Pharmaceutical nanocarrier association with chondrocytes and cartilage explants: influence of surface modification and extracellular matrix depletion.
Osteoarthritis Cartilage
; 21(2): 377-84, 2013 Feb.
Article
en En
| MEDLINE
| ID: mdl-23186944
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.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Cartílago Articular
/
Membrana Celular
/
Condrocitos
/
Matriz Extracelular
/
Péptidos de Penetración Celular
/
Liposomas
/
Micelas
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Límite:
Animals
Idioma:
En
Revista:
Osteoarthritis Cartilage
Asunto de la revista:
ORTOPEDIA
/
REUMATOLOGIA
Año:
2013
Tipo del documento:
Article
País de afiliación:
Estados Unidos