Shear-Thinning Viscous Materials for Subconjunctival Injection of Microparticles
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Research Article Theme: Ocular Drug Delivery and Ophthalmic Formulations Guest Editors: Qingguo Xu and Iok-Hou Pang
Shear-Thinning Viscous Materials for Subconjunctival Injection of Microparticles Shiyu Xia,1,2 Zheng Ding,1,3 Lixia Luo,1,4 Baiwei Chen,1 Joanna Schneider,1,2 Jin Yang,1,4 Charles G. Eberhart,4,5 Walter J. Stark,1,4 and Qingguo Xu1,4,6,7
Received 16 July 2020; accepted 13 November 2020 Abstract. While drug-loaded microparticles (MPs) can serve as drug reservoirs for sustained drug release and therapeutic effects, needle clogging by MPs poses a challenge for ocular drug delivery via injection. Two polymers commonly used in ophthalmic procedures—hyaluronic acid (HA) and methylcellulose (MC)—have been tested for their applicability for ocular injections. HA and MC were physically blended with sunitinib malate (SUN)–loaded PLGA MPs for subconjunctival (SCT) injection into rat eyes. The HA and MC viscous solutions facilitated injection through fine-gauged needles due to their shearthinning properties as shown by rheological characterizations. The diffusion barrier presented by HA and MC reduced burst drug release and extended overall release from MPs. The significant level of MP retention in the conjunctiva tissue post-operation confirmed the minimal leakage of MPs following injection. The safety of HA and MC for ocular applications was demonstrated histologically. KEY WORDS: hyaluronic acid; methylcellulose; shear-thinning materials; microparticles; ocular drug delivery.
INTRODUCTION Subconjunctival (SCT) injection has been used to achieve localized, site-specific delivery of ophthalmic drugs to treat a variety of eye diseases (1–6). Compared to systemic administration where drugs are subject to poor ocular absorption and potential systemic side effects, SCT injection holds the potential to enhance drug availability in the eye while reducing systemic side effects (7,8). Local drug delivery is most commonly Guest Editors: Qingguo Xu and Iok-Hou Pang 1
Center for Nanomedicine, The Johns Hopkins University School of Medicine, 400 North Broadway, Baltimore, Maryland 21231, USA. 2 Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, 3400 North Charles Street, Baltimore, Maryland 21218, USA. 3 Department of Biomedical Engineering, The Johns Hopkins University, 3400 North Charles Street, Baltimore, Maryland 21218, USA. 4 Department of Ophthalmology, The Wilmer Eye Institute, The Johns Hopkins University School of Medicine, 400 North Broadway, Baltimore, Maryland 21231, USA. 5 Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA. 6 Departments of Pharmaceutics and Ophthalmology, Virginia Commonwealth University, Richmond, Virginia 23298, USA. 7 To whom correspondence should be addressed. (e–mail: [email protected])
achieved by the use of topical eye drops, but the rate of drug removal of medicines in eye drops is typically rapid due to blinking, tear film turnover, fast dilution by the lacrimal fluid, and drainage into the nasolacrimal duc
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