Design of Silk-Elastin-Like Protein Nanoparticle Systems with Mucoadhesive Properties

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.

Thermo- and ion-responsive silk-elastin-like proteins and their multiscale mechanisms

“…These results were consistent with the previous study that the LCST could be tuned by adjusting the ratio between hydrophobic and hydrophilic groups, 2 and more hydrophilic derivatives led to higher LCST. 3 Thus, the LCST of Azo-SELP was higher since the sulfonic acid groups in modified tyrosine were hydrophilic. Moreover, the structural transformation in Azo-SELP was suppressed, as inferred by the substantially flatter absorbance curve in the Azo-SELP solution, indicating lower sensitivity of the Azo-SELP response to changes in temperature.…”

“…Soft, adaptive, and responsive biomaterials are extremely useful in engineering: one notable example is silk-elastin-like proteins (SELPs) that exhibit excellent biocompatibility, degradability, and dynamically tunable properties. 1 Engineered SELPs are exceedingly versatile for various processed morphologies, products, and applications that include gels, films, and particles for biosensors and drug delivery, [1][2][3][4] fibres for wound healing, 5,6 and scaffolds for tissue repair. 7,8 SELPs are synthetic materials derived from recombinant DNA technology that create co-polymerized silk-like (GAGAGS) and elastin-like (GXGVP) domains.…”

Recent Advances in Mucoadhesive Interface Materials, Mucoadhesion Characterization, and Technologies

“…Transmucosal drug delivery Charged interactions and thiol bonding [194] Chitosan coated zein Gastrointestinal Resveratrol Oral drug administration Charged interactions [195] based on zwitterionic block copolymers (Figure 10c) have been synthesized by Taipaleenmäki et al [199] using poly(cholesteryl methacrylate) (pCMA) as the hydrophobic block and either poly(2-methacryloyloxyethyl phosphorylcholine) (pMPC) or a random copolymer of MPC and polyethylene glycol methacrylate (PEGMA) as the hydrophilic part. They transformed these polymeric structures into nanoscale micelles and demonstrated their in vitro mucopenetration ability.…”

Recent trends in protein and peptide-based biomaterials for advanced drug delivery

“…More recently, Parker et al developed mucoadhesive SELP nanoparticles for transmucosal drug delivery [ 400 ]. To identify potential mucoadhesive sequences, they generated a series of SELPs with a 1:4 SLP to ELP block ratio with four different guest residues – Cys, Arg, Lys, and Glu.…”