Synthesis and evaluation of mucoadhesive acryloyl-quaternized PDMAEMA nanogels for ocular drug delivery

Abstract

Poly((2-dimethylamino)ethyl methacrylate) (PDMAEMA) nanogels were synthesized via surfactant-free free-radical polymerization technique in aqueous conditions utilizing N,N'-methylene-bis-acrylamide (MBA) as a crosslinking agent. The PDMAEMA nanogels were subsequently quaternized with acryloyl chloride in order to yield mucoadhesive materials which incorporate two mucoadhesive concepts; electrostatic interactions and covalent bond forming acrylate groups. The native PDMAEMA nanogels were found to exhibit good mucoadhesive properties on ex vivo bovine conjunctival tissues, which was found to increase proportionally with the degree of quaternization. With a view to determine the ocular drug delivery capabilities of the materials, both quaternized and native nanogels were loaded with pilocarpine hydrochloride via an absorption method, and their in vitro release profiles were analysed. The nanogels were found to exhibit a high loading capacity (>20% of total weight) and a sustained release over 6h.

Acrylated Eudragit® E PO as a novel polymeric excipient with enhanced mucoadhesive properties for application in nasal drug delivery

“…The intensity of these peaks decreases due to the reduction in the degree of substitution of dimethylamino groups. The appearance of a 5.98-6.44 ppm multiplet in the spectra of AEPO is generally consistent with NMR characterisation of acrylated PDMAEMA previously reported by Brannigan and Khutoryanskiy (2017), who used this method to determine the degree of acryloylation. However, unfortunately, the complex mixture of signals resulting from different repeating units of EPO leads to an overlap of many peaks; this made impossible to use 1 H-NMR spectroscopy for quantitative determination of the degrees of acryloylation.…”

“…Previously, Brannigan and Khutoryanskiy (2017) have demonstrated that poly((2dimethylamino)ethyl methacrylate nanogels modified by reaction with acryloyl chloride exhibited greater retention on ocular mucosa compared to unmodified polymers. Similar modification is also possible for Eudragit ® EPO, Eudragit ® RL and Eudragit ® S100 copolymers containing 25 %, 10 % and 5 % of dimethylamino-groups, respectively (Mustafin, 2011;Moustafine et al, 2011;Moustafine et al, 2013).…”

“…Recently, we have reported the synthesis of mucoadhesive nanogels by polymerisation of 2-dimethylamino)ethyl methacrylate in the presence of N,N'-methylene-bis-acrylamide as a crosslinking agent (Brannigan et al, 2017). The resulting nanogels were subsequently modified by the reaction with acryloyl chloride to introduce acrylated groups capable of forming covalent linkages with thiols present in mucins under physiological conditions.…”

“…The ability of cationic EPO to form interpolyelectrolyte complexes with various anionic polymers was also previously used in the design of solid dosage forms for gastrointestinal delivery (Mustafin, 2011;Mustafin et al, 2011). Since EPO is an approved pharmaceutical excipient and it does contain DMAEMA units in the terpolymer structure, it opens up an interesting opportunity for its simple chemical modification using the chemistry previously described by Brannigan and Khutoryanskiy (2017) with the aim to prepare materials with enhanced mucoadhesive properties.…”

Recent Advancements in Using Polymers for Intestinal Mucoadhesion and Mucopenetration

“…These materials attract a lot of interest not only due to their mucoadhesive properties, but also because they are able to form hydrogels. Here, we will only highlight a few very recent examples in the context of adhesion to intestinal mucosa, although many interesting reports are focusing on applications such as wound dressing,43 ocular drug delivery,44 cargo delivery to different types of cancer,45 or adhesion to the tongue,46 the bladder mucosa,47 the nasal mucosa,48 or the buccal mucosa 49. For instance, the encapsulation of probiotic Lactobacillus acidophilus into alginate and chitosan‐alginate microspheres resulted in not only a slightly better mucoadhesion rate, but also in a 1.7× improved survival rate of the encapsulated probiotic compared to the free Lactobacillus acidophilus after 2 h exposure to simulated gastric fluid 50.…”