Green fluorescent proteins engineered for cartilage-targeted drug delivery: Insights for transport into highly charged avascular tissues

Biomaterials
Y KrishnanA J Grodzinsky

Abstract

Osteoarthritis (OA), the most common form of arthritis, is a multi-factorial disease that primarily affects cartilage as well as other joint tissues such as subchondral bone. The lack of effective drug delivery, due to the avascular nature of cartilage and the rapid clearance of intra-articularly delivered drugs via the synovium, remains a major challenge in the development of disease modifying drugs for OA. Cationic delivery carriers can significantly enhance the uptake, penetration and retention of drugs in cartilage by interacting with negatively charged matrix proteoglycans. In this study, we used "supercharged" green fluorescent proteins (GFPs), engineered to have a wide range of net positive charge and surface charge distributions, to characterize the effects of carrier charge on transport into cartilage in isolation of other factors such as carrier size and shape. We quantified the uptake, extent of cartilage penetration and cellular uptake of the GFP variants into living human knee cartilage and bovine cartilage explants. Based on these results, we identified optimal net charges of GFP carriers for potential drug targets located within cartilage extracellular matrix as well as the resident live chondrocytes. These catio...Continue Reading

References

Oct 1, 1988·Analytical Biochemistry·Y J KimA J Grodzinsky
May 1, 1970·Biophysical Journal·A Maroudas
Jan 1, 1997·Osteoarthritis and Cartilage·C MuehlemanK E Kuettner
May 27, 1999·Annals of the Rheumatic Diseases·D E Shepherd, B B Seedhom
May 6, 2006·The Journal of Chemical Physics·Zhaoyang Ou, M Muthukumar
Nov 16, 2006·Journal of Orthopaedic Trauma·Thomas D BrownJoseph A Buckwalter
May 18, 2007·Osteoarthritis and Cartilage·V B KrausG McDaniel
Aug 2, 2007·Journal of the American Chemical Society·Michael S LawrenceDavid R Liu
Feb 29, 2008·Journal of Pharmaceutical Sciences·Claus LarsenPia H Andersen
Apr 7, 2009·Bioinformatics·Stephan PreibischPavel Tomancak
Apr 27, 2011·Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society·Donald D AndersonJoseph A Buckwalter
Jun 21, 2011·Lancet·Johannes W J BijlsmaFloris P J G Lafeber
Jul 31, 2012·Chemistry & Biology·David B ThompsonDavid R Liu
Nov 13, 2012·International Journal of Nanomedicine·Eleonore Fröhlich
Nov 6, 2013·Nature Reviews. Rheumatology·Christopher H EvansLori A Setton
Feb 5, 2014·Biomacromolecules·Fredrick P RojasLin Han
Apr 23, 2014·Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society·Ambika G BajpayeeRyan M Porter
Jan 30, 2015·Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society·Ambika G BajpayeeRyan M Porter
Feb 17, 2017·Nature Reviews. Rheumatology·Ambika G Bajpayee, Alan J Grodzinsky
Nov 28, 2017·Arthritis & Rheumatology·S Reza Jafarzadeh, David T Felson
Apr 18, 2018·The Journal of Bone and Joint Surgery. American Volume·Philip G ConaghanUNKNOWN FX006-2014-008 Participating Investigators

❮ Previous
Next ❯

Citations

Jun 9, 2019·Journal of Biomechanical Engineering·Olufunmilayo AdebayoMarjolein C H van der Meulen
Oct 8, 2019·Chemical Science·Wenjin XiaoAdam W Perriman
Aug 18, 2020·Bioelectricity·Cameron C YoungAmbika G Bajpayee
Sep 3, 2020·Polymers·Jose Rodrigo MaganaIlja K Voets
Nov 25, 2020·Current Opinion in Rheumatology·Shikhar MehtaAmbika G Bajpayee
Dec 18, 2019·Journal of Controlled Release : Official Journal of the Controlled Release Society·Tengfei HeAmbika G Bajpayee
Feb 18, 2021·Journal of Colloid and Interface Science·Qi HanTamar L Greaves
Jun 19, 2019·Journal of Biomechanical Engineering·Olufunmilayo O AdebayoMarjolein C H van der Meulen
Mar 13, 2021·Advanced Therapeutics·Carlisle R DeJuliusCraig L Duvall
Jul 30, 2021·Osteoarthritis and Cartilage Open·Rebecca Mae BlackPatrik Önnerfjord
Jan 16, 2021·ACS Biomaterials Science & Engineering·Lucy Ngo, Melissa L Knothe Tate
Nov 30, 2018·Science Translational Medicine·Christopher H Evans
Dec 3, 2021·Biomacromolecules·Justin M Horn, Allie C Obermeyer
Dec 25, 2021·Biophysical Journal·Tahoura SamadKatharina Ribbeck

❮ Previous
Next ❯

Related Concepts

Related Feeds

Adult Stem Cells

Adult stem cells reside in unique niches that provide vital cues for their survival, self-renewal, and differentiation. They hold great promise for use in tissue repair and regeneration as a novel therapeutic strategies. Here is the latest research.

Anti-inflammatory Treatments

A drug or substance that reduces inflammation (redness, swelling, and pain) in the body. Anti-inflammatory agents block certain substances in the body that cause inflammation and swelling. Discover the latest research on anti-inflammatory treatments here