Nanogels of Methylcellulose Hydrophobized with N-tert-butylacrylamide for Ocular Drug Delivery

Overview

Journal Drug Deliv Transl Res

Publisher Springer

Specialty Pharmacology

Date 2016 Nov 6

PMID 27807769

Citations 15

Authors

Marion Jamard

Todd Hoare

Heather Sheardown

Affiliations

Soon will be listed here.

Abstract

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.

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References

Gupta D, Tator C, Shoichet M . Fast-gelling injectable blend of hyaluronan and methylcellulose for intrathecal, localized delivery to the injured spinal cord. Biomaterials. 2005; 27(11):2370-9. DOI: 10.1016/j.biomaterials.2005.11.015. View

Musial W, Voncina B, Pluta J, Kokol V . The study of release of chlorhexidine from preparations with modified thermosensitive poly-N-isopropylacrylamide microspheres. ScientificWorldJournal. 2012; 2012:243707. PMC: 3353284. DOI: 10.1100/2012/243707. View

Lemarchand C, Gref R, Couvreur P . Polysaccharide-decorated nanoparticles. Eur J Pharm Biopharm. 2004; 58(2):327-41. DOI: 10.1016/j.ejpb.2004.02.016. View

Abd El-Rehim H, Swilem A, Klingner A, Hegazy E, Hamed A . Developing the potential ophthalmic applications of pilocarpine entrapped into polyvinylpyrrolidone-poly(acrylic acid) nanogel dispersions prepared by γ radiation. Biomacromolecules. 2013; 14(3):688-98. DOI: 10.1021/bm301742m. View

Nagarwal R, Singh P, Kant S, Maiti P, Pandit J . Chitosan nanoparticles of 5-fluorouracil for ophthalmic delivery: characterization, in-vitro and in-vivo study. Chem Pharm Bull (Tokyo). 2011; 59(2):272-8. DOI: 10.1248/cpb.59.272. View

Gupta K, Khandekar K . Temperature-responsive cellulose by ceric(IV) ion-initiated graft copolymerization of N-isopropylacrylamide. Biomacromolecules. 2003; 4(3):758-65. DOI: 10.1021/bm020135s. View

Griffith M, Osborne R, Munger R, Xiong X, Doillon C, Laycock N . Functional human corneal equivalents constructed from cell lines. Science. 1999; 286(5447):2169-72. DOI: 10.1126/science.286.5447.2169. View

Gaudana R, Jwala J, Boddu S, Mitra A . Recent perspectives in ocular drug delivery. Pharm Res. 2008; 26(5):1197-216. PMC: 4516219. DOI: 10.1007/s11095-008-9694-0. View

Ganguly K, Chaturvedi K, More U, Nadagouda M, Aminabhavi T . Polysaccharide-based micro/nanohydrogels for delivering macromolecular therapeutics. J Control Release. 2014; 193:162-73. DOI: 10.1016/j.jconrel.2014.05.014. View

10.

Moya-Ortega M, Alvarez-Lorenzo C, Concheiro A, Loftsson T . Cyclodextrin-based nanogels for pharmaceutical and biomedical applications. Int J Pharm. 2012; 428(1-2):152-63. DOI: 10.1016/j.ijpharm.2012.02.038. View

11.

Guo Q, Wu Z, Zhang X, Sun L, Li C . Phenylboronate-diol crosslinked glycopolymeric nanocarriers for insulin delivery at physiological pH. Soft Matter. 2014; 10(6):911-20. DOI: 10.1039/c3sm52485j. View

12.

Moran M, Carroll W, Selezneva I, Gorelov A, Rochev Y . Cell growth and detachment from protein-coated PNIPAAm-based copolymers. J Biomed Mater Res A. 2007; 81(4):870-6. DOI: 10.1002/jbm.a.31089. View

13.

Yoncheva K, Vandervoort J, Ludwig A . Development of mucoadhesive poly(lactide-co-glycolide) nanoparticles for ocular application. Pharm Dev Technol. 2009; 16(1):29-35. DOI: 10.3109/10837450903479954. View

14.

Jansook P, Stefansson E, Thorsteinsdottir M, Sigurdsson B, Kristjansdottir S, Bas J . Cyclodextrin solubilization of carbonic anhydrase inhibitor drugs: formulation of dorzolamide eye drop microparticle suspension. Eur J Pharm Biopharm. 2010; 76(2):208-14. DOI: 10.1016/j.ejpb.2010.07.005. View

15.

Liu R, Sun L, Fang S, Wang S, Chen J, Xiao X . Thermosensitive in situ nanogel as ophthalmic delivery system of curcumin: development, characterization, in vitro permeation and in vivo pharmacokinetic studies. Pharm Dev Technol. 2015; 21(5):576-82. DOI: 10.3109/10837450.2015.1026607. View

16.

Gupta H, Aqil M, Khar R, Ali A, Bhatnagar A, Mittal G . Biodegradable levofloxacin nanoparticles for sustained ocular drug delivery. J Drug Target. 2010; 19(6):409-17. DOI: 10.3109/1061186X.2010.504268. View

17.

Qaddoumi M, Ueda H, Yang J, Davda J, Labhasetwar V, Lee V . The characteristics and mechanisms of uptake of PLGA nanoparticles in rabbit conjunctival epithelial cell layers. Pharm Res. 2004; 21(4):641-8. DOI: 10.1023/b:pham.0000022411.47059.76. View

18.

Patton T, Robinson J . Quantitative precorneal disposition of topically applied pilocarpine nitrate in rabbit eyes. J Pharm Sci. 1976; 65(9):1295-301. DOI: 10.1002/jps.2600650909. View

19.

Hoffman A, Stayton P, Bulmus V, Chen G, Chen J, Cheung C . Founder's Award, Society for Biomaterials. Sixth World Biomaterials Congress 2000, Kamuela, HI,May 15-20, 2000. Really smart bioconjugates of smart polymers and receptor proteins. J Biomed Mater Res. 2000; 52(4):577-86. DOI: 10.1002/1097-4636(20001215)52:4<577::aid-jbm1>3.0.co;2-5. View

20.

Loftsson T, Hreinsdottir D, Stefansson E . Cyclodextrin microparticles for drug delivery to the posterior segment of the eye: aqueous dexamethasone eye drops. J Pharm Pharmacol. 2007; 59(5):629-35. DOI: 10.1211/jpp.59.5.0002. View