Targeted Drug Delivery To Human Aortic Smooth Muscle Cells Using Biodegradable Nanoparticles

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Title: Targeted Drug Delivery To Human Aortic Smooth Muscle Cells Using Biodegradable Nanoparticles
Author: Specht, Danyel
Abstract: Restenosis is a common problem that can occur in angioplasty patients . In order to reduce the restentosis rate , various treatments such as glucocorticoids and drug eluting stents have been used for angioplasty patients . However , their limitations include the inefficient delivery of drugs to inhibit smooth muscle cell proliferation , a major cause of restenosis . Therefore , we propose the use of biodegradable nanoparticles as a drug delivery system for transporting a therapeutic agent to human aortic smooth muscle cells (HASMC ) to prevent their proliferation . In this study the glucocorticoid dexamethasone (DEX ) was chosen as the therapeutic agent . A biodegradable polymer , poly (D ,Llactide -co -glycolide ) (PLGA ) was used to formulate the nanoparticles through the evaporative emulsion technique . The mean nanoparticle diameter was found to be approximately 130 nm with a range of 88 -190 nm . Various uptake studies were conducted to determine the optimal nanoparticle incubation time , dosage , and biocompatibility . Based on the results it was concluded that PLGA nanoparticles were biocompatible to HASMC , and the optimal time and concentration for cellular uptake were 4 hours and 800 µg /ml , respectively . Drug release studies indicated PLGA nanoparticles produced a sustained release of DEX . Over a period of 3 weeks about 12 % of DEX was released from the nanoparticles . HASMC proliferation studies conducted using DEX indicated that cellular proliferation is significantly reduce when using a DEX concentration of 100 nM or higher . Additional studies were performed to compare our DEX encapsulated nanoparticles against non -encapsulated DEX . The comparative studies suggested that PLGA nanoparticles encapsulated with DEX were more sufficient than free DEX (DEX added directly in the cell media ) to inhibit HASMC proliferation . Lastly , the nanoparticles were ligand conjugated to PDGF -BB and compared against non -targeted nanoparticles . It was evident that the cellular uptake on non -targeted nanoparticles was significantly less than that of PDGF -BB targeted particles . Our results suggest that PDGF -BB peptide conjugated PLGA nanoparticles can be used as a targeted and controlled drug delivery vehicle to reduce the restenosis rate for patients who are undergoing cardiovascular interventions .
URI: http : / /hdl .handle .net /10106 /1106
Date: 2008-09-17


Targeted Drug Delivery To Human Aortic Smooth Muscle Cells Using Biodegradable Nanoparticles. Available electronically from http : / /hdl .handle .net /10106 /1106 .

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