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Studies on Braintide-PLGA Microspheres

Author: JiYaJu
Tutor: XuZuo
School: Shenyang Pharmaceutical University
Course: Pharmacy
Keywords: Brain peptide Lactic acid - glycolic acid copolymer (PLGA) Microspheres Sustained-release W1/O/W2 double emulsion - solvent evaporation method In vivo correlation Biocompatibility
CLC: R94
Type: Master's thesis
Year: 2006
Downloads: 28
Quote: 0
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Abstract


In this paper, a treatment for senile dementia (Alzheimer's disease), synthetic small molecule peptides - brain peptide as a model drug, lactic acid - glycolic acid copolymer (polylactic-co-glycolic acid, PLGA) microspheres skeleton material by W 1 / O / W , 2 complex emulsion - solvent evaporation prepared brain peptide-PLGA injection microspheres microspheres in vitro and in vivo characteristics. First, the establishment of the RP-HPLC method for the determination of brain peptide content, microsphere drug loading and drug encapsulation efficiency. Method specificity, linearity, accuracy and reproducibility of sample analysis are in line with requirements, and can be used for drug prescription screening and evaluation of pharmaceutics. Before prescribing research work, the measurement of a brain peptide in a variety of organic solvents in the apparent solubility and partition coefficient, investigated the stability of the solution of the brain peptide. The results indicate that the brain the apparent solubility of the peptide in an organic solvent of dichloromethane (DCM), ethyl acetate (EA) is low, the distribution coefficient is small (<3.0 × 10 -2 ), suitable for use W 1 / O / W 2 the multiple emulsion - solvent evaporation method microsphere. Acidic solution, the stability of the brain peptide is superior to an alkaline solution; EDTA stabilizer can significantly improve the stability. The W 1 / O / W 2 complex milk - solvent evaporation method brain peptide-PLGA microspheres, namely: the drug is dissolved in an aqueous solution containing bovine serum albumin with acetic acid to adjust the pH 5, for the internal aqueous phase; of PLGA was dissolved in DCM-EA mixture (DCM: EA = 3:2, v / v), as an oil phase; inner water phase added to the oil phase, mixing, ultrasound oscillation so that the formation of colostrum; colostrum added to the aqueous polyvinyl alcohol, strong mechanical dispersion was W 1 / O / W 2 -type double emulsion; slow stirring play The dry organic solvent, microspheres cured, followed by filtration, washing, vacuum drying was brain peptide-PLGA microspheres. For the evaluation of particle size and size distribution of the microspheres, drug encapsulation efficiency indicators, a single factor, the initial prescription and technological factors on the blank PLGA microspheres and brain peptide-PLGA microspheres nature. The W 1 / O / W , 2 double emulsion - solvent evaporation method can obtain an average particle size of 20-30μm, drug encapsulation efficiency was 90% of the brain peptide - PLGA microspheres. The effects of a prescription law of microspheres in vitro drug release. The results show that the brain peptide-PLGA microspheres in vitro drug release was staged release, that the initial 24h burst release (Higuchi equation); followed by the release of drug steady rate close to zero-order kinetics process . Mixture was adjusted to an inner aqueous phase of the composition of PLGA concentration or using a variety of models of PLGA as a skeleton material, can effectively control the burst release of the drug, 24h within release amount is less than 20%. Mice in vivo studies show that the brain peptide-PLGA microspheres in vivo drug release and in vitro release profile similar to in vivo correlation good. The histological examination confirmed the injection site of administration, the brain peptide-PLGA microspheres have good histocompatibility. Were prepared suitable average particle diameter, the drug encapsulation efficiency, in vitro sudden release lower brain peptide-PLGA microspheres, the microspheres dispersed in a suitable medium, can be easily injected to the subcutaneous or intramuscular. The preparation of the microspheres can release the drug over a longer period continued in vivo correlation has good histocompatibility.

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