Nanogels of methylcellulose hydrophobized with N-tert-butylacrylamide for ocular drug delivery
While eye drops account for the majority of ophthalmic formulation for drug delivery, their efficiency is limited by rapid pre-corneal loss. In this study, we investigate nanogel suspensions in order to improve the topical ocular therapy by reducing dosage and frequency of administration. We synthesized self-assembling nanogels of 140 nm by grafting side chains of poly(N-tert-butylacrylamide) (PNtBAm) on methylcellulose via cerium ammonium nitrate. Successful grafting of PNtBAm onto methylcellulose (MC) was confirmed by both NMR and ATR. Synthesized molecules (MC-g-PNtBAm) self-assembled in water driven by hydrophobic interaction of the grafted side chains creating colloid solutions. Materials were synthesized by changing feed ratios of acid, initiator and monomer in order to control the degree of hydrophobic modification. The nanogels were tested for different degrees of grafting. Viability studies performed with HCE cells testified to the biocompatibility of poly(N-tert-butylacrylamide) grafted methylcellulose nanogels. Dexamethasone was entrapped with an efficiency superior to 95 % and its release presented minimal burst phase. Diffusion of drug from the nanogels was found to be delayed by increasing the degree of grafting. The release profile of the entrapped compound from the MC-g-PNtBAm nanogels can thus be tuned by simply adjusting the degree of hydrophobic modification. MC-g-PNtBAm nanogels present promising properties for ocular drug delivery.
KeywordsMethylcellulose Polysaccharide Hydrophobization Nanogels Ophthalmic Drug delivery/release
Compliance with ethical standards
The funding support of the Natural Sciences and Engineering Research Council of Canada is gratefully acknowledged.
The authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge, or beliefs) in the subject matter or materials discussed in this manuscript.
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