Thiolated Hydroxypropyl-β-cyclodextrin: A Potential Multifunctional Excipient for Ocular Drug Delivery.

Patrick Knoll,Angela Fabiano,Brunella Grassiri,Andreas Bernkop-Schnürch,Ylenia Zambito,Anna Maria Piras

doi:10.3390/ijms23052612

Patrick Knoll, Angela Fabiano + Show 4 more

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https://doi.org/10.3390/ijms23052612

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Abstract

The goal of this study was the design and evaluation of a thiolated cyclodextrin providing high drug solubilizing and mucoadhesive properties for ocular drug delivery. Hydroxypropyl-β-cyclodextrin (HP-β-CD) was thiolated via a microwave-assisted method, resulting in a degree of thiolation of 33%. Mucoadhesive properties of thiolated HP-β-CD (HP-β-CD-SH) were determined via rheological measurements and ex vivo studies on isolated porcine cornea. Due to thiolation of HP-β-CD, a 2-fold increase of mucus viscosity and a 1.4-fold increase in residence time on isolated corneal tissue were achieved. After instillation, the mean precorneal residence time and AUC of dexamethasone (DMS) eye drops were 4-fold and 11.7-fold enhanced by HP-β-CD-SH, respectively. Furthermore, in the presence of HP-β-CD-SH, a constant high level of DMS in aqueous humour between 30 and 150 min after administration was observed. These results suggest that HP-β-CD-SH is an excellent excipient for ocular formulations of poorly soluble drugs in order to prolong their ocular residence time and bioavailability.

Highlights

Academic Editor: Sharmila MasliThe therapeutic efficacy of many active pharmaceutical ingredients being in use to cure eye diseases is limited by a poor bioavailability that is often less than 5%
Strategies to prolong the precorneal residence time are primarily focusing on the use of mucoadhesive polymers
These auxiliary agents, cause an impaired vision, do not properly distribute over the ocular surface when used in higher concentrations and cannot improve the solubility of hydrophobic drugs

Summary

Introduction

Academic Editor: Sharmila MasliThe therapeutic efficacy of many active pharmaceutical ingredients being in use to cure eye diseases is limited by a poor bioavailability that is often less than 5%. The main reason for this poor ocular bioavailability is a short drug residence time of a few minutes in the precorneal region, that is too short for absorption or for a therapeutic effect [1]. Strategies to prolong the precorneal residence time are primarily focusing on the use of mucoadhesive polymers. These auxiliary agents, cause an impaired vision, do not properly distribute over the ocular surface when used in higher concentrations and cannot improve the solubility of hydrophobic drugs. In order to address these shortcomings of mucoadhesive polymers, thiolated cyclodextrins were introduced as an ‘invisible choice’ to prolong ocular residence time of poorly soluble drugs [2].

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