Silk fibroin as an organic polymer for controlled drug delivery.
The pharmaceutical utility of silk fibroin (SF) materials for drug delivery was investigated. SF films were prepared from aqueous solutions of the fibroin protein polymer and crystallinity was induced and controlled by methanol treatment. Dextrans of different molecular weights, as well as proteins, were physically entrapped into the drug delivery device during processing into films. Drug release kinetics were evaluated as a function of dextran molecular weight, and film crystallinity. Treatment with methanol resulted in an increase in beta-sheet structure, an increase in crystallinity and an increase in film surface hydrophobicity determined by FTIR, X-ray and contact angle techniques, respectively. The increase in crystallinity resulted in the sustained release of dextrans of molecular weights ranging from 4 to 40 kDa, whereas for less crystalline films sustained release was confined to the 40 kDa dextran. Protein release from the films was studied with horseradish peroxidase (HRP) and lysozyme (Lys) as model compounds. Enzyme release from the less crystalline films resulted in a biphasic release pattern, characterized by an initial release within the first 36 h, followed by a lag phase and continuous release between days 3 and 11. No initial burst was observed for films with higher crystallinity and subsequent release patterns followed linear kinetics for HRP, or no substantial release for Lys. In conclusion, SF is an interesting polymer for drug delivery of polysaccharides and bioactive proteins due to the controllable level of crystallinity and the ability to process the biomaterial in biocompatible fashion under ambient conditions to avoid damage to labile compounds to be delivered.
Hofmann
S
S
Drug Formulation and Delivery, ETH Zurich, 8093 Zurich, Switzerland.
Foo
C T Wong Po
CT
Rossetti
F
F
Textor
M
M
Vunjak-Novakovic
G
G
Kaplan
D L
DL
Merkle
H P
HP
Meinel
L
L
D000327:Adsorption; D000818:Animals; D012831:Bombyx / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D003460:Crystallization; D003692:Delayed-Action Preparations / Q000737:chemistry* / Q000493:pharmacokinetics; D003911:Dextrans / Q000737:chemistry / Q000493:pharmacokinetics; D005349:Fibroins / Q000737:chemistry* / Q000302:isolation & purification; D005453:Fluorescence; D006735:Horseradish Peroxidase / Q000737:chemistry / Q000493:pharmacokinetics; D000432:Methanol / Q000737:chemistry; D018625:Microscopy, Atomic Force; D008970:Molecular Weight; D009113:Muramidase / Q000737:chemistry / Q000493:pharmacokinetics; D011108:Polymers / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared; D013499:Surface Properties; D013678:Technology, Pharmaceutical / Q000379:methods; D013997:Time Factors
D003692:Delayed-Action Preparations; D003911:Dextrans; D011108:Polymers; D005349:Fibroins; D006735:Horseradish Peroxidase; D009113:Muramidase; D000432:Methanol