Maryam Ali

Auburn University, Auburn, Alabama, United States

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Publications (4)13.31 Total impact

  • Maryam Ali · Mark E Byrne
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    ABSTRACT: Current dry eye treatment includes delivering comfort agents to the eye via drops, but low bioavailability and multiple administration continues to be a barrier to effective treatment. There exists a significant unmet need for devices to treat dry eye and for more comfortable contact lenses. Using molecular imprinting strategies with an analysis of biology, we have rationally designed and synthesized hydrogel contact lenses that can release hyaluronic acid (HA) at a controlled rate. Delayed release characteristics were significantly improved through biomimetic imprinting, as multiple functional monomers provided non-covalent complexation points within nelfilcon A gels without altering structural, mechanical, or optical properties. The diffusion coefficient of 1.2 million Dalton HA was controlled by varying the number and variety of functional monomers (increasing the variety lowered the HA diffusion coefficient 1.5 times more than single functional monomers, and 1.6 times more than nelfilcon A alone). HA can be delivered from a daily disposable lens at a therapeutic rate of approximately 6 microg/h for 24 h. This is the first demonstration of imprinting a large molecular weight polymer within a hydrogel and the effect of imprinting on the reptation of the long chain macromolecule from the structure.
    Pharmaceutical Research 02/2009; 26(3):714-26. DOI:10.1007/s11095-008-9818-6 · 3.42 Impact Factor
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    ABSTRACT: Molecular imprinting provides a rational design strategy for the development of controlled release drug delivery systems. We demonstrate that imprinting a network results in macromolecular memory for the template molecule, indicated by the two or more times greater partitioning into these networks as compared to non-imprinted networks. Partitioning of drug into networks synthesized from multiple functional monomers was 8 times greater than networks synthesized from single monomers. One-dimensional permeation studies showed that the gel with maximum incorporated chemical functionality had the lowest diffusion coefficient, which was at least an order of magnitude lower than all other gels studied. All imprinted networks had significantly lower diffusion coefficients than non-imprinted networks, in spite of comparable mesh sizes and equilibrium polymer volume fractions in the swollen state. This work also demonstrates molecular imprinting using a "living/controlled" polymerization strategy to enhance template loading/affinity and delay release in weakly crosslinked gels. Recognition studies revealed more than a 50% increase in template loading and dynamic template release studies showed that imprinting via "living" polymerization extends or delays the template release profile by two-fold over that of imprinting via conventional free-radical polymerization techniques and four-fold over the control network. The imprinted gel and imprinted gel prepared via "living/controlled" polymerization release profiles were less Fickian and moved toward zero-order release with profile coefficients of 0.68 and 0.70, respectively.
    Conference proceedings: ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference 01/2009; 2009:242-5. DOI:10.1109/IEMBS.2009.5332862
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    ABSTRACT: 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 x 10(-9) to 5.57 x 10(-10) cm(2)/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 (r(2)=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.
    Journal of Controlled Release 01/2008; 124(3):154-62. DOI:10.1016/j.jconrel.2007.09.006 · 7.71 Impact Factor
  • Maryam Ali · Mark Edward Byrne
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    ABSTRACT: Vision significantly affects quality of life and the treatment of ocular disease poses a number of unique challenges. This review presents the major challenges faced during topical ocular drug administration and highlights strategies used to overcome the natural transport barriers of the eye. The circulation of tear fluid and aqueous humor decrease the residence time of topically delivered drugs, while ocular barriers in the corneal and conjuctival epithelia and the retinal pigment epithelium limit transport. Successful treatment strategies increase the residence time of drugs in the eye and/or enhance the ability of the drug to penetrate the ocular barriers and reach the target tissue. In this review, we discuss several drug-delivery strategies that have achieved clinical success or demonstrate high potential. We also draw attention to a number of excellent reviews that explore various ocular drug-delivery techniques in depth. Finally, we highlight cutting-edge drug-delivery technologies that improve the efficacy of current drug-delivery methods or use proven techniques to deliver novel therapeutics.
    Expert Review of Clinical Pharmacology 01/2008; 1(1):145-61. DOI:10.1586/17512433.1.1.145 · 2.18 Impact Factor