ELECTROSPUN PLGA MICROFIBERS FOR LOCALIZED DELIVERY OF SMALL MOLECULES TO INDUCE BROWN ADIPOGENESIS
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Date
2014-05-05
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Johns Hopkins University
Abstract
Obesity and its related disorders have been on the rise in the last few decades. Current prescribed treatments range from diet and physical activity for low risk patients to pharmacological intervention and surgical procedures for higher risk patients. In the past few years, with the discovery of its presence in adult humans, brown adipose tissue has emerged as an interesting tool for reducing the risk of developing obesity or improving weight reduction in overweight or obese individuals. This study aims to create a system to deliver drugs specifically to white fat pads to increase brown fat differentiation, thus increase overall energy expenditure and improve energy metabolism in obesity and other metabolic disorders. The designed model system encapsulates rosiglitazone, a small molecule anti-diabetic drug, within electrospun poly(D,L-lactide-co-glycolide) (PLGA) microfibers. Drug release is sustained over a period of 35 days from microfibers with 0.5% w/w rosiglitazone loaded. In vitro experiments with the microfibers in a Transwell system demonstrate that 0.5% rosiglitazone was an optimal concentration for stimulating brown adipocyte differentiation. Furthermore, the rosiglitazone released from the microfibers was able to stimulate differentiation of white adipose-derived stem cells towards a brown adipocyte lineage. These results provide promising steps towards developing a therapy to create a localized depot of brown fat in situ that can be easily administered in the clinic to supplement current obesity treatment and prevention techniques.
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Keywords
Brown fat, localized delivery, rosiglitazone, PLGA