Category ME L11 Dendrimer-Dexamethasone Conjugates/Nanodevices for Targeted

Delivery

Abstract Since the discovery and development of drugs is an expensive and

tedious process, drug delivery systems are becoming increasingly

popular. Dendrimers are repeatedly branched synthetic polymers with

well-defined spherical structure, tailored surface properties, nanometer

scale size (~5-10 nm), high degree of molecular uniformity, and ability to

deliver drugs intracellularly. Since these surface functional groups can be

used to covalently attach imaging agents, drugs, or targeting ligands for

targeted delivery or controlled release, dendrimer nanodevices can be

effective delivery vehicles.



The novel idea behind this study was to develop and characterize a small

dendrimer-dexamethasone conjugate for delivery of dexamethasone in

order to minimize systemic effects and increase efficacy at the targeted

site. Dexamethasone, a synthetic member of the glucocorticoid class of

steroid hormones and an anti-inflammatory and immunosuppressant drug,

was conjugated to Generation 4 polyamidoamine (PAMAM) dendrimers

using a coupling reaction with PyBOP as the coupling reagent. The

synthesized conjugate was characterized using Nuclear Magnetic

Resonance Spectroscopy (NMR), High Performance Liquid

Chromatography (HPLC), and Matrix-assisted Laser Desorption Time-of-

Flight mass spectroscopy (MALDI-TOF). Since it is often challenging to

prepare delivery systems that can release the drugs within the target

tissue in a predetermined manner, drug release mechanisms and profiles in

conditions that these conjugates observe were understood to allow for a

more accurate prediction of their in vivo efficacy.



Such an unique conjugate would serve as an optimal transport vehicle for

delivering dexamethasone to specific tissues, thus providing treatments to

the body in a predetermined fashion. This vehicle could eventually be

utilized in patients with ocular diseases, such as macular degeneration or

diabetic retinopathy, as well as potentially any other disease (including

cancer and inflammation) in order that patients’ lives would be significantly

improved.

Bibliography http://www.nlm.nih.gov/medlineplus/eyediseases.html
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