UCLA researchers in the Department of Chemical and Biomolecular Engineering have developed a robust nanoparticle technology for effective, sustained-release ocular drug delivery.
BACKGROUND: Topically applied therapeutics are the common mode of delivery for treating ocular diseases, ranging from chronic conditions like glaucoma to acute inflammation and allergies. Topicals, such as eye drops, are easy to synthesize, cost-effective, and widely available despite their low bioavailability. However, physical barriers within the eye, natural defense mechanisms such as drug-degrading enzymes, and rapid clearance due to tear drainage significantly reduce drug efficacy and penetration. Treatment of diseases such as glaucoma and uveitis require drugs diffusion through the cornea and sclera in order to be effective. To compensate for the <95% loss in the active therapeutic, common prescriptions require both frequent dosing and higher drug concentrations. which can increase toxicity and burden patients. Several alternative ocular drug delivery treatments have incorporated nanotechnology in order to address permeability and bioavailability challenges. Hydrogel, nanoparticles, and combinations of the two have demonstrated improved adhesiveness, biocompatibility, and retention times. Despite these improvements, these technologies have not been clinically adopted as they still require frequent administration for therapeutic efficacy. Further, the use of in situ hydrogels often does not account for the biophysical environment of the tear fluid which causes the solution to become more viscous and nonhomogeneous, which can cause patient discomfort and hinder precise drug release. Thus, there is a need to develop an ideal ocular drug delivery platform with high permeability in the intraocular space, long-lasting bioavailability to reduce dosing frequency, and controlled drug release to minimize off-target toxicity.
INNOVATION: Researchers at UCLA led by Dr. Nasim Annabi (with Dr. Reza Dana of Massachusetts Eye and Ear and Harvard Medical School) have developed a nanoparticle-based drug delivery platform for ocular disease treatment with enhanced bioavailability. They utilize biodegradable Mucus Targeting Particles (MTPs), which are composed of co-polymers with finely tunable nanoscale size, increases permeability and surface area for adhesion. The release rate of the desired drug payload within the hydrophobic core of the MTP can also be adjusted by changing the chemical composition of the co-polymer. Additionally, reactive surface groups enable the nanoparticles to target the epithelial cell surface and covalently bond to surrounding glycoproteins, increasing retention within the mucosal layer. Lastly, the hydrogel polymer matrix containing the MTPs allows for improved penetration and diffusion of the reactive particle by becoming less viscous upon contact with the electrolyte environment of the eye. Thus, this drug delivery platform can serve as a highly efficient and controlled method to deliver drugs for treatment of ocular diseases.
POTENTIAL APPLICATIONS:
- Ocular disease therapeutics (e.g. Glaucoma, diabetic retinopathy, cataracts)
- Improved bioavailability and cell-adhesion nanoparticle drug delivery
ADVANTAGES:
- Decreased application frequency required for eye drop treatment
- Sustained and controlled release of chosen drug
- Increased comfort and decreased patient incompliance from easier drug application
DEVELOPMENT-TO-DATE:
This technology can be reliably synthesized within the target nanoscale range (60 – 150 nm) with sufficient capacity and loading efficiency. The nanoparticles have demonstrated in vitro that they are highly stable at 37 C with a controlled, sustained drug release profile for up to 1 week.
Related Papers (from the inventors only):
Chen Xi et al. Engineering a drug eluting ocular patch for delivery and sustained release of anti-inflammatory therapeutics. AlChE J. 69(6), e18067 (2023)
Gholizadeh S et al. Advanced nanodelivery platforms for topical ophthalmic drug delivery. Drug Discov Today. 26(6), 1437-1449 (2021)
KEYWORDS: Nanoparticle, nanocarriers, nanomedicines, Glaucoma, drug delivery, ocular disorders, ocular drug delivery, eye drops, polymers, ocular inflammation