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Investigation of Poly(Acrylic Acid) Microgels for the Treatment of Osteoarthritis: Cartilage Lubrication, Sustained Drug Delivery, and Prolonged Residence Time /

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Investigation of Poly(Acrylic Acid) Microgels for the Treatment of Osteoarthritis: Cartilage Lubrication, Sustained Drug Delivery, and Prolonged Residence Time // Ruben J Trujillo.
作者:	Trujillo, Ruben J.,
面頁冊數:	1 electronic resource (227 pages)
附註:	Source: Dissertations Abstracts International, Volume: 86-12, Section: B.
Contained By:	Dissertations Abstracts International86-12B.
標題:	Biomedical engineering. -
電子資源:	https://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=31838898
ISBN:	9798283138305

Investigation of Poly(Acrylic Acid) Microgels for the Treatment of Osteoarthritis: Cartilage Lubrication, Sustained Drug Delivery, and Prolonged Residence Time /
Trujillo, Ruben J.,

Investigation of Poly(Acrylic Acid) Microgels for the Treatment of Osteoarthritis: Cartilage Lubrication, Sustained Drug Delivery, and Prolonged Residence Time /Ruben J Trujillo. - 1 electronic resource (227 pages)

Source: Dissertations Abstracts International, Volume: 86-12, Section: B.

Osteoarthritis (OA) is a debilitating joint disease, impacting over 650 million people worldwide and is the leading cause of disability in the United States. The most commonly affected joints are the knees and hips, with risk factors include weight, age, and injury. Current treatment options temporarily mitigate pain, but long-term relief is difficult to achieve. Within the joint space as OA progresses, there are changes in cartilage integrity, increased inflammation, and changes in native synovial fluid composition. Intra-articular clearance rate is increased due to inflammation of the synovial lining, and lubrication of the articular joint space is hindered due to synovial fluid and cartilage changes. With an increase in clearance rate, molecules less than 10 MDa have an approximate half-life of less than 12 hours. Localized intra-articular therapies have been investigated for decades to treat OA, but their efficacy is debated, they generally require multiple repeat injections, and increased clearance rate decreases their intra-articular residence time. With the multiple complexities associated with OA, there is a need for a treatment that efficiently addresses the main pathological hurdles: restore lubrication to articular cartilage, sustained delivery of a disease modifying therapeutic, and long-term residence time within the joint space.In this dissertation, I first explore the synthesis and characterization of a micron-sized hydrogel (microgel) library for the lubrication of articular cartilage (Chapter 2). The microgel library allows for the examination of 9 distinct microgel formulations, varying crosslinking density and polymer molecular weight. Interestingly, microgel formulations exhibit low measured viscosity values, but achieve lubrication equivalent to solutions that are 10,000 times as viscous. Ultimately, crosslinking density was determined to be the largest driver of lubrication, with low crosslinking density formulations lubricating similar to native synovial fluid.Interleukin-1 receptor antagonist (IL-1Ra) was identified as a relevant therapeutic protein for the treatment OA, as it inhibits the binding of IL-1, a key inflammatory cytokine associated with OA progression. The controlled delivery of IL-1Ra from microgel formulations was investigated via two unique approaches: 1) Treatment of protein-loaded microgels with CaCl2 to prevent burst release via ionic crosslinks. 2) Conjugation of activated carboxyl groups with small molecules to study the effects of negative, positive, polar, and non-polar side chains on uptake and release of IL-1Ra from small molecule modified microgels (Chapter 3). This work revealed that microgel modifications altered total IL-1Ra uptake, improving uptake by 1.7 times compared to unmodified microgels. Additionally, modified microgel formulations achieved sustained release of IL-1Ra for greater than 60 days, whereas unmodified microgels exhibited 100% burst release of IL-1Ra within 6 hours. Finally, the half-life of microgels was investigated via intra-articular injections in healthy Sprague-Dawley rats (Chapter 3). Microgels demonstrated a prolonged in vivo residence time, with a calculated β half-life of 93 days.Overall, this dissertation highlights the use of poly(acrylic acid) microgels as competitive biolubricants and drug delivery vehicles for OA treatment. Lubrication of articular cartilage using low viscosity microgel suspensions informs the design of next generation intra-articular therapies for OA treatment. With the use of novel post-synthesis modifications to tune the delivery of IL-1Ra, these techniques lay the foundation for future drug delivery studies using hydrogel systems.

English

ISBN: 9798283138305Subjects--Topical Terms:

535387
Biomedical engineering.
Subjects--Index Terms:

Drug delivery

Investigation of Poly(Acrylic Acid) Microgels for the Treatment of Osteoarthritis: Cartilage Lubrication, Sustained Drug Delivery, and Prolonged Residence Time /
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