Formulation and in vitro-in vivo evaluation of black raspberry extract-loaded PLGA/PLA injectable millicylindrical implants for sustained delivery of chemopreventive anthocyanins.
Formulation and in vitro-in vivo evaluation of black raspberry extract-loaded PLGA/PLA injectable millicylindrical implants for sustained delivery of chemopreventive anthocyanins.
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DOI：
10.1007/s11095-009-0038-5
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发表时间：
2010-04
影响因子：
3.7
通讯作者：
Schwendeman, Steven P.
中科院分区：
文献类型：
--
作者：
Desai, Kashappa Goud H.;Olsen, Karl F.;Mallery, Susan R.;Stoner, Gary D.;Schwendeman, Steven P.
关键词：
本研究的目的是配制和评价冻干黑树莓（FBR）乙醇提取物（RE）负载聚（DL-乳酸-羟基乙酸）（PLGA）和聚（DL-乳酸）（PLA）可注射毫林素植入剂，用于持续递送化学预防性FBR花青素（矢车菊素-3-桑布双糖苷（CS），矢车菊素-3-葡萄糖苷（CG）和矢车菊素-3-芸香糖苷（CR））。通过质谱法和HPLC法对RE中的CS、CG和CR进行鉴别和定量。采用捏合法制备了RE：三乙酰基-β-环糊精（TA-β-CD）包合物（IC），并用X射线衍射（XRD）、核磁共振（NMR）和紫外-可见光谱（UV-Vis）对其进行了表征。RE或RE：TA-β-CD IC负载的PLGA或PLA植入物通过溶剂挤出法制备。分别在磷酸盐缓冲盐水Tween-80（pH 7.4，37 ℃）中和雄性Sprague-Dawley大鼠皮下给药后进行体外和体内控释研究。通过HPLC在520 nm处定量花青素苷。RE中CS、CG和CR的含量分别为0.2、1.5和3.5wt%。花青素苷在溶液中的化学稳定性被确定为pH依赖性，并且它们的降解速率随着pH从2.4增加到7.4而增加。负载有5或10wt%RE的PLGA/PLA毫林替尼植入物表现出高的初始突释和短的花青素苷释放持续时间（1天和14天后分别释放35-52和80- 100%CG + CR）。花青素苷快速释放的原因与RE的大非花青素苷级分的高渗透压组分相关的较高的聚合物吸水率和孔隙度有关。XRD、1H NMR和UV-可见光谱表明，RE的非花色素苷组分分子与TA-β-CD形成IC，降低了RE的亲水性。与疏水载体TA-β-CD形成的IC提供了FBR花青素苷在1个月内的更好的体外/体内持续释放（分别为16-24和97- 99%CG + CR释放，从20wt%RE：TA-β-CD IC/PLA植入物1天和28天后），这是由于降低的聚合物吸水率和孔隙率。载RE：TA-β-CD IC的PLA可注射毫林匹林植入剂是用于1个月缓慢和连续递送化学预防性FBR花青素的最佳剂型。
The objective of this study was to formulate and evaluate freeze-dried black raspberry (FBR) ethanol extract (RE) loaded poly(DL-lactic-co-glycolic acid) (PLGA) and poly(DL-lactic acid) (PLA) injectable millicylindrical implants for sustained delivery of chemopreventive FBR anthocyanins (cyanidin-3-sambubioside (CS), cyanidin-3-glucoside (CG) and cyanidin-3-rutinoside (CR)). Identification and quantitation of CS, CG, and CR in RE was performed by mass spectroscopy and HPLC. RE:triacetyl-β-cyclodextrin (TA-β-CD) inclusion complex (IC) was prepared by a kneading method and characterized by X-ray diffraction (XRD), nuclear magnetic resonance spectroscopy (NMR) and UV-visible spectroscopy. RE or RE:TA-β-CD IC-loaded PLGA or PLA implants were prepared by a solvent extrusion method. In vitro and in vivo controlled release studies were conducted in phosphate-buffered saline Tween-80 (pH 7.4, 37°C) and after subcutaneous administration in male Sprague-Dawley rats, respectively. Anthocyanins were quantified by HPLC at 520 nm. The content of CS, CG, and CR in RE was 0.2, 1.5, and 3.5 wt%, respectively. The chemical stability of anthocyanins in solution was determined to be pH-dependent, and their degradation rate increased with an increase in pH from 2.4 to 7.4. PLGA/PLA millicylindrical implants loaded with 5 or 10 wt% RE exhibited a high initial burst and short release duration of anthocyanins (35–52 and 80–100% CG + CR release after 1 and 14 days, respectively). The cause for rapid anthocyanins release was linked to higher polymer water uptake and porosity associated with the high osmolytic components of large non-anthocyanin fraction of RE. XRD, 1H NMR and UV-visible spectroscopy indicated that the non-anthocyanin fraction molecules of RE formed an IC with TA-β-CD, decreasing the hydrophilicity of RE. Formation of an IC with hydrophobic carrier, TA-β-CD, provided better in vitro/in vivo sustained release of FBR anthocyanins (16–24 and 97–99% CG + CR release, respectively, after 1 and 28 days from 20 wt% RE:TA-β-CD IC/PLA implants) over 1 month, owing to reduced polymer water uptake and porosity. PLA injectable millicylindrical implants loaded with RE:TA-β-CD IC are optimal dosage forms for 1-month slow and continuous delivery of chemopreventive FBR anthocyanins.
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影响因子：
3.7
作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
Schwendeman, Steven P.