TY - JOUR
T1 - Zero-order therapeutic release from imprinted hydrogel contact lenses within in vitro physiological ocular tear flow
AU - Ali, Maryam
AU - Horikawa, Shin
AU - Venkatesh, Siddarth
AU - Saha, Jishnu
AU - Hong, Jong Wook
AU - Byrne, Mark E.
N1 - Funding Information:
These investigations were supported by an ORAU Ralph E. Powe Junior Faculty Enhancement Award (MEB), an Auburn University Biogrant, and a Grant-In-Aid of Research from the National Academy of Sciences, administered by Sigma Xi (SV). We thank Brock Wilson for aiding in the microfluidic device characterization.
PY - 2007/12/20
Y1 - 2007/12/20
N2 - Zero-order or concentration independent release kinetics are highly desirable from drug delivery devices. In this paper we demonstrate experimentally, for the first time, zero-order release of a small molecular weight therapeutic, ketotifen fumarate (MW = 425), from molecularly imprinted hydrogels used as therapeutic contact lenses. We performed dynamic, in vitro drug release studies from imprinted hydrogel contact lenses within a novel microfluidic device that simulates the volumetric flow rates, tear volume and tear composition of the eye. Imprinted gels with multiple functional monomers and complexation points to the drug demonstrated a significantly delayed release of drug compared to less functionalized systems. There were no statistical differences in experimentally determined equilibrium swollen polymer volume fractions, which correlate with molecular weight between crosslinks and mesh size of the gel. Under infinite sink conditions, imprinted contact lenses demonstrated Fickian (concentration dependent) release kinetics with diffusion coefficients ranging from 4.04 × 10- 9 to 5.57 × 10- 10 cm2/s. The highest functionalized gel exhibited a diffusion coefficient averaging ten times smaller than less functionalized gels and released drug for over 5 days with 3 distinct rates of release. Under physiological volumetric flow rates, the release rate was constant for a duration of 3.5 days delivering a therapeutically relevant dosage and was fit to a power law model indicating zero-order release characteristics with n = 0.981 ± 0.006 (r2 = 0.997). This work demonstrates the potential of micro/nanofluidic devices to determine physiological release rates and stresses the importance of matching local conditions to adequately characterize drug delivery devices. It also demonstrates the enormous potential for molecular imprinting to further tailor therapeutic release kinetics via the imprinting process.
AB - Zero-order or concentration independent release kinetics are highly desirable from drug delivery devices. In this paper we demonstrate experimentally, for the first time, zero-order release of a small molecular weight therapeutic, ketotifen fumarate (MW = 425), from molecularly imprinted hydrogels used as therapeutic contact lenses. We performed dynamic, in vitro drug release studies from imprinted hydrogel contact lenses within a novel microfluidic device that simulates the volumetric flow rates, tear volume and tear composition of the eye. Imprinted gels with multiple functional monomers and complexation points to the drug demonstrated a significantly delayed release of drug compared to less functionalized systems. There were no statistical differences in experimentally determined equilibrium swollen polymer volume fractions, which correlate with molecular weight between crosslinks and mesh size of the gel. Under infinite sink conditions, imprinted contact lenses demonstrated Fickian (concentration dependent) release kinetics with diffusion coefficients ranging from 4.04 × 10- 9 to 5.57 × 10- 10 cm2/s. The highest functionalized gel exhibited a diffusion coefficient averaging ten times smaller than less functionalized gels and released drug for over 5 days with 3 distinct rates of release. Under physiological volumetric flow rates, the release rate was constant for a duration of 3.5 days delivering a therapeutically relevant dosage and was fit to a power law model indicating zero-order release characteristics with n = 0.981 ± 0.006 (r2 = 0.997). This work demonstrates the potential of micro/nanofluidic devices to determine physiological release rates and stresses the importance of matching local conditions to adequately characterize drug delivery devices. It also demonstrates the enormous potential for molecular imprinting to further tailor therapeutic release kinetics via the imprinting process.
KW - Biomimetic
KW - Controlled release
KW - Drug delivery
KW - Microfluidics
KW - Molecular imprinting
UR - http://www.scopus.com/inward/record.url?scp=36148962885&partnerID=8YFLogxK
U2 - 10.1016/j.jconrel.2007.09.006
DO - 10.1016/j.jconrel.2007.09.006
M3 - Article
C2 - 17964678
AN - SCOPUS:36148962885
SN - 0168-3659
VL - 124
SP - 154
EP - 162
JO - Journal of Controlled Release
JF - Journal of Controlled Release
IS - 3
ER -