Modulation of vincristine and doxorubicin binding and release from silk films.
Sustained release drug delivery systems remain a major clinical need for small molecule therapeutics in oncology. Here, mechanisms of small molecule interactions with silk protein films were studied with cationic oncology drugs, vincristine and doxorubicin, with a focus on hydrophobicity (non-ionic surfactant) and charge (pH and ionic strength). Interactions were primarily driven by charge interactions between the positively charged drugs and the negatively charged groups within the silk films. Exploiting chemical modifications of silk further modulated the drug interactions in a controlled fashion. Increasing anionic side groups via carboxylate- and sulfonate-modifications of tyrosine side chains in the silk protein using diazonium coupling chemistry, increased drug binding and altered drug release. The effects of silk film protein crystallinity, beta sheet content, on drug binding and release were also explored. Lower crystallinity supported more rapid drug binding when compared to higher crystalline silk films. The drug release kinetics were governed by the protonation state of vincristine and doxorubicin and were tunable based on silk crystallinity and chemistry. These studies depict an approach to characterize small molecule-silk protein interactions and methods to tune drug binding and release kinetics from this protein delivery matrix.
Department of Biomedical Engineering, Tufts University, Medford, MA, USA.
Jeannine M
JM
Coburn
Department of Biochemistry, Tufts University, Medford, MA, USA.
Elim
E
Na
Department of Biomedical Engineering, Tufts University, Medford, MA, USA. Electronic address: david.kaplan@tufts.edu.
David L
DL
Kaplan
D000903:Antibiotics, Antineoplastic / Q000737:chemistry / Q000378:metabolism*; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000378:metabolism*; D003460:Crystallization; D003692:Delayed-Action Preparations; D004317:Doxorubicin / Q000737:chemistry / Q000378:metabolism*; D004337:Drug Carriers; D004339:Drug Compounding; D005349:Fibroins / Q000737:chemistry / Q000378:metabolism*; D007700:Kinetics; D015394:Molecular Structure; D011485:Protein Binding; D012995:Solubility; D013329:Structure-Activity Relationship; D013499:Surface Properties; D013678:Technology, Pharmaceutical / Q000379:methods; D014750:Vincristine / Q000737:chemistry / Q000378:metabolism*
D000903:Antibiotics, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D014750:Vincristine; D004317:Doxorubicin; D005349:Fibroins
Biomaterials; Cancer; Controlled release; Doxorubicin; Silk fibroin; Vincristine