The Vaginal-PVPA: A Vaginal Mucosa-Mimicking In Vitro Permeation Tool for Evaluation of Mucoadhesive Formulations.

Martina Pattacini,Fabio Sonvico,Natasa Škalko-Basnet,Richard Wibel,Margherita Falavigna,Gøril Eide Flaten

doi:10.3390/pharmaceutics12060568

Martina Pattacini, Fabio Sonvico + Show 4 more

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https://doi.org/10.3390/pharmaceutics12060568

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Abstract

Drug administration to the vaginal site has gained increasing attention in past decades, highlighting the need for reliable in vitro methods to assess the performance of novel formulations. To optimize formulations destined for the vaginal site, it is important to evaluate the drug retention within the vagina as well as its permeation across the mucosa, particularly in the presence of vaginal fluids. Herewith, the vaginal-PVPA (Phospholipid Vesicle-based Permeation Assay) in vitro permeability model was validated as a tool to evaluate the permeation of the anti-inflammatory drug ibuprofen from liposomal formulations (i.e., plain and chitosan-coated liposomes). Drug permeation was assessed in the presence and absence of mucus and simulated vaginal fluid (SVF) at pH conditions mimicking both the healthy vaginal premenopausal conditions and vaginal infection/pre-puberty/post-menopause state. The permeation of ibuprofen proved to depend on the type of formulation (i.e., chitosan-coated liposomes exhibited lower drug permeation), the mucoadhesive formulation properties and pH condition. This study highlights both the importance of mucus and SVF in the vaginal model to better understand and predict the in vivo performance of formulations destined for vaginal administration, and the suitability of the vaginal-PVPA model for such investigations.

Highlights

The administration of drugs to the vaginal site has proven advantageous for both local and systemic therapy thanks to the possibility of self-administration, the potential of prolonged treatment due to long residence time of the drug in loco, and the avoidance of first-pass metabolism in the case of systemic therapies [1]
To address the challenges of vaginal drug delivery, we evaluated drug permeation at two pH conditions: the healthy vaginal conditions of pre-menopausal women and the conditions caused by vaginal infections as well as conditions present in pre-puberty or post-menopause women
To investigate the model’s ability to handle relevant vaginal formulations, liposomal formulations able to be retained at the vaginal site and able to release the incorporated drug to the mucosal tissue were used as simple model formulations

Summary

Introduction

The administration of drugs to the vaginal site has proven advantageous for both local and systemic therapy thanks to the possibility of self-administration, the potential of prolonged treatment due to long residence time of the drug in loco, and the avoidance of first-pass metabolism in the case of systemic therapies [1]. The mixture of fluids that end up in the vagina (i.e., cervical mucus, semen, etc.) and those that originate from the vagina can greatly impact the retention of the formulation and the subsequent drug release [4]. This mixture of fluids is, the first physical barrier that the administered formulations encounter, and it has been demonstrated that its composition, osmolarity, and pH can significantly affect the delivery of drugs [5]. Chitosan-based products have gained increasing momentum due to their biodegradability, biocompatibility, mucoadhesion, and intrinsic antimicrobial effects [6]

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