Preparation and characterization of melittin-loaded poly (DL-lactic acid) or poly (DL-lactic-co-glycolic acid) microspheres made by the double emulsion method.
ABSTRACT The water soluble peptide, melittin, isolated from bee venom and composed of twenty-six amino acids, was encapsulated in poly (DL-lactic acid, PLA) and poly (DL-lactic-co-glycolic acid, PLGA) microspheres prepared by a multiple emulsion [(W1/O)W2] solvent evaporation method. The aim of this work was to develop a controlled release injection that would deliver the melittin over a period of about one month. The influence of various preparation parameters, such as the type of polymer, its concentration, stabilizer PVA concentration, volume of internal water phase and level of drug loading on the characteristics of the microspheres and drug release was investigated. It was found that the microspheres of about 5 microm in size can be produced in high encapsulation (up to 90%), and the melittin content in the microspheres was up to 10% (w/w). The drug release profiles in vitro exhibited a significant burst release, followed by a lag phase of little or no release and then a phase of constant melittin release. The type of polymer used was a critical factor in controlling the release of melittin from the microspheres. In this study, the rate of peptide release from the microspheres correlated well with the rate of polymer degradation. Moreover, melittin was released completely during the study period of 30 days, which agreed well with the polymer degradation rate.
SourceAvailable from: Himansu Sekhar Nanda[Show abstract] [Hide abstract]
ABSTRACT: Growth factors are powerful therapeutics that control cell function by modulating cellular activities such as cell proliferation, migration and gene expression. In tissue engineering, it is important to keep the bioactivity of these labile molecules for an optimal duration in 3D microenvironment. Porous scaffolds can provide structural support as well as a functional platform for release of these drugs in a controlled and regulated manner. Controlled and local release of these cell inductive molecules from porous scaffolds can provide an efficient strategy to control the complex and dynamic regulation of cellular processes in 3D microenvironment and can improve the regeneration potential of engineered scaffolds. Technology involving spatial localization of these drugs via carrier based system such as drug delivery devices (DDS) made from natural and synthetic polymers is considered as one of the effective tools to develop appropriate porous scaffolds with controlled release function. Growth factor loaded biodegradable microbeads prepared from synthetic and natural polymers can be promising in the area of tissue engineering. The use of biodegradable microbeads can be expected to protect the biological activity of these labile molecules and thus can be able to avoid the rapid clearance. The technology can also be useful to release the molecule exactly at the local microenvironment in a controlled and regulated manner in a therapeutic limit. The objective of this research is to prepare a few kinds of such bioactive porous scaffolds with controlled release function for application in cartilage, skin and bone tissue engineering. Porous scaffolds were prepared by freeze drying method and pore structure was introduced and controlled using ice particulates or ice-collagen particulates of controlled diameters. Controlled release function was introduced via biodegradable microbeads of synthetic polymer, poly lactic-co-glycolic acid (PLGA), or natural polymer, collagen. In 1st and 2nd parts of the work, insulin loaded PLGA microbead functionalized collagen porous scaffolds with controlled pore structures were prepared and investigated for their application in cartilage and skin tissue engineering. In 3rd part of the work, dexamethasone loaded collagen microbead functionalized poly(L-lactide) (PLLA)-collagen hybrid scaffolds with controlled pore structures were prepared as an osteoinductive platform for bone tissue engineering.07/2014, Degree: Doctorate in Materials Science and Engineering, Supervisor: Professor Guoping Chen
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ABSTRACT: Cathelicidin-BF-30 (BF-30), a water-soluble peptide isolated from the snake venom of Bungarus fasciatus containing 30 amino acid residues, was incorporated in poly(D,L-lactide-co-glycolide) (PLGA) 75∶25 microspheres (MS) prepared by a water in oil in water W/O/W emulsification solvent extraction method. The aim of this work was to investigate the stability of BF-30 after encapsulation. D-trehalose was used as an excipient to stabilize the peptide. The MS obtained were mostly under 2 µm in size and the encapsulation efficiency was 88.50±1.29%. The secondary structure of the peptide released in vitro was determined to be nearly the same as the native peptide using Circular Dichroism (CD). The ability of BF-30 to inhibit the growth of Escherichia coli was also maintained. The cellular relative growth and hemolysis rates were 92.16±3.55% and 3.52±0.45% respectively.PLoS ONE 06/2014; 9(6):e100809. DOI:10.1371/journal.pone.0100809 · 3.53 Impact Factor
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ABSTRACT: To develop a bio-assay for measuring long-term bioactivity of released anti-inflammatory compounds and to test the bioactivity of celecoxib (CXB) and triamcinolone acetonide (TA) released from a new PLGA-based microsphere platform.Pharmaceutical Research 08/2014; DOI:10.1007/s11095-014-1495-z · 3.95 Impact Factor