Nanoparticle Technologies: Enablers for Ocular Drug Delivery

Introduction

As we continue to discover new and innovative small molecules and therapeutic compounds, over 80% of those candidates in drug pipeline are challenging to development due to their poor solubility and bioavailability.¹ There are several ocular barriers such as tear film, corneal, conjunctival and blood barriers that cause the bioavailability issues.² A nanotechnology-based drug delivery system (NODS) remains the acceptable and effective ways for ocular administration of drugs.³

This article will describe the basic understanding of challenges in ocular drug delivery and the future trends in development of innovative drugs.

Ocular Delivery

Figure 1 shows the route of administration of the drug in the eyes. Those include topical, subconjunctival injection, intravitreal injection, retrobulbar injection, intracameral injection. The topical route, however, is non-invasive, widely used, and remains a self-administrative route. The challenges involve the immediate clearance of drugs by spillage and tear drainage that lead to reduced bioavailability.

The topical route of administration allows only a limited amount of drug to permeate through precorneal surface. It helps cross permeation of drugs through cornea to aqueous by passive transcellular pathway. It is, however, limited by the membrane tight junctions that allow only 5% of drug absorption.⁴

Excipients and Polymers for Ocular Delivery

A. Lipids: DSPC, DPPC, DMPC, DOPC, DPPE, Soy lipids, DSPE-mPEG 2000; Cationic lipids (DOTAP) among others.

B. Oils/Glycerides/Surfactants: Mono-, di- and triglycerides, fatty acids; castor oil, polyoxyl 40 hydrogenated castor oil, polyoxyl 35 castor oil, polyoxyl 15 hydroxystearate, polysorbate 80, vitamin E-TPGS, Poloxamer 407, Poloxamer 188, Transcutol, among others.

C. Polymers: PLGA, PCL, PVA, HPMC, HPC, povidone, copovidone, Soluplus, carboxymethyl sodium, chitosan, hyaluronic acid, alginate, gellan gum, among others.

Lipid nanoparticles as vehicles for ocular delivery – Saturated lipid nanoparticles, nanostructured lipid carriers, liposomes, cubosomes, micro- and nanoemulsions; nanosuspensions, dendrimers, micelles among others a range of carriers for ocular or ophthalmic delivery. Table 1 cites many examples of drugs investigated by ocular delivery.^5-18

Ocular Approved Drugs

Several drugs have been approved employing the nanoparticle technologies for the treatment of diseases affecting the anterior segment of the eye as shown in Table 2.³

Conclusion and Future Perspectives

Ocular drug delivery is challenging due to many anatomical barriers. Nanoparticle technologies in ocular delivery, however, have demonstrated wide utilities across all molecules, small and large. We believe that nanoparticle technology will gain steam in ocular delivery for launch of new molecules to market with more innovative polymeric and lipid assemblies.

Ascendia’s platform technologies, NanoSol® (nanosuspension), EmulSol® (microemulsion) and LipidSol® (lipid nanoparticles) are primed to address the challenges with poorly soluble drugs. For instance, Ascendia® using its EmulSol technology, by top down or bottom-up approach has enabled the manufacturing of nanoparticle formulations with controlled particle sizes (< 50 nm) comprised of 0.05% Cyclosporine A, soybean oil, lecithin, and polysorbate 80.¹⁹ With its cGMP manufacturing capabilities of sterile drug products, Ascendia is poised to tackle the challenges to address the unmet medical needs by designing better and smarter polymeric and lipid nanoparticle formulations in the future.

References

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Author Details 

Shaukat Ali, PhD and Jim Huang, PhD, Ascendia® Pharmaceuticals, Inc.

Publication Details 

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