TY - JOUR
T1 - Development and characterization of a novel drug nanocarrier for oral delivery, based on self-assembled β-casein micelles
AU - Bachar, Michal
AU - Mandelbaum, Amitai
AU - Portnaya, Irina
AU - Perlstein, Hadas
AU - Even-Chen, Simcha
AU - Barenholz, Yechezkel
AU - Danino, Dganit
N1 - Funding Information:
The work was partially supported by the RBNI at the Technion , and the Barenholz Fund at HUJI . I.P. acknowledges the support of a joint grant from the Center for Absorption in Science of the Ministry of Immigrant Absorption and the Committee for Planning and Budgeting of the Council for Higher Education under the framework of the KAMEA program. We greatly appreciate the assistance of Adi Chalilov and Tanya Turovsky in preparing solutions for the quantitative encapsulation analysis.
PY - 2012/6/10
Y1 - 2012/6/10
N2 - β-casein is an amphiphilic protein that self-organizes into well-defined core-shell micelles. We developed these micelles as efficient nanocarriers for oral drug delivery. Our model drug is celecoxib, an anti-inflammatory hydrophobic drug utilized for treatment of rheumatoid arthritis and osteoarthritis, now also evaluated as a potent anticancer drug. This system is unique as it enables encapsulation loads > 100-fold higher than other β-casein/drug formulations, and does not require additives as do other formulations that have high loadings. This is combined with the ability to lyophilize the formulation without a cryoprotectant, long-term physical and chemical stability of the resulting powder, and fully reversible reconstitution of the structures by rehydration. The dry dosage form, in which > 95% of the drug is encapsulated, meets the daily dose. Cryo-TEM and DLS prove that drug encapsulation results in micelle swelling, and X-ray diffraction shows that the encapsulated drug is amorphous. Altogether, our novel dosage form is highly advantageous for oral administration.
AB - β-casein is an amphiphilic protein that self-organizes into well-defined core-shell micelles. We developed these micelles as efficient nanocarriers for oral drug delivery. Our model drug is celecoxib, an anti-inflammatory hydrophobic drug utilized for treatment of rheumatoid arthritis and osteoarthritis, now also evaluated as a potent anticancer drug. This system is unique as it enables encapsulation loads > 100-fold higher than other β-casein/drug formulations, and does not require additives as do other formulations that have high loadings. This is combined with the ability to lyophilize the formulation without a cryoprotectant, long-term physical and chemical stability of the resulting powder, and fully reversible reconstitution of the structures by rehydration. The dry dosage form, in which > 95% of the drug is encapsulated, meets the daily dose. Cryo-TEM and DLS prove that drug encapsulation results in micelle swelling, and X-ray diffraction shows that the encapsulated drug is amorphous. Altogether, our novel dosage form is highly advantageous for oral administration.
KW - Amphiphilic block copolymers
KW - Celecoxib
KW - Drug delivery
KW - Nanomedicine
KW - Protein micelles
UR - http://www.scopus.com/inward/record.url?scp=84861702785&partnerID=8YFLogxK
U2 - 10.1016/j.jconrel.2012.01.004
DO - 10.1016/j.jconrel.2012.01.004
M3 - 文章
C2 - 22266050
AN - SCOPUS:84861702785
SN - 0168-3659
VL - 160
SP - 164
EP - 171
JO - Journal of Controlled Release
JF - Journal of Controlled Release
IS - 2
ER -