Suprachoroidal space-inducing hydrogel-forming microneedles (SI-HFMN): An innovative platform for drug delivery to the posterior segment of the eye

被引:1
作者
Choi, Jaibyung [1 ]
Shim, Suhyeon [1 ]
Shin, Jiwoo [1 ]
Lee, Ahhyun [2 ]
Strang, Jaan [4 ]
Braun, Tobias [4 ]
Naef, Reto [4 ]
Jung, Hyungil [1 ,3 ]
机构
[1] Yonsei Univ, Dept Biotechnol, 50 Yonsei Ro, Seoul 03722, South Korea
[2] Yonsei Univ, Program Integrat Biotechnol, 85 Songdogwahak Ro, Incheon 21983, South Korea
[3] JUVIC Inc, 272 Digital Ro, Seoul 08389, South Korea
[4] TOPADUR Pharm AG, Grabenstr 11A, CH-8952 Schlieren, Switzerland
关键词
Hydrogel-forming microneedle; Suprachoroidal space; Candlelit; Ocular drug delivery; Posterior eye segment; RELEASE;
D O I
10.1016/j.bioactmat.2025.03.024
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
The suprachoroidal space (SCS), which exists between the sclera and choroid, offers a promising delivery route to the posterior segment of the eye (PSE) and is integrated with hollow microneedles (HMNs) for minimally invasive delivery. However, HMNs are limited by backflow owing to their narrow channel. Therefore, this study proposes a biocompatible SCS-inducing hydrogel-forming microneedle (SI-HFMN) with a specially designed candlelit shape that swells to separate the sclera from the choroid. The induced SCS provides a route for delivering loaded drugs to the PSE upon application. The optimized formulation of 20 % (w/w) poly(methyl vinyl ether-alt-maleic acid) (PMVE/MA) crosslinked with 7.5 % (w/w) polyethylene glycol (PEG) possesses sufficient mechanical strength (5.1 +/- 0.7 N) to penetrate both the sclera and swell by 356 +/- 28 %, to mechanically stimulate SCS formation. The formulation also recorded a drug absorption amount of 101 +/- 9 mu g/mg of hydrogel. Furthermore, in vitro and ex vivo experiments demonstrated the ability of the SI-HFMN to deliver drugs to the PSE via the formed SCS. Thus, this system offers an innovative method for drug delivery to PSE by inducing SCS formation.
引用
收藏
页码:47 / 60
页数:14
相关论文
共 52 条
[1]   Polymer based sustained drug delivery to the ocular posterior segment: barriers and future opportunities for the treatment of neovascular pathologies [J].
Alshaikh, Rasha A. ;
Waeber, Christian ;
Ryan, Katie B. .
ADVANCED DRUG DELIVERY REVIEWS, 2022, 187
[2]   Self-Adhesive Microneedles with Interlocking Features for Sustained Ocular Drug Delivery [J].
Amer, Maher ;
Chen, Roland K. .
MACROMOLECULAR BIOSCIENCE, 2020, 20 (06)
[3]   Development and characterization of a dry reservoir-hydrogel-forming microneedles composite for minimally invasive delivery of cefazolin [J].
Bin Sabri, Akmal Hidayat ;
Anjani, Qonita Kurnia ;
Utomo, Emilia ;
Ripolin, Anastasia ;
Donnelly, Ryan F. .
INTERNATIONAL JOURNAL OF PHARMACEUTICS, 2022, 617
[4]   Scleral structure and biomechanics [J].
Boote, Craig ;
Sigal, Ian A. ;
Grytz, Rafael ;
Hua, Yi ;
Nguyen, Thao D. ;
Girard, Michael J. A. .
PROGRESS IN RETINAL AND EYE RESEARCH, 2020, 74
[5]  
Bouma BE, 2022, NAT REV METHOD PRIME, V2, DOI 10.1038/s43586-022-00162-2
[6]   Factors influencing the swelling behaviour of polymethyl vinyl ether-co-maleic acid hydrogels crosslinked by polyethylene glycol [J].
Chandran, Rubhan ;
Tohit, Eusni Rahayu Mohd ;
Stanslas, Johnson ;
Mahmood, Tuan Mazlelaa Tuan ;
Salim, Norazlinaliza .
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY, 2022, 68
[7]  
chemspider, CSID:6075
[8]   IOP Reduction in Nonhuman Primates by Microneedle Injection of Drug-Free Hydrogel to Expand the Suprachoroidal Space [J].
Chung, Yooree G. ;
Fan, Shan ;
Gulati, Vikas ;
Li, Hoi-Lam ;
Gong, Haiyan ;
Toris, Carol B. ;
Prausnitz, Mark R. ;
Ethier, C. Ross .
TRANSLATIONAL VISION SCIENCE & TECHNOLOGY, 2024, 13 (10)
[9]  
Ciulla T, 2022, AM J MANAG CARE, V28, pS243, DOI 10.37765/ajmc.2022.89270
[10]   AAV8-vectored suprachoroidal gene transfer produces widespread ocular transgene expression [J].
Ding, Kun ;
Shen, Jikui ;
Hafiz, Zibran ;
Hackett, Sean F. ;
Silva, Raquel Lima e ;
Khan, Mahmood ;
Lorenc, Valeria E. ;
Chen, Daiqin ;
Chadha, Rishi ;
Zhang, Minie ;
Van Everen, Sherri ;
Buss, Nicholas ;
Fiscella, Michele ;
Danos, Olivier ;
Campochiaro, Peter A. .
JOURNAL OF CLINICAL INVESTIGATION, 2019, 129 (11) :4901-4911