Abstract
Transmucosal drug delivery is a promising avenue to improve therapeutic efficacy through localized therapeutic administration. Drug delivery systems that increase retention in the mucosal layer are needed to improve efficiency of such transmucosal platforms. However, the applicability of such systems is often limited by the range of chemistries and properties that can be achieved. Here we present the design and implementation of silk-elastin-like proteins (SELPs) with mucoadhesive properties. SELP-based micellar-like nanoparticles provide a system to tailor chemical and physical properties through genetic engineering of the SELP sequence, which enables the fabrication of nanoparticles with specific chemical and physical features. Analysis of the adhesion of four different SELP-based nanoparticle systems in an artificial mucus system, as well as in in vitro cellular assays indicates that addition of mucoadhesive chemical features on the SELP systems increases retention of the particles in mucosal environments. The results indicated that SELP-based nanoparticles provide a useful approach to study and develop transmucosal protein drug delivery system with unique mucoadhesive properties. Future studies will serve to further expand the range of achievable properties, as well as the utilization of SELPs to fabricate mucoadhesive materials for in vivo testing.
Highlights
Mucus membranes that line the surfaces of many organs establish a protective barrier to microbial infection and unwanted foreign objects in the body through trapping and efficient removal
Transmucosal drug delivery systems are an important route for administration of a variety of drug classes
The design flexibility afforded by genetic engineering technology allows for the formation of multifunctional, dynamic silk-elastin-like proteins (SELPs) nanoparticles
Summary
Mucus membranes that line the surfaces of many organs establish a protective barrier to microbial infection and unwanted foreign objects in the body through trapping and efficient removal. Consisting of up to 95% water, mucus layers are composed of hydrophilic glycoproteins known as mucins. Mucins comprise 3–5% of the mucus composition and are key to the barrier properties of mucus, providing structural integrity through physical entanglements and crosslinks [1]. Lipids, carbohydrates, microbes, and enzymes are present in the mucus. Mucus barriers are essential to human health, their dynamic properties present a major challenge to drug delivery. Mucus turnover rates (i.e., time from initial mucus production to the time of complete replacement) range from minutes (e.g., in ocular mucosa [2]) to 1–2 days (e.g., in gastric and intestinal mucosa [3]), which leads to the rapid clearance of transmucosal and orally administered drugs
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