In vitro and ex vivo evaluations on transdermal delivery of the HIV inhibitor IQP-0410.
In vitro and ex vivo evaluations on transdermal delivery of the HIV inhibitor IQP-0410.
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DOI：
10.1371/journal.pone.0075306
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Buckheit RW Jr
中科院分区：
文献类型：
--
作者：
Ham AS;Lustig W;Yang L;Boczar A;Buckheit KW;Buckheit RW Jr
本研究的目的是研究配制成透皮膜的嘧啶二酮IQP-0410的理化和体外/离体特性。IQP-0410是一种有效的治疗性抗HIV非核苷类逆转录酶抑制剂，通过常规口服给药，将经历广泛的首过代谢。因此，通过溶剂浇铸将IQP-0410配制成基于乙基纤维素/HPMC的透皮膜。进行了徒手评价，以评价大体物理特征。在Franz池和USP-4溶出容器中进行体外释放研究。在人表皮组织模型上进行离体释放和渗透性测定，并收集渗透的IQP-0410用于CEM-SS细胞和PBMC中的体外HIV-1效力测定。膜制剂D3产生柔韧、坚固的透皮膜，其负载有2%（w/w）IQP-0410。由60%（w/w）乙基纤维素和20%（w/w）HPMC组成，膜含有< 1.2%（w/w）的水并且是吸湿性的，导致在潮湿条件下显著溶胀。膜的透水性导致在26小时内完全体外溶解和药物释放。当应用于离体表皮组织时，膜对组织无毒，并且对体外功效测定中使用的HIV靶细胞也无毒。在3天的应用中，薄膜以0.94 ± 0.06 µg/cm 2/hr的零级速率通过皮肤组织递送IQP-0410，在基础培养基中收集了134 ± 14.7 µM。递送的IQP-0410导致抗HIV-1的体外EC 50值为2.56 ± 0.40 nM（CEM-SS）和0.58 ± 0.03 nM（PBMC）。当在标准和加速环境条件下包装在铝箔袋中时，薄膜制剂显示与目标值无显著偏离。得出的结论是，透皮薄膜制剂是一种潜在可行的IQP-0410给药方法，值得进一步开发。
The aim of this study was to investigate the physicochemical and in vitro/ex vivo characteristics of the pyrmidinedione IQP-0410 formulated into transdermal films. IQP-0410 is a potent therapeutic anti-HIV nonnucleoside reverse transcriptase inhibitor that would be subjected to extensive first pass metabolism, through conventional oral administration. Therefore, IQP-0410 was formulated into ethyl cellulose/HPMC-based transdermal films via solvent casting. In mano evaluations were performed to evaluate gross physical characteristics. In vitro release studies were performed in both Franz cells and USP-4 dissolution vessels. Ex vivo release and permeability assays were performed on human epidermal tissue models, and the permeated IQP-0410 was collected for in vitro HIV-1 efficacy assays in CEM-SS cells and PBMCs. Film formulation D3 resulted in pliable, strong transdermal films that were loaded with 2% (w/w) IQP-0410. Composed of 60% (w/w) ethyl cellulose and 20% (w/w) HPMC, the films contained < 1.2% (w/w) of water and were hygroscopic resulting in significant swelling under humid conditions. The water permeable nature of the film resulted in complete in vitro dissolution and drug release in 26 hours. When applied to ex vivo epidermal tissues, the films were non-toxic to the tissue and also were non-toxic to HIV target cells used in the in vitro efficacy assays. Over a 3 day application, the films delivered IQP-0410 through the skin tissue at a zero-order rate of 0.94 ± 0.06 µg/cm2/hr with 134 ± 14.7 µM collected in the basal media. The delivered IQP-0410 resulted in in vitro EC50 values against HIV-1 of 2.56 ± 0.40 nM (CEM-SS) and 0.58 ± 0.03 nM (PBMC). The film formulation demonstrated no significant deviation from target values when packaged in foil pouches under standard and accelerated environmental conditions. It was concluded that the transdermal film formulation was a potentially viable method of administering IQP-0410 that warrants further development.
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影响因子：
10.8
作者：
Li, YP;Pei, YY;Gao, XJ
通讯作者：
Gao, XJ
影响因子：
4.9
作者：
Buckheit, Karen Watson;Yang, Lu;Buckheit, Robert W., Jr.
通讯作者：
Buckheit, Robert W., Jr.
影响因子：
56.9
作者：
POPOVIC, M;SARNGADHARAN, MG;GALLO, RC
通讯作者：
GALLO, RC
影响因子：
4.2
作者：
Paudel KS;Milewski M;Swadley CL;Brogden NK;Ghosh P;Stinchcomb AL
通讯作者：
Stinchcomb AL
影响因子：
3.2
作者：
CANNON, CL;NEAL, PJ;KLAUSNER, M
通讯作者：
KLAUSNER, M