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Development of Microneedle Devices for Drug Delivery / OLIVIA HOWELLS

Swansea University Author: OLIVIA HOWELLS

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DOI (Published version): 10.23889/SUthesis.58289

Abstract

There are numerous modes of therapeutic administration, of which oral delivery is the most convenient and conventional as it involves administration of therapeutics in the form of liquids or solid capsules and tablets. However, this mode encounters several challenges, such as chemical processes with...

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Published: Swansea 2021
Institution: Swansea University
Degree level: Doctoral
Degree name: Ph.D
Supervisor: Guy, Owen ; Sharma, Sanjiv
URI: https://cronfa.swan.ac.uk/Record/cronfa58289
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first_indexed 2021-10-11T10:01:51Z
last_indexed 2021-10-12T03:24:28Z
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To overcome these issues, transdermal drug administration in the form of hypodermic needles, topical creams, and transdermal patches have been employed. However, the effect of transdermal administration is limited due the stratum corneum layer of the skin, which acts as a lipophilic and hydrophobic barrier preventing external molecules from entering the skin. Therefore, hypodermic needles are used due to their sharp tip facilitating penetration through the stratum corneum to deposit the drug formulation into the skin, subcutaneous fat, or muscles layers. However, these needles induce needle-phobia and reduce patient compliance due to the complexity with administration and pain associated with injection. Microneedle devices have been developed to avoid these issues and provide enhanced transdermal therapeutic drug delivery in a minimally invasive manner to eliminate the first-pass metabolism and provide a sustained release. Unlike hypodermic needles injection, they do not cause pain and related fear or phobia in individuals, thereby improving compliance to the prescribed dosage regime. Till now different types of microneedles have been fabricated. These include, solid, coated, hollow and dissolvable, where each type has its own advantages and unique properties and designs. In this thesis, two novel methods utilising silicon etching processes, for the fabrication of both out-of-plane and in-plane silicon microneedles are presented. Hollow out-of-plane microneedles are manufactured through deep reactive-ion etching (DRIE) technology. The patented three-step process flow has been developed to produce multiple arrays of sharp bevelled tipped, hollow microneedles which facilitate easy insertion and controlled fluid injection into excised skin samples. The in-plane microneedles have been fabricated from simultaneous wet KOH etching of the front and reverse of (100) orientated silicon wafers. The characteristic 54.7˚ sidewall etch angle was utilised to form a sharp six-sided microneedle tip and hexagonal shaped shaft. Employing this method allowed fabrication of both solid and hollow microneedles with different geometries i.e., widths and heights of several µm, to determine the optimal MN height and width for effective penetration and transdermal drug delivery. All microneedles fabricated during the PhD studentship tenure have been characterised through histology, fluorescent studies, and delivery into ex-vivo porcine and human skin tissue (research ethics committee reference 08/WSE03/55) to demonstrate effective microneedle based transdermal therapeutic drug delivery. The transdermal delivery of insulin and hyaluronic acid has been successfully demonstrated by employing a simple poke and patch application technique, presenting a clinical improvement over traditional application such as creams and ointments.</abstract><type>E-Thesis</type><journal/><volume/><journalNumber/><paginationStart/><paginationEnd/><publisher/><placeOfPublication>Swansea</placeOfPublication><isbnPrint/><isbnElectronic/><issnPrint/><issnElectronic/><keywords>Miconeedles, drug delivery, fabrication</keywords><publishedDay>13</publishedDay><publishedMonth>7</publishedMonth><publishedYear>2021</publishedYear><publishedDate>2021-07-13</publishedDate><doi>10.23889/SUthesis.58289</doi><url/><notes>A selection of third party content is redacted or is partially redacted from this thesis due to copyright restrictions.</notes><college>COLLEGE NANME</college><CollegeCode>COLLEGE CODE</CollegeCode><institution>Swansea University</institution><supervisor>Guy, Owen ; Sharma, Sanjiv</supervisor><degreelevel>Doctoral</degreelevel><degreename>Ph.D</degreename><degreesponsorsfunders>KESS II; Welsh Government’s European Social Fund (ESF) convergence programme for West Wales and the Valleys</degreesponsorsfunders><apcterm/><funders/><projectreference/><lastEdited>2024-07-11T14:20:30.4040785</lastEdited><Created>2021-10-11T10:57:31.8533443</Created><path><level id="1">Faculty of Science and Engineering</level><level id="2">School of Aerospace, Civil, Electrical, General and Mechanical Engineering - Electronic and Electrical Engineering</level></path><authors><author><firstname>OLIVIA</firstname><surname>HOWELLS</surname><order>1</order></author></authors><documents><document><filename>58289__21133__47c03cf3dfb743f1b65df222d1631c52.pdf</filename><originalFilename>Howells_Olivia_PhD_Thesis_Final_Redacted.pdf</originalFilename><uploaded>2021-10-11T11:57:47.9089609</uploaded><type>Output</type><contentLength>18732381</contentLength><contentType>application/pdf</contentType><version>Redacted version - open access</version><cronfaStatus>true</cronfaStatus><embargoDate>2023-07-08T00:00:00.0000000</embargoDate><documentNotes>Copyright: The author, Olivia Howells, 2021.</documentNotes><copyrightCorrect>true</copyrightCorrect><language>eng</language></document></documents><OutputDurs/></rfc1807>
spelling v2 58289 2021-10-11 Development of Microneedle Devices for Drug Delivery e9740815207f75b60f6beff545696cf1 OLIVIA HOWELLS OLIVIA HOWELLS true false 2021-10-11 There are numerous modes of therapeutic administration, of which oral delivery is the most convenient and conventional as it involves administration of therapeutics in the form of liquids or solid capsules and tablets. However, this mode encounters several challenges, such as chemical processes within the gastrointestinal track and first pass metabolism which subsequently reduce the efficacy of the therapeutic drugs. To overcome these issues, transdermal drug administration in the form of hypodermic needles, topical creams, and transdermal patches have been employed. However, the effect of transdermal administration is limited due the stratum corneum layer of the skin, which acts as a lipophilic and hydrophobic barrier preventing external molecules from entering the skin. Therefore, hypodermic needles are used due to their sharp tip facilitating penetration through the stratum corneum to deposit the drug formulation into the skin, subcutaneous fat, or muscles layers. However, these needles induce needle-phobia and reduce patient compliance due to the complexity with administration and pain associated with injection. Microneedle devices have been developed to avoid these issues and provide enhanced transdermal therapeutic drug delivery in a minimally invasive manner to eliminate the first-pass metabolism and provide a sustained release. Unlike hypodermic needles injection, they do not cause pain and related fear or phobia in individuals, thereby improving compliance to the prescribed dosage regime. Till now different types of microneedles have been fabricated. These include, solid, coated, hollow and dissolvable, where each type has its own advantages and unique properties and designs. In this thesis, two novel methods utilising silicon etching processes, for the fabrication of both out-of-plane and in-plane silicon microneedles are presented. Hollow out-of-plane microneedles are manufactured through deep reactive-ion etching (DRIE) technology. The patented three-step process flow has been developed to produce multiple arrays of sharp bevelled tipped, hollow microneedles which facilitate easy insertion and controlled fluid injection into excised skin samples. The in-plane microneedles have been fabricated from simultaneous wet KOH etching of the front and reverse of (100) orientated silicon wafers. The characteristic 54.7˚ sidewall etch angle was utilised to form a sharp six-sided microneedle tip and hexagonal shaped shaft. Employing this method allowed fabrication of both solid and hollow microneedles with different geometries i.e., widths and heights of several µm, to determine the optimal MN height and width for effective penetration and transdermal drug delivery. All microneedles fabricated during the PhD studentship tenure have been characterised through histology, fluorescent studies, and delivery into ex-vivo porcine and human skin tissue (research ethics committee reference 08/WSE03/55) to demonstrate effective microneedle based transdermal therapeutic drug delivery. The transdermal delivery of insulin and hyaluronic acid has been successfully demonstrated by employing a simple poke and patch application technique, presenting a clinical improvement over traditional application such as creams and ointments. E-Thesis Swansea Miconeedles, drug delivery, fabrication 13 7 2021 2021-07-13 10.23889/SUthesis.58289 A selection of third party content is redacted or is partially redacted from this thesis due to copyright restrictions. COLLEGE NANME COLLEGE CODE Swansea University Guy, Owen ; Sharma, Sanjiv Doctoral Ph.D KESS II; Welsh Government’s European Social Fund (ESF) convergence programme for West Wales and the Valleys 2024-07-11T14:20:30.4040785 2021-10-11T10:57:31.8533443 Faculty of Science and Engineering School of Aerospace, Civil, Electrical, General and Mechanical Engineering - Electronic and Electrical Engineering OLIVIA HOWELLS 1 58289__21133__47c03cf3dfb743f1b65df222d1631c52.pdf Howells_Olivia_PhD_Thesis_Final_Redacted.pdf 2021-10-11T11:57:47.9089609 Output 18732381 application/pdf Redacted version - open access true 2023-07-08T00:00:00.0000000 Copyright: The author, Olivia Howells, 2021. true eng
title Development of Microneedle Devices for Drug Delivery
spellingShingle Development of Microneedle Devices for Drug Delivery
OLIVIA HOWELLS
title_short Development of Microneedle Devices for Drug Delivery
title_full Development of Microneedle Devices for Drug Delivery
title_fullStr Development of Microneedle Devices for Drug Delivery
title_full_unstemmed Development of Microneedle Devices for Drug Delivery
title_sort Development of Microneedle Devices for Drug Delivery
author_id_str_mv e9740815207f75b60f6beff545696cf1
author_id_fullname_str_mv e9740815207f75b60f6beff545696cf1_***_OLIVIA HOWELLS
author OLIVIA HOWELLS
author2 OLIVIA HOWELLS
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publishDate 2021
institution Swansea University
doi_str_mv 10.23889/SUthesis.58289
college_str Faculty of Science and Engineering
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hierarchy_top_id facultyofscienceandengineering
hierarchy_top_title Faculty of Science and Engineering
hierarchy_parent_id facultyofscienceandengineering
hierarchy_parent_title Faculty of Science and Engineering
department_str School of Aerospace, Civil, Electrical, General and Mechanical Engineering - Electronic and Electrical Engineering{{{_:::_}}}Faculty of Science and Engineering{{{_:::_}}}School of Aerospace, Civil, Electrical, General and Mechanical Engineering - Electronic and Electrical Engineering
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description There are numerous modes of therapeutic administration, of which oral delivery is the most convenient and conventional as it involves administration of therapeutics in the form of liquids or solid capsules and tablets. However, this mode encounters several challenges, such as chemical processes within the gastrointestinal track and first pass metabolism which subsequently reduce the efficacy of the therapeutic drugs. To overcome these issues, transdermal drug administration in the form of hypodermic needles, topical creams, and transdermal patches have been employed. However, the effect of transdermal administration is limited due the stratum corneum layer of the skin, which acts as a lipophilic and hydrophobic barrier preventing external molecules from entering the skin. Therefore, hypodermic needles are used due to their sharp tip facilitating penetration through the stratum corneum to deposit the drug formulation into the skin, subcutaneous fat, or muscles layers. However, these needles induce needle-phobia and reduce patient compliance due to the complexity with administration and pain associated with injection. Microneedle devices have been developed to avoid these issues and provide enhanced transdermal therapeutic drug delivery in a minimally invasive manner to eliminate the first-pass metabolism and provide a sustained release. Unlike hypodermic needles injection, they do not cause pain and related fear or phobia in individuals, thereby improving compliance to the prescribed dosage regime. Till now different types of microneedles have been fabricated. These include, solid, coated, hollow and dissolvable, where each type has its own advantages and unique properties and designs. In this thesis, two novel methods utilising silicon etching processes, for the fabrication of both out-of-plane and in-plane silicon microneedles are presented. Hollow out-of-plane microneedles are manufactured through deep reactive-ion etching (DRIE) technology. The patented three-step process flow has been developed to produce multiple arrays of sharp bevelled tipped, hollow microneedles which facilitate easy insertion and controlled fluid injection into excised skin samples. The in-plane microneedles have been fabricated from simultaneous wet KOH etching of the front and reverse of (100) orientated silicon wafers. The characteristic 54.7˚ sidewall etch angle was utilised to form a sharp six-sided microneedle tip and hexagonal shaped shaft. Employing this method allowed fabrication of both solid and hollow microneedles with different geometries i.e., widths and heights of several µm, to determine the optimal MN height and width for effective penetration and transdermal drug delivery. All microneedles fabricated during the PhD studentship tenure have been characterised through histology, fluorescent studies, and delivery into ex-vivo porcine and human skin tissue (research ethics committee reference 08/WSE03/55) to demonstrate effective microneedle based transdermal therapeutic drug delivery. The transdermal delivery of insulin and hyaluronic acid has been successfully demonstrated by employing a simple poke and patch application technique, presenting a clinical improvement over traditional application such as creams and ointments.
published_date 2021-07-13T14:20:29Z
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score 11.016235

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