Mucoadhesion of Progesterone-Loaded Drug Delivery Nanofiber Constructs.

Francis Brako,Duncan Q. M. Craig,Richard Thorogate,Mohan Edirisinghe,Bahijja Raimi-Abraham,Suntharavathanan Mahalingam

doi:10.1021/acsami.8b03329

Abstract

Mucoadhesive delivery systems have attracted remarkable interest recently, especially for their potential to prolong dosage form resident times at sites of application such as the vagina or nasal cavity, thereby improving convenience and compliance as a result of less frequent dosage. Mucoadhesive capabilities need to be routinely quantified during the development of these systems. This is however logistically challenging due to difficulties in obtaining and preparing viable mucosa tissues for experiments. Utilizing artificial membranes as a suitable alternative for quicker and easier analyses of mucoadhesion of these systems is currently being explored. In this study, the mucoadhesive interactions between progesterone-loaded fibers (with varying carboxymethyl cellulose (CMC) content) and either artificial (cellulose acetate) or mucosa membranes are investigated by texture analysis and results across models are compared. Mucoadhesion to artificial membrane was about 10 times that of mucosa, though statistically significant ( p = 0.027) association between the 2 data sets was observed. Furthermore, a hypothesis relating fiber-mucosa interfacial roughness (and unfilled void spaces on mucosa) to mucoadhesion, deduced from some classical mucoadhesion theories, was tested to determine its validity. Points of interaction between the fiber and mucosa membrane were examined using atomic force microscopy (AFM) to determine the depths of interpenetration and unfilled voids/roughness, features crucial to mucoadhesion according to the diffusion and mechanical theories of mucoadhesion. A Kendall's tau and Goodman-Kruskal's gamma tests established a monotonic relationship between detaching forces and roughness, significant with p-values of 0.014 and 0.027, respectively. A similar relationship between CMC concentration and interfacial roughness was also confirmed. We conclude that AFM analysis of surface geometry following mucoadhesion can be explored for quantifying mucoadhesion as data from interfacial images correlates significantly with corresponding detaching forces, a well-established function of mucoadhesion.

Highlights

Mucoadhesion is defined as an interactive state in which two material surfaces, at least one being biological in nature and typically a mucosa membrane, are held together by interfacial forces for a prolonged period of time.[1]
These progesterone-loaded fibrous materials (Figure 1b) are the starting material for the development of vaginal inserts, which will be used to deliver suitable amounts of progesterone for the prevention of premature labor in women considered at high risk
As a continuation of our previous work on investigating the release of progesterone from these fiber systems, a range of assessments of mucoadhesion from different perspectives were developed for the purpose of a comprehensive characterization of mucoadhesive prospects of these fibers and reported

Summary

INTRODUCTION

Mucoadhesion is defined as an interactive state in which two material surfaces, at least one being biological in nature and typically a mucosa membrane, are held together by interfacial forces for a prolonged period of time.[1]. It was hypothesized that a nanoscale analyses of these surfaces by a suitable method like AFM could offer trends useful for quantifying mucoadhesion Testing this hypothesis is the basis for this study. As the study sought to investigate the strength of associations between data sets from either different mucoadhesion models or methods of quantification, Kendall’s tau and/or Goodman−Kruskal’s gamma analyses were used in testing the hypotheses being determined This fiber mucoadhesion investigations are crucial part of a project seeking to develop novel fiber-based vaginal dosage forms, where mucoadhesive fibers from various polymer blends have been developed[20] and suitable candidates selected and loaded with progesterone, performing as functional drug delivery systems.[26]

EXPERIMENTAL DETAILS

RESULTS AND DISCUSSION

CONCLUSIONS

■ ACKNOWLEDGMENTS

■ REFERENCES