Department of Chemistry, Oak Crest Institute of Science, Pasadena, California 91107, USA.
J Pharm Sci. 2012 Aug;101(8):2833-43. doi: 10.1002/jps.23208. Epub 2012 May 22.
Intravaginal delivery of microbicide combinations is a promising approach for the prevention of sexually transmitted infections, but requires a method of providing simultaneous, independent release of multiple agents into the vaginal compartment. A novel intravaginal ring (IVR) platform has been developed for simultaneous delivery of the reverse-transcriptase inhibitor tenofovir (TFV) and the guanosine analogue antiviral acyclovir (ACV) with independent control of release rate for each drug. The IVR is based on a pod design, with up to 10 individual polymer-coated drug cores embedded in the ring releasing through preformed delivery channels. The release rate from each pod is controlled independently of the others by the drug properties, polymer coating, and size and number of delivery channels. Pseudo-zero-order in vitro release of TFV (144 ± 10 µg day) and ACV (120 ± 19 µg day⁻¹) from an IVR containing both drugs was sustained for 28 days. The mechanical properties of the pod IVR were evaluated and compared with the commercially available Estring® (Pfizer, NY, NY). The pod-IVR design enables the vaginal delivery of multiple microbicides with differing physicochemical properties, and is an attractive approach for the sustained intravaginal delivery of relatively hydrophilic drugs that are difficult to deliver using conventional matrix IVR technology.
阴道内递药系统是预防性传播感染的一种很有前景的方法,但需要有一种方法能同时将多种药物独立递送到阴道腔室中。现已开发出一种新型阴道内环(IVR)平台,用于同时递药,将逆转录酶抑制剂替诺福韦(TFV)和鸟嘌呤类似物抗病毒药阿昔洛韦(ACV)递送至阴道腔室,且能独立控制两种药物的释放速率。IVR 基于荚膜设计,每个环内可嵌入多达 10 个单独的聚合物包被药物核心,通过预先形成的释放通道释放药物。荚膜 IVR 中的每个荚膜的释放速率可通过药物特性、聚合物包衣、释放通道的大小和数量独立控制,与其他荚膜互不影响。载有两种药物的 IVR 体外呈现出近似零级的释放行为,TFV(144 ± 10 µg day)和 ACV(120 ± 19 µg day⁻¹)可持续释放 28 天。荚膜 IVR 的机械性能得到了评估,并与市售的 Estring®(辉瑞公司,纽约州,纽约)进行了比较。荚膜 IVR 设计使阴道内递药能够递送至多种具有不同理化性质的杀微生物剂,且是一种有吸引力的方法,可用于递送至阴道腔室中相对亲水的药物,而这些药物使用常规基质 IVR 技术递药非常困难。