Competing properties of mucoadhesive films designed for localized delivery of imiquimod

Abstract

Oral mucosal delivery has gained prominence in the last two decades because the rich vasculature of the tissue enables rapid delivery and avoidance of first pass metabolism. Although commercial mucoadhesives are used for systemic delivery, systems are not currently available for treatment of local conditions. In the present work, mucoadhesive films are being developed for locally controlled release of an immune response modifier for preventing precancerous lesions from progressing to oral squamous cell carcinoma. Previous research showed that films composed of polyvinylpyrrolidone (PVP) and carboxymethylcellulose (CMC) released imiquimod in a sustained manner for 3 hr. In continuing development of the system, additional key properties were investigated with changes in composition. While adhesive properties in pull-off (0.42±0.03 to 1.1±0.1 N/cm2) and shear adhesion (1.7±0.25 to 5.6±1.4 N/cm2) increased with increasing PVP content of films, tensile properties, such as modulus (6.9±1.5 to 1.8±0.2 MPa) and ultimate strength (4.2±0.7 to 2.1±0.02 MPa), decreased as PVP content increased. Release profiles of the films showed that an increased PVP content resulted in burst release and faster erosion compared to sustained release and slower erosion with more CMC. Studies of transport kinetics showed that the films doubled the amount of imiquimod localized within epithelium compared to drug in solution, increasing their potential for local treatment of oral dysplasia. The mucoadhesive drug delivery system based on CMC and PVP offers a wide range of these properties without addition of new constituents.

Positive/negative surface charge of chitosan based nanogels and its potential influence on oral insulin delivery

“…The clinical effects were compromised by pain and allergy frequently 44 M a n u s c r i p t occurred in the local injection following lipoatrophy, which result in atrophy of fats in 45 the skin layers (Babiker & Datta, 2011;Borus & Laffel, 2010;Cefalu, 2004). Oral 46 delivery is considered as a favorable and alternative route for insulin administration 47 because oral administration can serve as long-term hypoglycemic effect and simulate 48 the physiological hypoglycemic mechanism by directly delivering insulin into liver 49 after absorption (Ramineni, Cunningham, Dziubla, & Puleo, 2013). However, 50…”

Effects of epidermal growth factor-loaded mucoadhesive films on wounded oral tissue rafts

“…(17) Briefly, solutions of PVP (40% w/v aqueous solution of PVP combined with ethanol at 1:1 v/v and followed by addition of 50% v/v propylene glycol) and CMC (2% w/v aqueous solution) were mixed. Human recombinant EGF (Shenandoah Biotechnology, Warwick, PA) or lysozyme (Sigma) solubilized in deionized water containing 0.1 % bovine serum albumin (BSA; Sigma) was then added to the polymer solution, thoroughly mixed using a heavy duty rotator at high speed (RotoTorque; Cole Parmer, Chicago, IL), and left overnight at 43°C to remove bubbles.…”

Polymeric drug delivery systems for intraoral site‐specific chemoprevention of oral cancer

“…A variety of polymeric local drug delivery systems (Figure ) have been developed and evaluated for their potential against OSCC . The delivery of chemopreventive agents directly into the affected site of the mouth provides multiple therapeutic advantages .…”

“…Importantly, intraoral site‐specific drug delivery has been shown to prevent the progression of recognized premalignant lesions of oral epithelial dysplasia to overt OSCC and to inhibit local tumor recurrence and the development of new, second primary tumors . Intraoral therapy has emerged as a strong alternative to systemic chemotherapy for effective and improved oral cancer chemoprevention without any significant side effects/toxicity . Most local delivery systems are self‐administrable and can be removed from the site when needed, thereby providing greater convenience and patient compliance.…”