Development and characterization of a novel drug nanocarrier for oral delivery, based on self-assembled β-casein micelles

Michal Bachar; Amitai Mandelbaum; Irina Portnaya; Hadas Perlstein; Simcha Even-Chen; Yechezkel Barenholz; Dganit Danino

doi:10.1016/j.jconrel.2012.01.004

Development and characterization of a novel drug nanocarrier for oral delivery, based on self-assembled β-casein micelles

Michal Bachar, Amitai Mandelbaum, Irina Portnaya, Hadas Perlstein, Simcha Even-Chen, Yechezkel Barenholz, Dganit Danino^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

137 Scopus citations

Abstract

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.

Original language	English
Pages (from-to)	164-171
Number of pages	8
Journal	Journal of Controlled Release
Volume	160
Issue number	2
DOIs	https://doi.org/10.1016/j.jconrel.2012.01.004
State	Published - 10 Jun 2012
Externally published	Yes

Keywords

Amphiphilic block copolymers
Celecoxib
Drug delivery
Nanomedicine
Protein micelles

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10.1016/j.jconrel.2012.01.004

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title = "Development and characterization of a novel drug nanocarrier for oral delivery, based on self-assembled β-casein micelles",

abstract = "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.",

keywords = "Amphiphilic block copolymers, Celecoxib, Drug delivery, Nanomedicine, Protein micelles",

author = "Michal Bachar and Amitai Mandelbaum and Irina Portnaya and Hadas Perlstein and Simcha Even-Chen and Yechezkel Barenholz and Dganit Danino",

note = "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.",

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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.

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KW - Celecoxib

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KW - Nanomedicine

KW - Protein micelles

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Development and characterization of a novel drug nanocarrier for oral delivery, based on self-assembled β-casein micelles

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