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Dissolving microneedles for cutaneou...

Chu, Leonard Yi.

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Dissolving microneedles for cutaneous drug and vaccine delivery .

紀錄類型:	書目-語言資料,印刷品 : Monograph/item
正題名/作者:	Dissolving microneedles for cutaneous drug and vaccine delivery ./
作者:	Chu, Leonard Yi.
面頁冊數:	168 p.
附註:	Source: Dissertation Abstracts International, Volume: 72-06, Section: B, page: .
Contained By:	Dissertation Abstracts International72-06B.
標題:	Engineering, Biomedical. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3451227
ISBN:	9781124564685

Dissolving microneedles for cutaneous drug and vaccine delivery .
Chu, Leonard Yi.

Dissolving microneedles for cutaneous drug and vaccine delivery . - 168 p.

Source: Dissertation Abstracts International, Volume: 72-06, Section: B, page: .

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

Currently, biopharmaceuticals including vaccines, proteins, and DNA are delivered almost exclusively through the parenteral route using hypodermic needles. However, injection by hypodermic needles generates pain and causes bleeding. The needle itself poses risk of needle-stick injury. Disposal of these needles also produces biohazardous sharp waste. An alternative delivery tool called microneedles may solve these issues. Ideally, a skin delivery system should (i) deliver a broad range of therapeutics including chemical compounds, macromolecules and biologics, (ii) have a controlled dose with high bioavailability, (iii) be safe, (iv) be simple to use, and (v) be inexpensive. Current microneedle systems have addressed some of the requirements described above, but further characterizations and improvements are still needed. This project focused on one type of microneedles in which the needle tips dissolve upon insertion into the skin. The goal was to design and optimize dissolving microneedle fabrication processes for efficient drug and vaccine delivery to skin. This project also covered the formulation design and drying process for optimal vaccine stability. Finally, the microneedles were tested in vivo for influenza immunization.

ISBN: 9781124564685Subjects--Topical Terms:

1017684
Engineering, Biomedical.

Dissolving microneedles for cutaneous drug and vaccine delivery .
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100 1 $a Chu, Leonard Yi. $3 1676146
245 1 0 $a Dissolving microneedles for cutaneous drug and vaccine delivery .
300 $a 168 p.
500 $a Source: Dissertation Abstracts International, Volume: 72-06, Section: B, page: .
500 $a Adviser: Mark Prausnitz.
502 $a Thesis (Ph.D.)--Georgia Institute of Technology, 2009.
520 $a Currently, biopharmaceuticals including vaccines, proteins, and DNA are delivered almost exclusively through the parenteral route using hypodermic needles. However, injection by hypodermic needles generates pain and causes bleeding. The needle itself poses risk of needle-stick injury. Disposal of these needles also produces biohazardous sharp waste. An alternative delivery tool called microneedles may solve these issues. Ideally, a skin delivery system should (i) deliver a broad range of therapeutics including chemical compounds, macromolecules and biologics, (ii) have a controlled dose with high bioavailability, (iii) be safe, (iv) be simple to use, and (v) be inexpensive. Current microneedle systems have addressed some of the requirements described above, but further characterizations and improvements are still needed. This project focused on one type of microneedles in which the needle tips dissolve upon insertion into the skin. The goal was to design and optimize dissolving microneedle fabrication processes for efficient drug and vaccine delivery to skin. This project also covered the formulation design and drying process for optimal vaccine stability. Finally, the microneedles were tested in vivo for influenza immunization.
520 $a The first goal was to develop new dissolving microneedle design and fabrication process for controlled drug loading, drug encapsulation and delivery with enhanced bioavailability in the skin. Due to the use of aqueous-based excipients for microneedle matrix, undesired drug diffusion within microneedles could occur during fabrication. To achieve high bioavailability, novel fabrication methods were developed to control drug diffusion by localizing the drug only in the microneedle tips. Deeper microneedle insertion was achieved by incorporating a pedestal for enhanced bioavailability.
520 $a The second part of the project focused on developing a new dissolving microneedle system called arrowhead microneedles. The key advantages of arrowhead microneedles include short administration time on the scale of seconds, full insertion of the needle tips into the skin and leaving no biohazardous sharp waste after use. Arrowhead microneedles could fully deposit the tips containing drug within the skin for expedited delivery. This rapid delivery could be achieved by two mechanisms: One relied on gradual dissolution of the tips within the skin; another one used mechanical force to separate the tips from the shafts. Upon insertion, the sharp microneedle tips were embedded within the skin while the dull shafts and backing could be quickly removed and disposed without concerns for needle stick injury and generation of biohazardous sharp waste.
520 $a After optimizing dissolving microneedle fabrication, structural design and delivery, we wanted to ensure the encapsulated molecules within microneedles remained stable. We encapsulated inactivated influenza virus within the dissolving microneedles made of a novel formulation consisting of polyvinyl alcohol and sucrose. The encapsulated vaccine samples were stored at 4°C, 25°C, 37°C, and 45°C under different packaging conditions. The results showed that the encapsulated vaccine maintained its hemagglutination potency, antigenic property and virus particle morphology over extended periods of time while the unprocessed vaccine suspended in solution lost virtually all hemagglutination activities and morphology within a few days. According to the results, we concluded that solid-state encapsulation of the vaccine in dissolving microneedles provided more potent stability over liquid-state vaccine.
520 $a Finally, based on all the optimizations of dissolving microneedles described in previous chapters, arrowhead microneedles encapsulating inactivated influenza virus vaccine were evaluated in vivo. Mice were immunized with a single dose using arrowhead microneedles. The results showed that the immune responses as measured by virus-specific IgG levels 4 weeks after vaccination were statistically equivalent to the intramuscular injection of the same vaccine dose using hypodermic needles. The immunized mice were protected from lethal virus challenge.
520 $a We envision the newly developed dissolving microneedle system can be a safe, patient compliant, easy-to-use and self-administered method for rapid drug and vaccine delivery to the skin.
590 $a School code: 0078.
650 4 $a Engineering, Biomedical. $3 1017684
650 4 $a Health Sciences, Pharmacy. $3 1017737
650 4 $a Health Sciences, Immunology. $3 1017716
690 $a 0541
690 $a 0572
690 $a 0982
710 2 $a Georgia Institute of Technology. $3 696730
773 0 $t Dissertation Abstracts International $g 72-06B.
790 1 0 $a Prausnitz, Mark, $e advisor
790 $a 0078
791 $a Ph.D.
792 $a 2009
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