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Optimization of Preparation and Characteristics of Ngf-PLGA Nanoparticles in Vitro

Author: MeiLin
Tutor: LongDaHong
School: Guangzhou Medical College
Course: Human Anatomy,Histology and Embryology
Keywords: Polylactic acid - polyglycolic acid copolymers Nerve Growth Factor Bovine serum albumin Nanoparticles Complex emulsion solvent evaporation method Orthogonal experimental design
CLC: TQ460.1
Type: Master's thesis
Year: 2010
Downloads: 81
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Abstract

As the global population aging, the central nervous system (Central nervous system, CNS) disease, more and more people's attention. Alzheimer's disease (Alzheimer's disease, AD) is a degenerative disease of the central nervous system clinical performance of a cognitive and memory function decline. The pathogenesis of AD is unclear, and the treatment is very limited, the effect is not ideal. Clinical rely mainly on cholinesterase inhibitors, NMDA receptor antagonists, as well as a variety of improved cerebral circulation drugs. However, these drugs can only slow the disease process, but can not stop or reverse the development of the disease. Laboratory studies found that the neurotrophic factor drugs to be effective against the disease progression and improve symptoms of AD. Nerve growth factor (Nerve growth factor, NGF), having a high biological activity of the protein and its receptor is ubiquitous in the human central and peripheral nervous system neurons. The main role of NGF nutrition and protect the nerve cells, restoration of damaged nerve cells and can promote nerve growth. Animal studies have found that for the treatment of Alzheimer's also has the effect of significant improvement in symptoms. Furthermore, the NGF isolated from different species of animal body having a high degree of homology, animal-derived NGF is equally suitable for human use, so NGF will become one of the most potential drug treatment of CNS disorders. However, due to the presence of the blood-brain barrier, NGF has been largely restricted in clinical applications. Them to take the early clinical intraventricular injection administered effectively, but is bound to increase the suffering of the patients and the risk of infection. And because NGF short half-life, as well as cerebrospinal fluid reflux and other reasons, the resulting drug is difficult to maintain the effective concentration in the brain, the drug utilization is very low. Therefore looking for a technology to increase the permeability of the blood-brain barrier of NGF increased NGF in the brain persistent role of NGF success key for clinical treatment. In recent years, with the development of nano-medicine technology, there have been articles reported the use of nano-drug carriers capable of carrying drugs penetrate the blood-brain barrier acts on the brain, NGF treatment of CNS diseases brought in a new direction. And 2005, the FDA approved the listing of albumin-bound paclitaxel nanoparticles injectable suspension (Paclitaxel, ABRAXANE), nano drug carrier security is guaranteed. Therefore, it is contemplated that NGF will be prepared as a sustained release nanoparticles to solve the NGF administration difficult problem of the treatment of CNS disorders. This thesis, bovine serum albumin (Albumin, BSA) and NGF as a model drug to polylactic acid - polyglycolic acid copolymer [Poly (lactic-co-glycolic acid), the PLGA as a drug carrier, using the prepared the complex emulsion solvent evaporation method polylactic acid - polyglycolic acid nanoparticles of the wrapped bovine serum albumin (BSA-PLGA-NPs) and wrapped in the polylactic acid - poly glycolic acid nanoparticles (NGF-PLGA-NPs) of the nerve growth factor through the nano-size analyzer to measure the overall average particle size and particle size distribution, surface morphology by scanning electron microscopy, encapsulation efficiency was measured using the BCA method and ELISA using orthogonal design to optimize the preparation process, and the the two nanoparticles drug release behavior study and comparison, the final nano drug carrier preparation process for this lab. Conclusion: 1. Single factor analysis showed that the PVA concentration increased, the average particle size of BSA-PLGA-NPs decreases; ultrasound time, the average particle size decreases; of PLGA increased use of the average particle size increases; BSA dosage and within the water phase volume average particle size had no significant effect. Orthogonal experimental design and analysis of variance, PVA concentration and ultrasonic time on the average particle size is not significant, but have a significant impact on the encapsulation efficiency PVA concentration increased, the encapsulation efficiency increases; ultrasound Time extension package The closure rate is also increased. But the amount of the PLGA particle size and encapsulation efficiency have significant impact, the increased use of the particle size increases, higher encapsulation efficiency. The larger nanoparticles smaller particle size based on the encapsulation efficiency the final confirmation optimization prescription PVA concentration of 0.7%, ultrasonic time 20 min of PLGA dosage of 25 mg. 3 in order to optimize the prescription for the standard, prepared BSA-PLGA-NPs minimum average particle size of 219 nm, the encapsulation efficiency was 44.7%. Minimum to the average particle size of the optimized formulation was prepared NGF-PLGA-NPs at 243 nm, the encapsulation efficiency was 45.2%. The average particle diameter of less than 300 nm, the encapsulation efficiency is greater than 40% of the protein polypeptide can be prepared with PLGA as material nanoparticle drug system. Also shows that the BSA as a model drug to explore the the NGF Nanoparticles process of experimental design is effective, but also has good repeatability. BSA-PLGA-NPs and NGF-PLGA-NPs in vitro release mechanism, indicating that both the initial burst release phase of sustained-release and post-release in vitro is divided into two stages. The burst release is directly dissolved and diffused into the release medium in the initial surface of the protein adsorbed on the nanoparticles. The controlled release reason is the protein that is located inside of the nanoparticles with the gradual degradation of the PLGA skeleton slowly released. Using optimized conditions for preparation of BSA-PLGA-NPs in 2 to 28 days of the release curve fitted with Higuchi equation Q = 8.31t1 / 2 43.60 (R2 = 0.982). NGF-PLGA-NPs due to the influence of protein denaturation, sustained release time only lasted 14 days, within 2 to 14 days of the release curve fitting with Higuchi equation Q = 9.24t1 / 2 42.56 (R2 = 0.996).

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