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.
School of Biomedical Engineering, McMaster University, 1280 Main Street West, Hamilton, Ontario, L8S 4L8, Canada.
Marion
M
Jamard
Department of Chemical Engineering, McMaster University, 1280 Main Street West, Hamilton, L8S 4L8, Canada.
Todd
T
Hoare
Department of Chemical Engineering, McMaster University, 1280 Main Street West, Hamilton, L8S 4L8, Canada. sheardow@mcmaster.ca.
Heather
H
Sheardown
D000178:Acrylamides / Q000008:administration & dosage* / Q000737:chemistry; D060433:Administration, Ophthalmic; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003907:Dexamethasone / Q000008:administration & dosage / Q000737:chemistry; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry; D065546:Drug Liberation; D004847:Epithelial Cells / Q000187:drug effects; D005782:Gels; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008747:Methylcellulose / Q000008:administration & dosage* / Q000737:chemistry; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry
D000178:Acrylamides; D004337:Drug Carriers; D005782:Gels; D003907:Dexamethasone; D008747:Methylcellulose; C115287:tert-butylacrylamide
Drug delivery/release; Hydrophobization; Methylcellulose; Nanogels; Ophthalmic; Polysaccharide