Microencapsulation of a synbiotic into PLGA/alginate multiparticulate gels

Probiotic bacteria have gained popularity as a defence against disorders of the bowel. However, the acid sensitivity of these cells results in a loss of viability during gastric passage and, consequently, a loss of efficacy. Probiotic treatment can be supplemented using ‘prebiotics’, which are carbohydrates fermented specifically by probiotic cells in the body. This combination of probiotic and prebiotic is termed a ‘synbiotic’. Within this article a multiparticulate dosage form has been developed, consisting of poly(d,l-lactic-co-glycolic acid) (PLGA) microcapsules containing prebiotic Bimuno™ incorporated into an alginate–chitosan matrix containing probiotic Bifidobacterium breve. The aim of this multiparticulate was that, in vivo, the probiotic would be protected against gastric acid and the release of the prebiotic would occur in the distal colon. After microscopic investigation, this synbiotic multiparticulate was shown to control the release of the prebiotic during in vitro gastrointestinal transit, with the release of galacto-oligosaccharides (GOS) initially occurred over 6 h, but with a triphasic release pattern giving further release over 288 h. Encapsulation of B. breve in multiparticulates resulted in a survival of 8.0 ± 0.3 log CFU/mL cells in acid, an improvement over alginate–chitosan microencapsulation of 1.4 log CFU/mL. This was attributed to increased hydrophobicity by the incorporation of PLGA particles.

pH-sensitive and targeted PLGA-based drug delivery to colorectal cancer

Investigation on targeted PLGA based drug delivery system for the therapy of colorectal cancer. The results from in-vitro cell experiments indicated that prepared systems have potent cytotoxicity and high affinity to HT-29 cancer cells. Results were published on Biomedical Engineering and Informatics and ICONN conference proceeding.

Chitosan-modified PLGA nanoparticles with versatile surface for improved drug delivery

Shortage of functional groups on surface of poly(lactide-co-glycolide) (PLGA)-based drug delivery carriers always hampers its wide applications such as passive targeting and conjugation with targeting molecules. In this research, PLGA nanoparticles were modified with chitosan through physical adsorption and chemical binding methods. The surface charges were regulated by altering pH value in chitosan solutions. After the introduction of chitosan, zeta potential of the PLGA nanoparticle surface changed from negative charge to positive one, making the drug carriers more affinity to cancer cells. Functional groups were compared between PLGA nanoparticles and chitosan-modified PLGA nanoparticles. Amine groups were exhibited on PLGA nanoparticle surface after the chitosan modification as confirmed by Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy. The modified nanoparticles showed an initial burst release followed by a moderate and sustained release profile. Higher percentage of drugs from cumulative release can be achieved in the same prolonged time range. Therefore, PLGA nanoparticles modified by chitosan showed versatility of surface and a possible improvement in the efficacy of current PLGA-based drug delivery system.

Electrosprayed PLGA smart containers for active anti-corrosion coating on magnesium alloy Amlite

A novel self-healing system, consisting of poly(lactic-co-glycolic) acid (PLGA) porous particles loaded with a corrosion inhibitor, i.e. benzotriazole (BTA), has been successfully achieved via direct electro-spray deposition and subsequent epoxy spraying upon magnesium (Mg) alloy AMlite. The two-step process greatly simplified the multi-step fabrication of smart coatings reported previously. The PLGA particles demonstrate rapid response to both water and pH increase incurred by corrosion of Mg, ensuring instant and ongoing release of BTA to self-heal the protective functionality and retard further corrosion. Furthermore, nanopores in the PLGA–BTA microparticles, formed by the fast evaporation of dichloromethane during the electrospray process, also contribute to the fast release of BTA. Using Mg alloy AMlite as a model substrate which requires corrosion protection, potentiodynamic polarisation characterisation and scratch testing were adopted to reveal the anti-corrosion capability of the active coating.

Brain targeted PLGA nanocarriers alleviating amyloid-Β expression and preserving basal survivin in degenerating mice model

The chronic systemic administration of d-Galactose in C57BL/6J mice showed a relatively high oxidative stress, amyloid-β expression and neuronal cell death. Enhanced expression of pyknotic nuclei, caspase-3 and reduced expression of neuronal integrity markers further confirmed the aforesaid insults. However, concomitant treatment with the recombinant protein (SurR9-C84A) and the anti-transferrin receptor antibody conjugated SurR9-C84A (SurR9+TFN) nanocarriers showed a significant improvement in the disease status and neuronal health. The beauty of this study is that the biodegradable Food and Drug Administration (FDA) approved poly(lactic-co-glycolic acid) (PLGA) nanocarriers enhanced the biological half-life and the efficacy of the treatments. The nanocarriers were effective in lowering the amyloid-β expression, enhancing the neuronal integrity markers and maintaining the basal levels of endogenous survivin that is essential for evading the caspase activation and apoptosis. The current study herein reports for the first time that the brain targeted SurR9-C84A nanocarriers alleviated the d-Galactose induced neuronal insults and has potential for future brain targeted nanomedicine application.

Development of praziquantel-loaded PLGA nanoparticles and evaluation of intestinal permeation by the everted gut Sac model

Praziquantel has been shown to be highly effective against all known species of Schistosoma infecting humans. Spherical nanoparticles made of poly(D,L-lactide-co-glycolide) acid with controlled size were designed as drug carriers. Praziquantel, a hydrophobic drug, was entrapped into the polymeric nanoparticles with 30% (w/w) of theoretical loading. The nanoparticles size was approximately of 350 nm with 66% of encapsulation efficiency. The everted gut sac model shows to be efficient to evaluate the drug permeation through the intestinal membrane. The results show that free praziquantel presents 4-fold times more permeation than praziquantel-loaded PLGA nanoparticles and physical mixture. For this drug, in special, this result can be interesting, since the nanoparticulate system can behave as a drug reservoir and/or to have a more localized effect in intestinal membrane for a prolonged period of time, since great amounts of parasites can be usually found in the mesenteric veins.

Praziquantel-loaded PLGA nanoparticles: preparation and characterization

Nanoparticles containing praziquantel made of Poly (D,L-lactide-co-glycolide) were designed by an emulsion-solvent evaporation method. Two organic solvents were separately utilized as disperse phase: methylene chloride and ethyl acetate. The size of the particles prepared with the former solvent was bigger than the particles prepared with the latter. The entrapment efficiency was bigger when methylene chloride was used, 79.82% in comparison with 29.27% by using ethyl acetate. DSC and infrared studies showed that no strong chemical interaction between drug and polymer occurred. Release kinetics of praziquantel, used as a model drug, was governed not only by actual drug loading but also by particles size. The higher the drug content and the smaller the particle size resulted in faster drug release.

PLGA nanoparticles containing praziquantel: effect of formulation variables on size distribution

Praziquantel has been shown to be highly effective against all known species of Schistosoma infecting humans. Spherical nanoparticulate drug carriers made of poly(D,L-lactide-co-glycolide) acid with controlled size were designed. Praziquantel, a hydrophobic molecule, was entrapped into the nanoparticles with theoretical loading varying from 10 to 30% (w/w). This investigates the effects of some process variables on the size distribution of nanoparticles prepared by emulsion-solvent evaporation method. The results show that sonication time, PLGA and drug amounts, PVA concentration, ratio between aqueous and organic phases, and the method of solvent evaporation have a significant influence on size distribution of the nanoparticles. (C) 2004 Elsevier B.V. All rights reserved.

Phagocytosis of PLGA microparticles in rat peritoneal exudate cells: A time-dependent study

With the purpose of enhancing the efficacy of microparticle-encapsulated therapeutic agents, in this study we evaluated the phagocytic ability of rat peritoneal exudate cells and the preferential location of poly(D,L-lactide-co-glycolic acid) (PLGA) microparticles inside these cells. The microparticles used were produced by a solvent evaporation method and were characterized by dynamic light scattering (DLS), transmission electron microscopy (TEM), and scanning electron microscopy (SEM). Size distribution analysis using DLS and SEM showed that the particles were spherical, with diameters falling between 0.5 and 1.5 mu m. Results from cell adhesion by SEM assay, indicated that the PLGA microparticles are not toxic to cells and do not cause any distinct damage to them as confirmed by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay. Among the large variety of cell populations found in the peritoneal exudates (neutrophils, eosinophils, monocytes, and macrophages), TEM showed that only the latter phagocytosed PLGA microparticles, in a time-dependent manner. The results obtained indicate that the microparticles studied show merits as possible carriers of drugs for intracellular delivery.

Initial Development and Characterization of PLGA Nanospheres Containing Ropivacaine

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Single dose of a vaccine based on DNA encoding mycobacterial hsp65 protein plus TDM-loaded PLGA microspheres protects mice against a virulent strain of Mycobacterium tuberculosis

The high incidence of tuberculosis around the world and the inability of BCG to protect certain populations clearly indicate that an improved vaccine against tuberculosis is needed. A single antigen, the mycobacterial heat shock protein hsp65, is sufficient to protect BALB/c mice against challenge infection when administered as DNA vaccine in a three-dose-based schedule. In order to simplify the vaccination schedule, we coencapsulated hsp65-DNA and trehalose dimicolate (TDM) into biodegradable poly(DL-lactide-co-glycolide) (PLGA) microspheres. BALB/c mice immunized with a single dose of DNA-hsp65/TDM-1oaded microspheres produced high levels of IgG2a subtype antibody and high amounts of IFN-gamma in the supernatant of spleen cell cultures. DNA-hsp65/TDM-loaded microspheres were also able to induce high IFN-gamma production in bulk lung cells from challenged mice and confer protection as effective as that attained after three doses of naked DNA administration. This new formulation also allowed a ten-fold reduction in the DNA dose when compared to naked DNA. Thus, this combination of DNA vaccine and adjuvants with immunomodulatory and carrier properties holds the potential for an improved vaccine against tuberculosis.

Characterization of PLGA microparticles as a drug carrier for 3-ethoxycarbonyl-2H-benzofuro[3,2-f]-1-benzopyran-2-one. Ultrastructural study of cellular uptake and intracellular distribution

Here we describe the application of microparticles (MPs) for the delivery and release of the drug a benzopsoralen. We also evaluated the intracellular distribution and cellular uptake of the drug by using an encapsulation technique for therapeutic optimization. MPs containing the compound 3-ethoxycarbonyl-2H-benzofuro[3,2-f]-1-benzopyran-2-one (psoralen A) were prepared by the solvent evaporation technique, and parameters such as particle size, drug encapsulation efficiency, effect of the encapsulation process on the drug's photochemistry, zeta potential, external morphology, and < i > in vitro release behavior were evaluated. The intracellular distribution of MPs as well as their uptake by tissues were monitored. Size distribution studies using dynamic ligh scattering and scanning electron microscopy revealed that the MPs are spherical in shape with a diameter of 1.4 mu m. They present low tendency toward aggregation, as confirmed by their zeta potential (+10.6 mV). The loading efficiency obtained was 75%. As a consequence of the extremely low diffusivity of the drug in aqueous medium, the drug release profile of the MPs in saline phosphate buffer (pH 7.4) was much slower than that obtained in the biological environment. Among the population of peritoneal phagocytic cells, only macrophages were able to phagocytose poly-d,l-lactic-co-glycolic acid (PLGA) MP. The use of psoralen A in association with ultraviolet light (360 nm) revealed morphological characteristics of cell damage such as cytoplasmic vesiculation, mitochondria condensation, and swelling of both the granular endoplasmatic reticulum and the nuclear membrane. These results indicate that PLGA MP could be a promising delivery system for psoralen in connection with ultraviolet irradiation therapy (PUVA).

Identification of psoralen loaded PLGA microspheres in rat skin by light microscopy

Drug delivery systems involving the use of polymers are widely studied and discovery of biocompatible polymers has become the focus of research in this area. Psoralen loaded poly(DL-lactide-co-glycolide) (PLGA) microspheres to be used in PUVA therapy (psoralen and UVA irradiation (ultraviolet A, 320-400 nm) of psoriasis were identified in paraffin sections by histological analysis. The psoralen loaded PLGA microspheres were prepared using the solvent evaporation technique. They were spherical and possessed an external smooth surface as observed by scanning electron microscopy (SEM) analysis. This study describes a modification in the routine preparation of microsphere samples for examination by light microscopy. The changes involved fixative agents and/or stains allowing the identification of microspheres containing a non-fluorescent material. The preservation and identification of microspheres in tissues for histological processing in paraffin was greatly improved by these modifications as proven by our results. (c) 2007 Elsevicr Ltd. All rights reserved.

Thermoanalytical study of praziquantel-loaded PLGA nanoparticles

Polymeric nanoparticles have received great attention as potential controlled drug delivery systems. Biodegradable polymers has been extensively used in the development of these drug carriers, and the polyesters such as polylactic acid, polyglycolic acid and their copolymers as poly-lactide-co- glycolide are the most used, considering its biocompatibility and biodegradability. Thermal analysis techniques have been used for pharmaceutical substances for more than 30 years and are routine methods for screening drug-excipient interactions. The aim of this work is to use thermal analysis to characterize PLGA nanoparticles containing a hydrophobic drug, praziquantel. The results show that the drug is in an amorphous state or in disordered crystalline phase of molecular dispersion in the PLGA polymeric matrix and that the microencapsulation process did not interfere with the chemical structure of the polymer, mantaining the structural drug integrity.