【Paper】A Macrolide-loaded Nanofiber Insert for Sustainable Intraocular Administration Based on Polycaprolactone and Cellulose Acetate: A Pharmacokinetic Study in the Rabbit Eye

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A Macrolide-loaded Nanofiber Insert for Sustainable Intraocular Administration Based on Polycaprolactone and Cellulose Acetate: A Pharmacokinetic Study in the Rabbit Eye

Bioavailability and DDS

Azithromycin (AZM) is a broad-spectrum antibiotic that has anti-inflammatory properties and is used as an ophthalmic agent to treat ocular infections because it acts to cause bacterial conjunctivitis.

However, eyedrops have limited bioavailability and require frequent administration. Therefore, in recent years, nano-based novel drug delivery systems that can increase corneal permeation and enhance drug residence lengthening and drug delivery have attracted attention.

Bioavailability: an indicator of how well a given drug (formulation) reaches and acts in the systemic circulation.

Effectiveness and Prospect of Eye Points by DDS Using Nanofibers

Among these methods, the use of nanofibers has characteristics such as high surface area, porous structure, and high drug loading capacity, making it possible to insert nanofibers directly into the conjunctive sac to extend drug residence time at the surface of the conjunctive membrane, and reducing the number of drug dosing, making it one of the most suitable methods for eye-sustaining drug delivery.

In practice, a large number of polymers are processed into nanofibers using the electrospinning method.

We used cellulose acetate (CA), which is non-toxic, biodegradable, and biocompatible, and polycaprolactone (PCL), a hydrophobic polymer that has received FDA approval for drug delivery, to fabricate nanofibers loaded with AZM and evaluated their efficacy.

Since they used to fabricate AZM loaded nanofibers with hydrophilic polymers, they have also evaluated improvements in their pharmaceutical kinetic properties compared to previous studies.

The nanofibers produced this time were made with a thickness 0.11mm less than that suitable for immobilization on a sac and that does not stimulate the cornea or condyle. From the results of physical characterization, it was found that it has sufficient flexibility and suitable strength, and is stable even under dry and humid conditions, and suitable for various processes and handling.

In the drug release test in in vitro, slow drug release was observed in CA, and high-concentration drug release was observed in the early stage in PCL. In addition, the greater the amount of drug contained in nanofibers, the greater the area that inhibits cell growth. Both CA, PCL are biocompatible, so no cytotoxicity was observed.

In in vivo study, when AZM doped nanofibers were inserted into rabbit conjunctions, both CA, PCL were non-irritant, and showed a drug residence time longer than eyedrops and a maximal drug release concentration of about 20 times, with a particularly long mean residence time in CA, and a particularly high drug release concentration in PCL. In this study, AZM indicated that it was detectable in tear fluid for more than 6 days and that drug release from the formulation was controlled.

Compared with previous studies, both nanofibers had improved drug-kinetic properties, probably due to their ability to encapsulate the drug within a hydrophobic nanofiber matrix.

All of these findings suggest that the newly fabricated nanofibers can contribute to the improvement of treatment effectiveness with AZM ocular administration by enabling the continuous release of agents for the treatment of superficial microbial episodes and by improving patient-compliance through reduced frequency of dosing.

References: A Macrolide-loaded Nanofiber Insert for Sustainable Intraocular Administration Based on Polycaprolactone and Cellulose Acetate: A Pharmacokinetic Study in the Rabbit Eye
Shiva Taghe (A,B) , Shahla Mirzaeei (B,A) , Negin Pakdaman (C) , Aliakbar Kazemi (C) , Ali Nokhodchi (D).
A:Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
B:Nano Drug Delivery Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
C:Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran
D:Pharmaceutics Research Laboratory, School of Life Sciences, University of Sussex, Brighton, UK