PhD Defense by Lina María Mancipe Castro

Event Details
  • Date/Time:
    • Tuesday July 7, 2020
      12:00 pm - 2:00 pm
  • Location: REMOTE
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  • URL: REMOTE
  • Email:
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Summaries

Summary Sentence: Articular cartilage- and synoviocyte-binding small molecule drug delivery system for the intra-articular treatment of osteoarthritis

Full Summary: No summary paragraph submitted.

Lina María Mancipe Castro

BioE PhD Defense

July 7, 2020 12pm

https://bluejeans.com/651279321

 

 

 

Advisor: Andrés J. García, PhD, (Georgia Institute of Technology)

Co-advisor: Robert E. Guldberg, PhD (University of Oregon)

 

Committee:

Nick Willett, PhD; (Emory Department of Orthopedics)

SusanThomas, PhD; (Georgia Institute of Technology)

James Dahlman, PhD. (Georgia Institute of Technology)

 

Articular cartilage- and synoviocyte-binding small molecule drug delivery system for the intra-articular treatment of osteoarthritis

 

Intra-articular (IA) injection is an attractive route of administration for the treatment of osteoarthritis (OA). However, free drugs injected into the joint space are subjected to clearance mechanisms, which reduce their IA retention time. Additionally, several drug candidates can induce adverse off-target effects on different IA tissues. To overcome these limitations, tissue-binding, nano-composite microgels as IA small molecule drug delivery vehicles were designed. Micron-scale poly(ethylene glycol) (PEG) hydrogels, presenting  cartilage- or synoviocyte-binding peptides and containing small molecule-loaded poly(lactic-co-glycolic) acid (PLGA) nanoparticles (NPs) were synthesized using microfluidics technology. Microgels loaded with a model small molecule (rhodamine B) exhibited a sustained, near-zero order release over 16 days. Additionally, PEG microgels functionalized with synoviocyte- or cartilage-targeting peptides, presented specific binding to rabbit and human synoviocytes, and to bovine articular cartilage in vitro, respectively. Using a rat model of knee OA, microgels were shown to be retained in the IA space for at least 3 weeks and did not induce detectable joint degenerative changes as measured by EPIC-μCT and histology. Finally, histological analysis demonstrated that synoviocyte-binding microgels were found trapped within the synovial membrane and significantly increased the IA retention time of a model small molecule near infra-red dye in vivo. Overall, these results suggest that nano-composite PEG microgels presenting tissue-binding peptides could be a promising strategy to achieve tissue-localized drug delivery and prolonged IA retention of small molecule drugs for OA treatment.

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Graduate Studies

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Keywords
Phd Defense
Status
  • Created By: Tatianna Richardson
  • Workflow Status: Published
  • Created On: Jun 24, 2020 - 1:37pm
  • Last Updated: Jun 24, 2020 - 1:37pm