Electronic Theses and Dissertations

Date of Award

1-1-2016

Document Type

Dissertation

Degree Name

Ph.D. in Pharmaceutical Sciences

Department

Biomolecular Sciences

First Advisor

S. Narasimha Murthy

Second Advisor

Seongbong Jo

Third Advisor

Dhammika Nanayakkara

Relational Format

dissertation/thesis

Abstract

Topical therapy is commonly used for the treatment of nail diseases such as onychomycosis and nail psoriasis due to less severe side effects, non-invasiveness, direct drug delivery at the site of infection, patient compliance and lower cost of treatment. However, topical treatment is limited due to poor permeability and hard nature of nail plate. The main objective of first project was to investigate the penetrability of apremilast into and across the nail plate, folloby the preparation of a novel nail lacquer formulation to improve its ungual and trans-ungual permeation for the treatment of nail psoriasis. Dexpanthenol and salicylic acid were found to be the potential permeation enhancers. The final nail lacquer formulation shothe ability to form a water resistant film on nail plate and delivered significant amount of apremilast into the nail apparatus. In second project, iontophoresis technique was investigated to improve the ungual and trans-ungual permeation of itraconazole for the treatment of onychomycosis. In vitro and ex vivo permeation studies were performed following two protocols, a) pulse application of iontophoresis for 3 days (8 h/day), b) continuous application of iontophoresis for 24 h. The results of in vitro and ex vivo studies demonstrated the feasibility of iontophoresis technique to enhance nail delivery of itraconazole. Pulsed application of iontophoresis was found to be superior over continuous application of iontophoresis in all cases. In third project, a novel hyponychium pathway was investigated to deliver drugs directly into the ventral layer of nail plate and other part of nail apparatus using iontophoresis as an active technique. In vitro and ex vivo studies resulted that hyponychium pathway can be a viable option to deliver significant amount of drug into nail apparatus by the application of iontophoresis technique. In final project, pre-treatment with solid microneedle was investigated to improve the availability of drugs in nail apparatus. The application of microneedles has not been explored before to improve nail delivery of drugs. Microneedle pre-treatment is a novel approach which has already been used to deliver small and large molecules into the skin in a minimally invasive manner.

Share

COinS
 
 

To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.