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Microneedles for transdermal drug de...

Gupta, Jyoti.

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Microneedles for transdermal drug delivery in human subjects.

紀錄類型:	書目-語言資料,印刷品 : Monograph/item
正題名/作者:	Microneedles for transdermal drug delivery in human subjects./
作者:	Gupta, Jyoti.
面頁冊數:	227 p.
附註:	Source: Dissertation Abstracts International, Volume: 71-10, Section: B, page: 6260.
Contained By:	Dissertation Abstracts International71-10B.
標題:	Health Sciences, Pharmacology. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3425089
ISBN:	9781124255897

Microneedles for transdermal drug delivery in human subjects.
Gupta, Jyoti.

Microneedles for transdermal drug delivery in human subjects. - 227 p.

Source: Dissertation Abstracts International, Volume: 71-10, Section: B, page: 6260.

Thesis (Ph.D.)--Georgia Institute of Technology, 2009.

This first aim of this thesis sought to characterize the skin repair responses to microneedle insertion by determining the microneedle and skin condition parameters that affect the duration of enhanced skin permeability using impedance spectroscopy. The study demonstrated for the first time that skin occlusion significantly slowed down skin barrier recovery following microneedle treatment; however, the skin barrier rapidly resealed in the absence of occlusion. This was because skin occlusion blocked the transdermal water gradient within the SC, which is the key signal necessary to facilitate skin barrier repair. The study also revealed that microneedle geometry played a significant role in the skin resealing process in the presence of occlusion such that skin treated with longer, increased number, and larger cross-sectional area needles recovered more slowly under the effect of occlusion. Further, analysis of pain scores revealed that increasing the number of needles and needle cross-sectional area led to slower barrier recovery without significantly affecting pain. This study also led to the development and validation of a pharmacokinetic model to predict transdermal drug delivery in-vivo using skin impedance measurements as the input without any fitted parameters.

ISBN: 9781124255897Subjects--Topical Terms:

1017717
Health Sciences, Pharmacology.

Microneedles for transdermal drug delivery in human subjects.
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500 $a Source: Dissertation Abstracts International, Volume: 71-10, Section: B, page: 6260.
500 $a Adviser: Mark R. Prausnitz.
502 $a Thesis (Ph.D.)--Georgia Institute of Technology, 2009.
520 $a This first aim of this thesis sought to characterize the skin repair responses to microneedle insertion by determining the microneedle and skin condition parameters that affect the duration of enhanced skin permeability using impedance spectroscopy. The study demonstrated for the first time that skin occlusion significantly slowed down skin barrier recovery following microneedle treatment; however, the skin barrier rapidly resealed in the absence of occlusion. This was because skin occlusion blocked the transdermal water gradient within the SC, which is the key signal necessary to facilitate skin barrier repair. The study also revealed that microneedle geometry played a significant role in the skin resealing process in the presence of occlusion such that skin treated with longer, increased number, and larger cross-sectional area needles recovered more slowly under the effect of occlusion. Further, analysis of pain scores revealed that increasing the number of needles and needle cross-sectional area led to slower barrier recovery without significantly affecting pain. This study also led to the development and validation of a pharmacokinetic model to predict transdermal drug delivery in-vivo using skin impedance measurements as the input without any fitted parameters.
520 $a The second part of this thesis studied the effect of microneedle insertion and infusion parameters on the flow conductivity of skin. The study showed for the first time that microneedle-based delivery within the dermis typically led to a decrease in flow conductivity with increasing fluid volume in-vivo. This was due to fluid flow against the dense fibers within the dermis and also due to further compaction of this dense structure through compression at the needle tip. Microneedle retraction, lower infusion flowrates, and the addition of hyaluronidase helped reduce the skin's resistance to flow. Further, analysis of pain scores during infusion demonstrated that microneedles can be used to deliver up to 800 mul of fluid at moderate to high flow rates with significantly less pain than hypodermic needle insertion. Delivery of 1 mL of fluid can be attained with less pain than hypodermic needles at either low flow rates, shallow depths, or through the addition of hyaluronidase.
520 $a The third aim of this thesis studied the efficacy of microneedles for systemic drug delivery effects by delivering insulin to Type 1 diabetes subjects and comparing results to a subcutaneous catheter control. This study was carried out in three steps. The study first determined the optimum microneedle insertion depth for effective insulin delivery by inserting microneedles to different depths within the skin ranging from 1 mm to 5 mm. The 1 mm depth led to the fastest insulin absorption and was then used to determine if intradermal microneedle-based insulin delivery can be used to reduce postprandial glucose levels by delivering a bolus of insulin prior to consumption of a standardized meal. Upon determining that insulin delivery at 1 mm was effective in reducing glucose levels, a more in-depth study involving additional subjects was performed at a depth of 900 mum. This phase of the study demonstrated that intradermal insulin delivery led to faster pharmacokinetics with higher peak insulin concentrations and faster times to reach these peaks while causing tighter glycaemic control. This was due to the rapid absorption of insulin as a result of the microneedles targeting the rich capillary network of the papillary dermis. The study also showed that microneedles caused less pain and irritation than catheters and were preferred by all study subjects.
520 $a The last aim of this thesis studied the efficacy of microneedles for delivery of local therapeutics by delivering lidocaine for local anesthesia. Lidocaine was delivered to the volar forearm skin and the back of the hand of healthy adult subjects to compare the pain and efficacy of microneedle injection with that of traditional hypodermic needle injection. The study results were the first to demonstrate that microneedle-based lidocaine delivery was less painful than and as effective as hypodermic needles in terms of anesthesia onset time, area and depth of analgesia, and lack of pain associated with an intravenous catheter insertion. Further, greater than 77% of the subjects preferred microneedle treatment over hypodermic needles and greater than 82% of the subjects considered microneedles to be not painful. (Abstract shortened by UMI.)
590 $a School code: 0078.
650 4 $a Health Sciences, Pharmacology. $3 1017717
650 4 $a Engineering, Biomedical. $3 1017684
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690 $a 0541
710 2 $a Georgia Institute of Technology. $3 696730
773 0 $t Dissertation Abstracts International $g 71-10B.
790 1 0 $a Prausnitz, Mark R., $e advisor
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791 $a Ph.D.
792 $a 2009
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