Optimization of naltrexone diclofenac codrugs for sustained drug delivery across microneedle-treated skin.
Optimization of naltrexone diclofenac codrugs for sustained drug delivery across microneedle-treated skin.
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DOI：
10.1007/s11095-013-1147-8
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发表时间：
2014-01
影响因子：
3.7
通讯作者：
Stinchcomb, Audra L.
中科院分区：
文献类型：
--
作者：
Ghosh, Priyanka;Lee, DoMin;Kim, Kyung Bo;Stinchcomb, Audra L.
这项工作的目的是优化用于在微针处理的皮肤上延长递送的共药物的结构。将模型化合物纳洛酮与非特异性环氧合酶抑制剂双氯芬酸连接，以增加微针治疗后的孔寿命，并开发纳洛酮的7天透皮系统。在稳定性和溶解度方面比较了纳洛酮和双氯芬酸的四种不同的联合药物。定量分析了母体药物和联合药物的透皮通量、渗透性和皮肤浓度，建立了结构-渗透性关系。结果表明，所有的联合药物在皮肤中生物转化。转化程度取决于结构，与仲醇连接的结构相比，苯酚连接的共药物不太稳定。对于苯酚连接的联合药物，纳洛酮穿过微针处理的皮肤的通量和双氯芬酸的皮肤浓度较高。聚乙二醇连接增强了共药物的溶解度，这转化为通量增强。目前的研究表明，通过结构设计优化可以提高复方制剂的稳定性和纳洛酮的通量。在稳定性和药物递送方面，聚乙二醇连接的纳洛酮双氯芬酸联合药物更适合7天药物递送系统。
The purpose of this work was to optimize the structure of codrugs for extended delivery across microneedle treated skin. Naltrexone, the model compound was linked with diclofenac, a nonspecific cyclooxygenase inhibitor to enhance the pore lifetime following microneedle treatment and develop a 7 day transdermal system for naltrexone. Four different codrugs of naltrexone and diclofenac were compared in terms of stability and solubility. Transdermal flux, permeability and skin concentration of both parent drugs and codrugs were quantified to form a structure permeability relationship. The results indicated that all codrugs bioconverted in the skin. The degree of conversion was dependent on the structure, phenol linked codrugs were less stable compared to the secondary alcohol linked structures. The flux of naltrexone across microneedle treated skin and the skin concentration of diclofenac were higher for the phenol linked codrugs. The polyethylene glycol link enhanced solubility of the codrugs, which translated into flux enhancement. The current studies indicated that formulation stability of codrugs and the flux of naltrexone can be enhanced via structure design optimization. The polyethylene glycol linked naltrexone diclofenac codrug is better suited for a 7 day drug delivery system both in terms of stability and drug delivery.
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影响因子：
3.7
作者：
POTTS, RO;GUY, RH
通讯作者：
GUY, RH
影响因子：
3.7
作者：
Kalluri, Haripriya;Banga, Ajay K.
通讯作者：
Banga, Ajay K.
影响因子：
3.8
作者：
Vaddi, Haranath K.;Banks, Stan L.;Stinchcomb, Audra L.
通讯作者：
Stinchcomb, Audra L.
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：
3.8
作者：
DITTERT, LW;HIGUCHI, T
通讯作者：
HIGUCHI, T