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.
The efficiency of drug delivery to the eye using topical drop therapy is limited by the ocular clearance mechanisms. Nanocarriers, able to encapsulate bioactive compounds and slow down their release, may allow for prolonged on-eye residence times when combined with topical application for treatment of ocular conditions. Previously, self-assemblies of methylcellulose (MC) hydrophobized with N-tert-butylacrylamide side chains (MC-g-PNtBAm) were developed. The purpose of the current study was to investigate the impact of the methylcellulose backbone length on the properties of the nanogels. We synthesized MC-g-PNtBAm nanogels using four different molecular weights of MC with two degrees of hydrophobic modification and investigated the physical and chemical properties of the resulting polymeric nanogels. While no significant change could be observed at a high degree of hydrophobization, properties were affected at a lower one. Increasing the molecular weight of MC improved the swelling capacity of the nanogels, increasing their size in water. An effect on the drug release was also noted. Nanogels prepared using MC with a molecular weight of 30 kDa did not retain as much dexamethasone and released it faster compared to those prepared using 230 kDa MC. Thus, besides the degree of hydrophobization, the length of MC chains provides another means of tuning the properties of MC-g-PNtBAm nanogels.
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