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Studies on Preparation and Bioavailability of Paclitaxel-loaded Poly (D,L-lactide-co-glycolide) Nanoparticles for Oral Administration

Author: JiShunLi
Tutor: GeYanRu；JinYi
School: Jiangsu University
Course: Pharmacy
Keywords: Paclitaxel Polylactide glycolide copolymer Nanoparticles Caco-2 cells In the intestinal absorption Bioavailability
CLC: R943
Type: Master's thesis
Year: 2010
Downloads: 655
Quote: 4
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Abstract

Of Taxol (Paclitaxel TAX) are antineoplastic agents, has been widely used in clinical practice, especially for breast cancer, ovarian cancer therapeutic effect is obvious. Because of its poor water solubility, the clinical use of paclitaxel in the paclitaxel injection rely polyoxyethylene castor oil (CremophorEL) and absolute ethanol to a 1:1 mixture of stable and dissolved. Polyoxyethylene castor oil can promote the release of histamine, a common cause of severe allergic reactions and other adverse reactions. In order to solve the above problems, this study does not contain Cremophor EL and can improve the formulation of paclitaxel bioavailability Points. Paclitaxel was prepared oral nanoparticle delivery system, not only to reduce side effects and increase its stability, and easy to store and transport. This article was prepared by paclitaxel nanoparticles (TAX-NPs) to optimize the formulation and preparation process, and its in vitro and in vivo evaluation. The main contents and results are as follows: established paclitaxel samples determined by HPLC method, its linear range, precision, recovery, and results show that the method meets the analysis requirements. Investigated the prescription to the biodegradable polymer - polylactide glycolide ester copolymer (PLGA) as a carrier, the use of emulsification - dispersion prepared Tax-NPs; particle size of the nanoparticles and the encapsulation rate of Evaluation Index its technological factors on the quality of the preparations; basic properties of the TAX-NPs, in vitro stability and release characteristics were investigated; differential scanning calorimetry (DSC) and X-ray powder diffraction (XRD) analysis of paclitaxel nanoparticles in the presence of state, TAX-NPs of average particle size (99 ± 7.6) nm, and zeta potential (78.3 ± 5.87) mV, encapsulation efficiency and drug loading (56.99 ± 0.29)% and ( 7.04 ± 0.13)%. Freeze-dried TAX-NPs in placed at 4 ° C for 6 months and good stability. DSC and XRD showed that the the TAX molecular form is wrapped in nanoparticles. TAX-NPS at two different pH values ??of PBS release in vitro release medium to simulate the in vivo environment, under conditions of low pH value, the more, the faster the drug release, the drug-loaded nanoparticles in the tumor environment acidic under the anti-tumor effect is very favorable. Study Caco-2 cells uptake of nanoparticles and their impact factors, to evaluate the feasibility of such nanoparticles as carriers of oral anticancer drugs. Fluorescent probe coumarin by wrapping a hydrophobic -6 (Coumarin-6, Cou-6) labeled nanoparticles Cou-6 using a fluorescence microplate reader detecting intracellular fluorescence intensity, to study particle size, incubation time, nano grain concentration, the surface properties of nanoparticles on Caco-2 cell uptake of nanoparticles. Using laser scanning confocal microscopy Caco-2 cell uptake of nanoparticles. Compared with polyvinyl alcohol (Polyvinyl alcohol, PVA) do emulsifier nanoparticles didodecyldimethylammonium bromide (Didodecyldimethyl ammonium bromide, DMAB) as emulsifier nanoparticles prepared by a significant increase in Caco- 2 cell uptake of nanoparticles and cells to a particle size of about 100 nm nanoparticles highest uptake. The results prove that nanoparticles can be absorbed into the bloodstream through the gastrointestinal tract administration. 3 in rat intestine absorption kinetics experiments, paclitaxel nanoparticles and their bulk drugs absorption in the intestine, absorption kinetics equations were: The paclitaxel nanoparticles LNX _residual = lnX ₀ -0.154 × t; paclitaxel API: the lnx _remaining = lnx ₀ -0.0023 × t, the correlation coefficient r were 0.9460 and 0.9102. Both absorbent having a significant difference (P <0.05), paclitaxel nanoparticles in the intestinal absorption rate constant was significantly greater than the paclitaxel API. 4. Paclitaxel plasma concentration method. Chromatographic conditions: column: a Diamonsil C ₁₈ column (250mm × 4.6mm, 5μm); mobile phase: acetonitrile / water (47:53, v / v); column temperature: 30 ℃; detection wavelength: 227nm; flow rate: 1.0ml/min; injection volume: 20 ul. High, medium and low concentrations recoveries were 91.23%, 92.68%, 89.38%. Day RSD were 3.81%, 3.49%, 2.89%, day RSD were 5.12%, 4.59%, 3.48%. The limit of quantitation was 0.02μg/ml. Created method is suitable for the determination of paclitaxel plasma concentration. Healthy SD rats as subjects, paclitaxel injection for the reference formulation, using randomized controlled study nanoparticles in vivo bioavailability. The experimental results show that the paclitaxel nanoparticles absolute bioavailability of 19.5%, transmission paclitaxel nanoparticle drug system to promote the absorption of paclitaxel to improve the oral bioavailability.

Studies on Preparation and Bioavailability of Paclitaxel-loaded Poly (D,L-lactide-co-glycolide) Nanoparticles for Oral Administration

Abstract

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