Hydrogen‐Bonded Complexes and Blends of Poly(acrylic acid) and Methylcellulose: Nanoparticles and Mucoadhesive Films for Ocular Delivery of Riboflavin

Abstract

Poly(acrylic acid) (PAA) and methylcellulose (MC) are able to form hydrogen-bonded interpolymer complexes (IPCs) in aqueous solutions. In this study, the complexation between PAA and MC is explored in dilute aqueous solutions under acidic conditions. The formation of stable nanoparticles is established, whose size and colloidal stability are greatly dependent on solution pH and polymers ratio in the mixture. Poly(acrylic acid) and methylcellulose are also used to prepare polymeric films by casting from aqueous solutions. It is established that uniform films can be prepared by casting from polymer mixture solutions at pH 3.4-4.5. At lower pHs (pH < 3.0) the films have inhomogeneous morphology resulting from strong interpolymer complexation and precipitation of polycomplexes, whereas at higher pHs (pH 8.3) the polymers form fully immiscible blends because of the lack of interpolymer hydrogen-bonding. The PAA/MC films cast at pH 4 are shown to be non-irritant to mucosal surfaces. These films provide a platform for ocular formulation of riboflavin, a drug used for corneal crosslinking in the treatment of keratoconus. An in vitro release of riboflavin as well as an in vivo retention of the films on corneal surfaces can be controlled by adjusting PAA/MC ratio in the formulations.

Polysaccharides in Ocular Drug Delivery

“…Film forming properties and biocompatibility of cellulose ethers makes them a good excipient for modifying ocular insert properties. The addition of methylcellulose to polyacrylic acid films provided prolonged riboflavin release due to the formation of a hydrogen bond network and a decrease in irritation effects [98]. Abilova et al [99] prepared films based on chitosan and its blends with poly(2-ethyl-2-oxazoline).…”

In situ gelling systems based on Pluronic F127/Pluronic F68 formulations for ocular drug delivery

“…Limax flavus slugs were chosen because they exhibited a greater response (more mucus secretion) to irritants compared to some other species, in addition to their local availability (Khutoryanskaya et al, 2008). We have previously validated the slug mucosal irritation assay against ocular administration of formulations in rabbits (Khutoryanskaya, 2014). Figure 4 illustrates the effect of various Pluronic formulations on the mucus production in Limax flavus.…”

Novel in situ gelling ocular films for the opioid growth factor-receptor antagonist-naltrexone hydrochloride: Fabrication, mechanical properties, mucoadhesion, tolerability and stability studies

“…In reality, there are no guidelines or 521 regulatory working ranges for acceptable mechanical properties of 522 ocular films. In this study, film number 10 was selected, been employed as a tool to study the phase separation 527 and homogeneity of polymeric films composed of more than one 528 polymeric material(Khutoryanskaya et al, 2014;Luo et al, 2008).529 Fig. 3 shows the surface morphology of F1-F3, fabricated from 530 different polymers MC, CMC and ALG, respectively; and F7-531 F9 containing different plasticisers GLY, TEC and PEG 400, 532 respectively.…”