Type of Document Master's Thesis Author Li, Jingyan Author's Email Address firstname.lastname@example.org URN etd-10242012-145420 Title Surface-modified PLGA Nanoparticles for Targeted Drug Delivery to Neurons Degree Master of Science in Biological & Agricultural Engineering (M.S.B.A.E.) Department Biological & Agricultural Engineering Advisory Committee
Advisor Name Title Sabliov, Cristina M Committee Chair Zheng, Jolene Committee Co-Chair Hayes, Daniel Committee Member Laine, Roger A Committee Member Keywords
- drug delivery
Date of Defense 2012-10-18 Availability unrestricted AbstractThe blood-brain barrier (BBB), which protects the central nervous system (CNS) from unnecessary substances, is a challenging obstacle in the treatment of CNS disease such as Parkinsonís Disease (PD). Many therapeutic agents such as hydrophilic and macromolecular drugs cannot overcome the BBB. One promising solution is the employment of polymeric nanoparticles (NPs) such as poly (lactic-co-glycolic acid) (PLGA) NPs as drug carrier. Over the past few years, significant breakthroughs have been made in developing suitable poly (lactic-co-glycolic acid) (PLGA) and poly (lactic acid) (PLA) nanoparticles for drug delivery across the BBB.
Recent advances on PLGA/PLA NPs enhanced neural delivery of drugs were reviewed in the second chapter. Both in vitro and in vivo studies were included. In these papers, enhanced cellular uptake and therapeutic efficacy of drugs delivered with modified PLGA/PLA NPs compared to free drugs or drugs delivered by unmodified PLGA NPs was shown; no significant in vitro cytotoxicity was observed for PLGA NPs and PLA NPs. Surface modification of PLGA/PLA NPs by coating with surfactants/polymers or covalently conjugating with targeting ligands has been confirmed to enhance drug delivery across the BBB. Most unmodified PLGA NPs showed low brain uptake (<1%), which confirms the safety of PLGA/PLA NPs used for other purposes than treating CNS diseases.
For the second part of the study, wheat germ agglutinin (WGA), a lectin was conjugated to PLGA nanoparticles (PLGA-tWGA NPs, 221 nm) to improve DAergic neuron delivery in C.elegans. PLGA-tWGA NPs did not show a significant effect on pumping rate and life span of C. elegans at low concentration (<3 mg/ml). Fluorescent studies of GFP-DAergic neurons revealed that area of GFP-DAergic neurons of worms treated with high concentrations PLGA-tWGA NPs (>3mg/ml) was significantly decreased. Number and mean intensity of GFP-DAergic neurons also decreased, but no significant difference was found compared with control group. Co-localization of the fluorescent particles with the GFP-DAergic neurons of treated worms proved targeting property of PLGA-tWGA nanoparticles to DAergic neurons. Enhanced targeted delivery of PLGA-tWGA NPs to neurons compared with tWGA and PLGA-t NPs made PLGA-tWGA NPs potential targeted neural delivery systems for the treatment of PD.
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