The HIV-1 replication inhibitor dapivirine (DPV) is one of the most promising 
drug candidates being used in topical microbicide products for prevention of 
HIV-1 sexual transmission. To be able to block HIV-1 replication, DPV must have 
access to the viral reverse transcriptase enzyme. The window for DPV to access 
the enzyme happens during the HIV-1 cellular infection cycle. Thus, in order for 
DPV to exert its anti-HIV activity, it must be present in the mucosal tissue or 
cells where HIV-1 infection occurs. A dosage form containing DPV must be able to 
deliver the drug to the tissue site of action. Polymeric films are solid dosage 
forms that dissolve and release their payload upon contact with fluids. Films 
have been used as vaginal delivery systems of topical microbicide drug 
candidates including DPV. For use in topical microbicide products containing 
DPV, polymeric films must prove their ability to deliver DPV to the target 
tissue site of action. Ex vivo exposure studies of human ectocervical tissue to 
DPV film revealed that DPV was released from the film and did diffuse into the 
tissue in a concentration dependent manner indicating a process of passive 
diffusion. Analysis of drug distribution in the tissue revealed that DPV 
accumulated mostly at the basal layer of the epithelium infiltrating the upper 
part of the stroma. Furthermore, as a combination microbicide product, 
codelivery of DPV and TFV from a polymeric film resulted in a significant 
increase in DPV tissue concentration [14.21 (single entity film) and 31.03 μg/g 
(combination film)], whereas no impact on TFV tissue concentration was found. In 
vitro release experiments showed that this observation was due to a more rapid 
DPV release from the combination film as compared to the single entity film. In 
conclusion, the findings of this study confirm the ability of polymeric films to 
deliver DPV and TFV to human ectocervical tissue and show that codelivery of the 
two agents has a significant impact on DPV tissue accumulation. These findings 
support the use of polymeric films for topical microbicide products containing 
DPV and/or TFV.