Literature DB >> 23186944

Pharmaceutical nanocarrier association with chondrocytes and cartilage explants: influence of surface modification and extracellular matrix depletion.

K A Elsaid1, L Ferreira, T Truong, A Liang, J Machan, G G D'Souza.   

Abstract

OBJECTIVE: To evaluate cartilage diffusion and isolated chondrocyte association of micelles and liposomes and to determine the effect of cell-penetrating peptide (CPP) surface functionalization and extracellular matrix depletion on chondrocyte association and cartilage diffusion, respectively.
METHODS: Rhodamine-labeled micelles and liposomes were incubated with bovine chondrocytes and cell-associated fluorescence was quantified using flow cytometry. Rhodamine-labeled CPP-modified micelles and liposomes were incubated with chondrocytes and cell-associated fluorescence was compared to unmodified nanocarriers. Rhodamine-labeled micelles and liposomes were incubated with bovine cartilage explants for 1, 2 and 4 h and cartilage-associated fluorescence was compared across groups. Cartilage explants were treated with interleukin-1 alpha (IL-1α) or with 0.25% trypsin. Rhodamine-labeled micelles and liposomes were incubated with control, IL-1 and trypsin-treated explants and cartilage-associated fluorescence was compared across groups.
RESULTS: Chondrocyte-associated fluorescence following treatment with micelles was significantly higher (P < 0.001) than fluorescence in the cells treated with liposomes while there was no difference between cell-associated fluorescence in the liposomes-treated and untreated controls. CPP-modified nanocarriers exhibited a significant increase in chondrocyte association compared to unmodified nanocarriers (P < 0.001). Micelles exhibited a time and concentration-dependent diffusion in cartilage explants while liposomes showed no diffusion. Following IL-1 and trypsin treatments, micelle diffusion in articular cartilage was significantly higher (P < 0.001) than their diffusion in untreated explants.
CONCLUSION: Micelles exhibit superior association with isolated chondrocytes compared to liposomes. Surface modification with a CPP enhances chondrocyte association of both nanocarriers. 15 nm diameter micelles are better than 138 nm diameter liposomes in penetrating articular cartilage and extracellular matrix depletion enhances micelle penetration.
Copyright © 2012 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

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Year:  2012        PMID: 23186944      PMCID: PMC3556184          DOI: 10.1016/j.joca.2012.11.011

Source DB:  PubMed          Journal:  Osteoarthritis Cartilage        ISSN: 1063-4584            Impact factor:   6.576


  33 in total

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