Access Type

Open Access Dissertation

Date of Award

January 2011

Degree Type

Dissertation

Degree Name

Ph.D.

Department

Chemical Engineering and Materials Science

First Advisor

Rangaramanujam M. Kannan

Abstract

Dendrimers are ideal materials to be used in the emerging field of nanomedicine. Their nanoscale size and high density of functional groups on their peripheries allow them to be used for various biomedical applications. This work exploits dendrimers as drug delivery vehicles and a versatile platform for capturing biomarkers with improved sensitivity and specificity. Hydroxyl terminated poly(amidoamine) dendrimer (PAMAM-OH) was modified with a linker having amine group at the end and conjugated to two drugs, erythromycin (EM) and allopregnanonolne, respectively and evaluated in vitro. Both drugs were provided with a linker having carboxylic group required for conjugation reaction with dendrimer. The release rate of the drugs from the conjugates in PBS buffers at pH 7.4 for EM and pH 2.1 for allopregnanolone were evaluated by reverse phase HPLC (RP-HPLC) analysis. EM released quite fast, about 90% of the drug was released within 10 hours and completed within 20 hours, while allopregnanolone released in slower manner, about 90% of the drug was released within 9 days. Dendrimer-EM conjugate was not cytotoxic and was significantly efficacious in inhibiting the nitrite production compared to free drug. The inhibition of bacterial growth by dendrimer-EM conjugate was comparable to free EM. Combined with the intinsinic properties of dendrimers, these nanodevices could lead to improved in vivo efficacy. PAMAM-OH was successfully used for the development of a solid phase bio-sensing platform. The ELISA plate was modified first with polyethylene-glycol (PEG) and then PAMAM-OH was immobilized. A capture antibody was oxidized and covalently attached to dendrimer-modified ELISA plate which gives antibody favorable orientation for the antigen binding sites toward the analyte. The dendrimer modified plate showed enhanced sensitivity and the detection limit for TNF-á was found to be 0.48 pg/mL, which is significantly better than the commercially available ELISA kit. The selectivity of the dendrimer-modified ELISA plate was examined by studying TNF-á in a mixture of cytokines which gave similar results. Dendrimer-modified ELISA plate provides a greater opportunity for the detection of a wide range of cytokines and biomarkers.

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