國家衛生研究院 NHRI:Item 3990099045/9651

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Title:	Ultrasound-triggered release of model drugs in hydrogels
Authors:	Wu, CH;Sun, MK;Shih, TT;Chen, WS
Contributors:	Institute of Biomedical Engineering and Nanomedicine
Abstract:	OBJECTIVES:In biological systems, episodic release of bioactive compounds may elicit different effects from constant rate of release. For example, once-daily administration of pharmacological doses of parathyroid hormone has a bone anabolic effect, while continuous administration is detrimental for the skeleton due to stimulation of one resorption. Conventional drug delivery systems allow approximate spatial localization of cues depending on polymer degradation and passive diffusion, but are unable to control release rates temporarily. In contrast, “on-demand” release systems which based on polymers or materials activated by external stimuli may provide such temporal flexibility and are beginning to be applied in the clinical setting. The current study aims at exploring the accelerating release rate of bovine serum albumin (BSA) embedded in the N-isopropylacrylamide (NIPAM) -based hydrogel in response to temperature rise provided by ultrasound (US) exposure with energy in therapeutic ranges. METHODS: The NIPAM-based reusable hydrogel phantoms were fabricated by crosslinking copolymerization of NIAPM and N,N'-methylenebisacrylamide (MBAm) with the ddition of acrylic acid (AAc) to adjust the cloud point so that it fell in the emperature range of biological significance (37oC in this study). Hydrogels, before set, were mixed with BSA and added into a 6-well culture plate before heating by either water bath or US (1 MHz, 30% duty cycle, 3 W/cm2) for a certain period of time. The ability of BSA release from hydrogels was tested in various conditions including (1) different NIAPM (1, 2 and 3 g) and MBAm (0.02 to 0.10 g) compositions, (2) different target temperature from 25 to 45oC, and (3) water bath heating or ultrasound exposure (both thermal and mechanic effects). Moreover, the icrostructure of the hydrogel below and above the cloud point was examined by electronic microscopy.RESULTS:With the same MBAm amount, release of BSA reduced when NIPAM increased. With the same NIAPM amount, release of BSA increased with the increase of MBAm (Figure 1). Both water bath heating and US exposure induced BSA release and is temperature dependent, but significantly more release was induced by US exposure (Fig. 2). At temperature below the cloud point, the hydrogel (NIPAM/MBAm=1 g/ 0.02 g) is transparent in colour and shows dense microstructure with small pores. When heated above the cloud point, the whitish hydrogel shows pores of increased sizes.
Date:	2016-03
Relation:	International Society for Therapeutic Ultrasound (ISTU). 2016 Mar:410-412.
Link to:	http://www.istu.org/events/ann2016/abstractsBook.pdf
Appears in Collections:	[Others] Conference Papers/Meeting Abstract

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