John Garner

Thermogelling PLGA-PEG-PLGA from PolySciTech used in development of ocular RNA-nanoparticle delivery system

Blog Post created by John Garner on Nov 28, 2017

PLGA-PEG-PLGA ocular RNA injection.jpg

Delivering drugs to the human eye presents a unique set of challenges. Since the injection volume is extremely low and the surrounding tissue is extremely sensitive, care must be taken to use biocompatible carriers with high payload. One means to do this is to use nanoparticles while another is to use thermogelling polymers (ie polymers which transition from a liquid solution at room temperature to a solid gel at body temperature). A powerful delivery technique is to load nanoparticles inside of thermogelling polymers so as to control the release of the nanoparticles. Recently, Researchers at University of Cincinnati, Silpakorn University, Indiana University, and The Ohio State University used PLGA-PEG-PLGA (PolyVivo AK024, AK097) from PolySciTech (www.polyscitech.com) to entrap RNA-nanoparticles and track their distribution in the eye. This research holds promise for providing for more effective ocular drug-delivery. Read more: Shi, Zhanquan, S. Kevin Li, Ponwanit Charoenputtakun, Chia-Yang Liu, Daniel Jasinski, and Peixuan Guo. "RNA nanoparticle distribution and clearance in the eye after subconjunctival injection with and without thermosensitive hydrogels." Journal of Controlled Release (2017). https://www.sciencedirect.com/science/article/pii/S0168365917310246

 

“Abstract: Thermodynamically and chemically stable RNA nanoparticles derived from the three-way junction (3WJ) of the pRNA from bacteriophage phi29 were examined previously for ocular delivery. It was reported that RNA nanoparticles with tri-way shape entered the corneal cells but not the retinal cells, whereas particle with four-way shape entered both corneal and retinal cells. The present study evaluated ocular delivery of RNA nanoparticles with various shapes and sizes, and assessed the effect of thermosensitive hydrogels (poly(lactic-co-glycolic acid)-b-poly(ethylene glycol)-b-poly(lactic-co-glycolic acid); PLGA-PEG-PLGA) for increasing the retention of RNA nanoparticles in the eye. Fluorescence imaging of mouse eyes and fluorescence microscopy of dissected eye tissues from the conjunctiva, cornea, retina, and sclera were performed to determine the distribution and clearance of the nanoparticles in the eyes after subconjunctival injection in vivo. RNA nanoparticles entered the cells of the conjunctiva, cornea, retina, and sclera after subconjunctival delivery. The clearance of RNA pentagon was slower than both RNA square and triangle of the same designed edge length (10 nm) in the eye, and the clearance of RNA squares of the longer edge lengths (10 and 20 nm) was slower than RNA square of the shorter edge length (5 nm), this indicating that the size could affect ocular pharmacokinetics of the nanoparticles. At 24 h after the injection, approximately 6–10% of the fluorescence signal from the larger nanoparticles in the study (RNA square of 20 nm edge length and RNA pentagon of 10 nm edge length) remained in the eye, and up to 70% of the retinal cells contained the nanoparticles. The results suggest that the larger nanoparticles were “gulped” in conjunctival, corneal, retinal, and scleral cells, similar to the behavior observed in macrophages. Additionally, the combination of RNA nanoparticles with the thermosensitive polymers increased the retention of the nanoparticles in the eye. Keywords: RNA nanoparticle; Double-stranded RNA; Temperature sensitive polymer; Subconjunctival; Ocular delivery”

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