Injectable drug depot engineered to release multiple ophthalmic therapeutic agents with precise time profiles for postoperative treatment following ocular surgery

被引：30

作者：

Mohammadi, Maziar ^{[1
,2
,3
,4
]}

Patel, Kisha ^{[2
,3
]}

Alaie, Seyedeh P. ^{[2
,3
,5
]}

Shmueli, Ron B. ^{[2
,3
]}

Besirli, Cagri G. ^{[6
]}

Larson, Ronald G. ^{[1
,4
,7
]}

Green, Jordan J. ^{[2
,3
,8
,9
,10
,11
,12
]}

机构：

[1] Univ Michigan, Dept Mech Engn, Ann Arbor, MI 48109 USA

[2] Johns Hopkins Univ, Sch Med, Dept Biomed Engn, Baltimore, MD 21205 USA

[3] Johns Hopkins Univ, Sch Med, Translat Tissue Engn Ctr, Baltimore, MD 21205 USA

[4] Univ Michigan, Biointerface Inst, Ann Arbor, MI 48109 USA

[5] Howard Univ, Coll Med, Washington, DC 20001 USA

[6] Univ Michigan, Kellogg Eye Ctr, Dept Ophthalmol & Visual Sci, Ann Arbor, MI 48105 USA

[7] Univ Michigan, Dept Chem Engn, Ann Arbor, MI 48109 USA

[8] Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Baltimore, MD 21231 USA

[9] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21231 USA

[10] Johns Hopkins Univ, Sch Med, Dept Neurosurg, Baltimore, MD 21231 USA

[11] Johns Hopkins Univ, Sch Med, Dept Chem & Biomol Engn, Baltimore, MD 21231 USA

[12] Johns Hopkins Univ, Sch Med, Dept Mat Sci & Engn, Baltimore, MD 21231 USA

来源：

ACTA BIOMATERIALIA | 2018年 / 73卷

基金：

美国国家卫生研究院; 美国国家科学基金会;

关键词：

Injectable; Hydrogel; Microparticle; Controlled release; Ophthalmology; Postoperative; FLUOCINOLONE ACETONIDE IMPLANT; GLAUCOMA MEDICATION ADHERENCE; LONG-TERM-BENEFIT; RISK-FACTORS; INTRAOCULAR-PRESSURE; CATARACT-SURGERY; INTRAVITREAL DELIVERY; POSTERIOR SEGMENT; CONTACT-LENSES; MACULAR EDEMA;

D O I：

10.1016/j.actbio.2018.04.037

中图分类号：

R318 [生物医学工程];

学科分类号：

0831 ;

摘要：

A multi-drug delivery platform is developed to address current shortcomings of post-operative ocular drug delivery. The sustained biodegradable drug release system is composed of biodegradable polymeric microparticles (MPs) incorporated into a bulk biodegradable hydrogel made from triblock copolymers with poly(ethylene glycol) (PEG) center blocks and hydrophobic biodegradable polyester blocks such as poly(lactide-co-glycolide) (PLGA), Poly(lactic acid) (PLA), or Poly(lactide-co-caprolactone) (PLCL) blocks. This system is engineered to flow as a liquid solution at room temperature for facile injection into the eye and then quickly gel as it warms to physiological body temperatures (approximately 37 degrees C). The hydrogel acts as an ocular depot that can release three different drug molecules at programmed rates and times to provide optimal release of each species. In this manuscript, the hydrogel is configured to release a broad-spectrum antibiotic, a potent corticosteroid, and an ocular hypotensive, three ophthalmic therapeutic agents that are essential for post-operative management after ocular surgery, each drug released at its own timescale. The delivery platform is designed to mimic current topical application of postoperative ocular formulations, releasing the antibiotic for up to a week, and the corticosteroid and the ocular hypotensive agents for at least a month. Hydrophobic blocks, such as PLCL, were utilized to prolong the release duration of the biomolecules. This system also enables customization by being able to vary the initial drug loading to linearly tune the drug dose released, while maintaining a constant drug release profile over time. This minimally invasive biodegradable multi-drug delivery system is capable of replacing a complex ocular treatment regimen with a simple injection. Such a depot system has the potential to increase patient medication compliance and reduce both the immediate and late term complications following ophthalmic surgery. (C) 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

引用

页码：90 / 102

页数：13