A novel technology using transscleral ultrasound to deliver protein loaded nanoparticles.
This study was designed to investigate the feasibility of silk fibroin nanoparticles (SFNs) for sustained drug delivery in transscleral ultrasound. Fluorescein isothiocynate labeled bovine serum albumin (FITC-BSA, MW 66.45 kDa) was chosen as a model macromolecular protein drug and SFNs were used as nano-carrier systems suitable for ocular drug delivery. Drug loaded nanoparticles (FITC-BSA-SFNs) were first prepared and characterized. In vitro transscleral study under ultrasound exposure (1MHz, 0.5 W/cm(2), 5 min continuous wave) using isolated sclera of rabbit was performed. The posterior eye segment of rabbit was examined for adverse effect by slit-lamp and histology. It was found that FITC-BSA-SFNs possessed sustained release, bioadhesive, and co-permeation characteristics. The ultrasound application significantly improved the penetration efficiency of FITC-BSA-SFNs as compared with passive delivery, meanwhile caused no damages to the ocular tissue and particles themselves. The distribution profile of SFNs revealed rapid and lasting adhesion on the outer scleral tissues, followed by migration into the interior up to one week after treatment. This research suggested a novel non-invasive transscleral administration of macromolecular protein drugs using SFN carriers combining with ultrasound technology.
School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
Di
D
Huang
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.
Lili
L
Wang
School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China; Research and Development Center of Pharmaceutical Engineering, Sun Yat-sen University, Guangzhou, China.
Yixuan
Y
Dong
School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China. Electronic address: pxin_1385@163.com.
Xin
X
Pan
Guangzhou Neworld Pharm. Co. Ltd., Guangzhou, China.
Ge
G
Li
School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China; Research and Development Center of Pharmaceutical Engineering, Sun Yat-sen University, Guangzhou, China; Guangdong Research Center for Drug Delivery Systems, Guangzhou, China. Electronic address: chuanbin_wu@126.com.
Chuanbin
C
Wu
D000287:Administration, Topical; D000818:Animals; D002417:Cattle; D002942:Circular Dichroism; D016503:Drug Delivery Systems; D005123:Eye / Q000187:drug effects*; D005349:Fibroins / Q000737:chemistry; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives / Q000737:chemistry; D046911:Macromolecular Substances / Q000737:chemistry; D008856:Microscopy, Fluorescence; D053758:Nanoparticles / Q000737:chemistry; D010316:Particle Size; D010539:Permeability; D017433:Protein Structure, Secondary; D011506:Proteins / Q000008:administration & dosage* / Q000737:chemistry; D011817:Rabbits; D012590:Sclera / Q000187:drug effects*; D012710:Serum Albumin, Bovine / Q000737:chemistry; D017550:Spectroscopy, Fourier Transform Infrared; D013696:Temperature; D014465:Ultrasonics
D046911:Macromolecular Substances; D011506:Proteins; C039217:fluorescein isothiocyanate bovine serum albumin; D012710:Serum Albumin, Bovine; D005349:Fibroins; D016650:Fluorescein-5-isothiocyanate
Macromolecular protein drugs; Nanoparticles; Non-invasive technology; Silk fibroin; Transsclera; Ultrasound