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Embeddable sustained-release microneedles for intradermal contraceptive delivery

Al Dalaty, Adnan 2022. Embeddable sustained-release microneedles for intradermal contraceptive delivery. PhD Thesis, Cardiff University.
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Abstract

There is still an emerging need for effective, accessible and convenient contraception methods, particularly in low resource countries. About 923 million (> 50%) of reproductive-aged women living in low- and middle-income countries attempted to prevent pregnancy in 2019, however, 218 million among them did not have access to any form of modern contraceptives. Providing women of reproductive age with access to family planning services is a fundamental human right and allows them to decide freely on whether and when they want to have children, and how many children they have. Addressing this unmet need would reduce the incidence of unintended pregnancies and improve maternal and child health. Commercially-available long-acting reversible contraceptives (LARCs), such as subcutaneous implants (up to 5-7 years activity) and intramuscular injectables (3 months activity), maintain controlled daily release of hormones; thus, offer improved user compliance and convenience. They require however painful invasive administration and, in the case of implants, removal, typically by skilled healthcare professionals and generate biohazardous sharps waste. Microneedles are micron-scaled projections designed to puncture the uppermost layer of skin, stratum corneum, to facilitate transdermal or intradermal delivery of therapeutics into the cutaneous compartment, in a painless and blood-free manner. This thesis aims to develop an alternative method of contraception whereby the contraceptive is delivered into skin using microneedles which slowly degrade to provide 6-months contraceptive activity. Two biodegradable microneedle designs were manufactured by academic and industrial project partners. Candidate polymer formulations for the biodegradable microneedles were loaded with a synthetic progestin, levonorgestrel, and characterised for drug release kinetics. These studies were performed in conventional drug release media and a novel media supplemented with human skin homogenate. The use of these media, accompanied by sensitive and selective drug extraction and analytical protocols, enabled the characterisation of levonorgestrel release in a more biologically relevant environment. Sustained release kinetics of levonorgestrel were achieved from different biodegradable formulations in both media over a period of up to 9 months. The skin insertion performance of polymer only and levonorgestrel loaded biodegradable microneedles was assessed using human and porcine skin explants. In these studies, MN deployment was facilitated using several prototype applicator devices. Skin puncture experiments in ex vivo skin demonstrated that microneedles had sufficient tip sharpness and mechanical robustness to penetrate the skin surface. Microneedle performance varied between the polymer only and levonorgestrel loaded microneedles, with the microneedle composition and design, as well as the applicator mechanism, playing a key role in determining their efficiency. In conclusion, this thesis explored two novel designs of biodegradable polymer MNs to address the unmet need for contraception in low resource countries. The MN systems developed in this project hold great promise for sustained intradermal delivery of contraceptives for 6-months activity. This could provide an intermediate option to existing LARCs which have shorter, e.g. 3 months (intramuscular injections), or longer, e.g. 5-7 years (hormonal subcutaneous implants and intrauterine systems) duration of action. This MN-mediated contraceptive approach is also anticipated to improve user acceptability and compliance.

Item Type: Thesis (PhD)
Date Type: Completion
Status: Unpublished
Schools: Pharmacy
Subjects: Q Science > Q Science (General)
Date of First Compliant Deposit: 24 May 2022
Last Modified: 24 May 2022 10:09
URI: https://orca.cardiff.ac.uk/id/eprint/149963

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