor receptor 2 (HER2)-positive breast cancer.ResultsFree peptide did not significantly augment immune responses but, when delivered in poly(D,L-lactic-co-glycolic) acid nanoparticles (PLGA-NPs), robust activation of dendritic cells (DCs) and increased activation of HER2-specific T cells was observed in vitro. Vaccination of HER2/neu transgenic mice, a mouse breast cancer model that closely mimics the immune modulation and tolerance in some breast cancer patients, with Hp91-loaded PLGA-NPs enhanced the activation of HER2-specific cytotoxic T lymphocyte (CTL) responses, delayed tumor development, and prolonged survival.ConclusionsTaken together these findings demonstrate that the delivery of the immunostimulatory peptide Hp91 inside PLGA-NPs enhances the potency of the peptide and efficacy of a breast cancer vaccine.Electronic supplementary materialThe online version of this article (doi:10.1186/s13058-015-0552-9) contains supplementary material, which is available to authorized users.

Development and optimization of quercetin-loaded PLGA nanoparticles by experimental design.

Background and aimsQuercetin is a flavonoid with good antioxidant activity, and exhibits various important pharmacological effects. The aim of the present work was to study the influence of formulation factors on the physicochemical properties of quercetin-loaded polymeric nanoparticles in order to optimize the formulation.Materials and methodsThe nanoparticles were prepared by the nanoprecipitation method. A 3-factor, 3-level Box-Behnken design was employed in this study considering poly(D,L-lactic-co-glycolic) acid (PLGA) concentration, polyvinyl alcohol (PVA) concentration and the stirring speed as independent variables. The responses were particle size, polydispersity index, zeta potential and encapsulation efficiency.Results The PLGA concentration seemed to be the most important factor influencing quercetin-nanoparticle characteristics. Increasing PLGA concentration led to an increase in particle size, as well as encapsulation efficiency. On the other hand, it exhibited a negative influence on the polydispersity index and zeta potential. The PVA concentration and the stirring speed had only a slight influence on particle size and polydispersity index. However, PVA concentration had an important negative effect on the encapsulation efficiency. Based on the results obtained, an optimized formulation was prepared, and the experimental values were comparable to the predicted ones.Conclusions The overall results indicated that PLGA concentration was the main factor influencing particle size, while entrapment efficiency was predominantly affected by the PVA concentration.

Transferrin-conjugated doxorubicin-loaded lipid-coated nanoparticles for the targeting and therapy of lung cancer.

In the present study, a targetable vector was developed for the targeted delivery of anticancer agents, consisting of lipid-coated poly D,L-lactic-co-glycolic acid nanoparticles (PLGA-NP) that were modified with transferrin (TF). Doxorubicin (DOX) was used as a model drug for lung cancer therapy. The use of these NPs combined the advantages and avoided the disadvantages exhibited individually by liposomes and polymeric NPs during drug delivery. The lipid coating of the polymeric core was confirmed by transmission electron microscopy. The physicochemical characteristics of transferrin-conjugated lipid-coated NPs (TF-LP), including the particle size, zeta potential, morphology, encapsulation efficiency and in vitro DOX release, were also evaluated. The cellular uptake investigation in the present study found that TF-LP was more efficiently endocytosed by the A549 cells, than LP and PLGA-NPs. Furthermore, the anti-proliferative effect exhibited by DOX-loaded TF-LPs on A549 cells and the inhibition of tumor spheroid growth was stronger compared with the effect of DOX-loaded lipid-coated PLGA-NPs and PLGA-NPs. In the in vivo component of the present study, TF-LP demonstrated the best inhibitory effect on tumor growth in the A549 tumor-bearing mice. It was concluded that TF-LP may be an efficient targeted drug-delivery system for lung cancer therapy.

Trans-[Ru(NO)Cl(cyclam)](PF6)2and [Ru(NO)(Hedta)] Incorporated in PLGA Nanoparticles for the Delivery of Nitric Oxide to B16–F10 Cells: Cytotoxicity and Phototoxicity

The immobilization and characterization of trans-[Ru(NO)Cl(cyclam)](PF6)2 (cyclam=1,4,8,11-tetraazacyclotetradecane), and [Ru(NO)(Hedta)] (Hedta=ethylenediaminetetraacetic acid) entrapped in poly(d,l-lactic-co-glycolic) acid (PLGA) nanoparticles (NP) using the double emulsification process is described. Scanning electron microscopy and dynamic light scattering revealed that the particles are spherical in shape, have a size distribution between 220 and 840 nm of diameter, and have a tendency to aggregate confirmed by a zeta potential between -3.2 and +3.5 mV. Using this method the loading efficiency was 26% for trans-[Ru(NO)Cl(cyclam)](PF6)2 and 32% for [Ru(NO)(Hedta)]. The release of the complexes from the NPs shows that cyclam-NP and Hedta-NP exhibited a two-phase exponential association release pattern, which was characterized by an initial complex burst during the first 24 h, followed by a slower release phase complex profile, due to a few pores observed in surface of nanoparticles using atomic force microscopy. The in vitro cytotoxic activity of the nitrosyl complexes in solution and incorporated in PLGA nanoparticles on melanoma cancer cells (cell line B16-F10) was investigated. The lower cytotoxicity of trans-[RuCl(cyclam)(NO)]2+ (12.4±2.6%) and [Ru(NO)(Hedta)] (4.0±2.7%) in solution compared to that of trans-[Ru(NO)(NH3)4py]3+ (46.1±6.4%) is consistent with the rate constant release of NO of these complexes (k-NO=6.2×10(-4) s(-1), 2.0×10(-3) s(-1), and 6.0×10(-2) s(-1), respectively); the cytotoxicities are also inhibited in the presence of the NO scavenger carboxy-PTIO. The phototoxicity of these complexes is due to NO release, which lead to 53.8±6.2% of cell death in the presence of trans-[Ru(NO)Cl(cyclam)](PF6)2 and 22.3±5.1% in the presence of [Ru(NO)(Hedta)]. The PLGA nanoparticles loaded with trans-[Ru(NO)Cl(cyclam)](PF6)2 and [Ru(NO)(Hedta)] exerted in vitro a reduced activity against melanoma cells when compared to the activity of complex in solution (nonentrapped in nanoparticles). Blank PLGA nanoparticles did not exhibit cytotoxicity. In the presence of light and of ruthenium nitrosyl complexes or cyclam-NP and Hedta-NP, B16-F10 cells displayed a considerable damage of the surface with rupture of the plasma membrane. This behavior is an indicative of the efficiency of the DDS to deliver the NO from the entrapped complex when photoinduced.

Co-encapsulation of human serum albumin and superparamagnetic iron oxide in PLGA nanoparticles: Part I. Effect of process variables on the mean size

PLGA (poly d,l-lactic-co-glycolic acid) nanoparticles (NPs) encapsulating magnetite nanoparticles (MNPs) along with a model drug human serum albumin (HSA) were prepared by double emulsion solvent evaporation method. This Part I will focus on size and size distribution of prepared NPs, whereas encapsulation efficiency will be discussed in Part II. It was found that mean hydrodynamic particle size was influenced by five important process variables. To explore their effects, a five-factorial, three-level experimental design and statistical analysis were carried out using STATISTICA® software. Effect of process variables on the mean size of nanoparticles was investigated and finally conditions to minimize size of NPs were proposed. GAMS™/MINOS software was used for optimization. The mean hydrodynamic size of nanoparticles ranged from 115 to 329 nm depending on the process conditions. Smallest possible mean particle size can be achieved by using low polymer concentration and high dispersion energy (enough sonication time) along with small aqueous/organic volume ratio.

Co-encapsulation of human serum albumin and superparamagnetic iron oxide in PLGA nanoparticles: Part II. Effect of process variables on protein model drug encapsulation efficiency

This study investigates encapsulation efficiency of model drug, encapsulated by magnetic poly d,l-lactic-co-glycolic acid (PLGA) nanoparticles (NPs). This is the following part of our preceding paper, which is referred in this paper as Part I. Magnetic nanoparticles and model drug human serum albumin (HSA)-loaded PLGA NPs were prepared by the double emulsion solvent evaporation method. Among five important process variables, concentration of PLGA and concentration of HSA in the inner aqueous phase along with their cross-effect had the strongest influence on the encapsulation efficiency. Encapsulation efficiency of nanoparticles ranged from 18% to 97% depending on the process conditions. Higher encapsulation efficiencies can be achieved by using low HSA and high PLGA concentrations. The optimization process, carried out by exact mathematical tools using GAMSTM/MINOS software makes it easier to find out optimum process conditions to achieve comparatively high encapsulation efficiency (e.g. 92.3%) for relatively small-sized PLGA NPs (e.g. 155 nm).

A modified double-emulsion method for the preparation of daunorubicin-loaded polymeric nanoparticle with enhanced in vitro anti-tumor activity

The encapsulation of hydrophilic drug in polymeric nanoparticles with high loading remains a challenge due to the rapid penetration of the drug to the external aqueous phase. In order to improve the encapsulation efficiency of daunorubicin (DNR) in poly(d,l-lactic-co-glycolic acid (PLGA) and poly(d,l-lactic acid) (PDLLA) nanoparticles, we fabricated a series of DNR-loaded nanoparticles using a modified double-emulsion solvent evaporation/diffusion method, which introduced a partially water-soluble organic solvent into the particle formation. The influence of various preparation parameters was investigated systematically, such as the ratio of organic solvent, the type of surfactant, the type of polymers and the molecular weight. Results showed that regular spherical PLGA nanoparticles with diameters of 200–300 nm could be produced with a remarkably high DNR encapsulation efficiency (>80%) and loading (6.5% (w/w)). Upon encapsulation, the sustained release of DNR could be controlled over 2 weeks. The results of FT-IR and DSC analysis indicated that the encapsulated DNR in polymeric nanoparticles was inclusion, not absorption. Furthermore, optimized DNR/PLGA nanoparticles showed a significant enhancement of cellular uptake, higher cytotoxicity against HL-60 cells compared with free DNR. These results were potentially useful for the nanoparticle formulation of hydrophilic chemotherapeutic drugs that require efficient delivery to cancer cells as well as sustained release at the specific site.

Insulin-Loaded PLGA Nanoparticles for Oral Administration: An &lt;I&gt;In Vitro&lt;/I&gt; Physico-Chemical Characterization

The aim of this work was to study poly(d,l-lactic-co-glycolic) acid (PLGA) nanoparticles--formulated by a modified solvent diffusion technique--applied as model nanocarriers for insulin in potential oral administrations. These nanostructures consisted of a blend matrix formed by PLGA copolymer and polyoxyethylene derivatives. Two types of blend formulations, PLGA:poloxamer (Pluronic F68) and PLGA:poloxamine (Tetronic T904), were analyzed, and the results compared to those obtained with pure PLGA nanoparticles. The work has been divided into two parts. (a) Firstly, the stability of the unloaded nanoparticles in simulated gastric and intestinal fluids was studied. Degradation studies reflected a strong interaction between the pure PLGA nanoparticles and the digestive enzymes. However, this interaction was considerably reduced in the blend formulations, although the PLGA:poloxamine system became colloidally unstable in the simulated gastric fluid. (b) Secondly, the effect of the net charge of the encapsulated macromolecule in the final properties of the blend formulations was studied by encapsulating insulin below and above its corresponding isoelectric point. The net charge of the encapsulated protein showed a clear effect in the final size of the nanoparticles, while the encapsulation efficiency was controlled by the polyoxyethylene derivative presents in the blend formulation. The obtained results show that those carriers formed with encapsulated insulin in PLGA-Pluronic F68 particles are capable, at least in vitro, to overcome the gastrointestinal barrier. Therefore, these nanocarriers seem to be appropriate for oral administration of insulin, although performing in vivo studies becomes necessary to corroborate such statement.

Chloramphenicol-incorporated poly lactide-co-glycolide (PLGA) nanoparticles: Formulation, characterization, technetium-99m labeling and biodistribution studies

Chloramphenicol-loaded (CHL) poly-d,l-lactic-co-glycolic acid (PLGA) nanoparticles (NPs) were prepared by emulsification solvent evaporation technique either by using polyvinyl alcohol (PVA) as emulsion stabilizer or polysorbate-80 (PS-80) as surfactant and characterised by transmission electron microscopy, zeta-potential measurements. The NPs were radiolabeled with technetium-99m (99mTc) by stannous reduction method. Labeling conditions were optimised to achieve high-labeling efficiency, in vitro and in vivo (serum) stability. The labeled complexes also showed very low transchelation as determined by DTPA challenge test. Biodistribution studies of 99mTc-labeled complexes were performed after intravenous administration in mice. The CHL-loaded PLGA NPs coated with PS-80 exhibited relatively high brain uptake with comparatively low accumulation in bone marrow to that of free drug and CHL-loaded PLGA NPs (PVA, used as emulsion stabilizer) at 24 h post injection time period. This indicates the usefulness of the above delivery system for prolonged use of the antibiotic.