A. James Clark School of Engineering

Permanent URI for this communityhttp://hdl.handle.net/1903/1654

The collections in this community comprise faculty research works, as well as graduate theses and dissertations.

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Subject: search.filters.subject.controlled release

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    Effect of a Cationic Surfactant on Microemulsion Globules and Drug Release from Hydrogel Contact Lenses
    (MDPI, 2019-06-06) Torres-Luna, Cesar; Hu, Naiping; Koolivand, Abdollah; Fan, Xin; Zhu, Yuli; Domszy, Roman; Yang, Jeff; Yang, Arthur; Wang, Nam Sun
    The present study evaluates the in vitro release of diclofenac sodium (DFNa) from contact lenses based on poly-2-hydroxyethyl methacrylate (pHEMA) hydrogels containing an embedded microemulsion to extend release duration. The oil (ethyl butyrate)-in-water microemulsion systems are prepared with two non-ionic surfactants, Brij 97 or Tween 80, together with a long-alkyl chain cationic surfactant, cetalkonium chloride (CKC). Without CKC, Brij 97 or Tween 80-based microemulsions showed average droplet sizes of 12 nm and 18 nm, respectively. The addition of CKC decreased the average droplet sizes to 2–5 nm for both non-ionic surfactants. Such significant reduction in the average droplet size corresponds to an increase in the DFNa release duration as revealed by the in vitro experiments. Contact lens characterization showed that important properties such as optical transparency and water content of Brij 97-based contact lenses with cationic microemulsions was excellent. However, the optical transparency of the corresponding Tween 80 based contact lenses was unsatisfactory. The results indicate that cationic microemulsion-laden contact lenses can benefit from combinatory effects of microemulsions and cationic surfactant at low CKC weight percentage, e.g., with the release of 70% of the drug in 45, 10, and 7 h for B97-CKC-0.45%, CKC-0.45%, and control lenses, respectively. However, the microemulsion effect on extending DFNa release became negligible at the highest CKC weight percentage (1.8%).
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    Formation of Drug-Participating Catanionic Aggregates for Extended Delivery of Non-Steroidal Anti-Inflammatory Drugs from Contact Lenses
    (MDPI, 2019-10-10) Torres-Luna, Cesar; Koolivand, Abdollah; Fan, Xin; Agrawal, Niti R.; Hu, Naiping; Zhu, Yuli; Domszy, Roman; Briber, Robert M.; Wang, Nam Sun; Yang, Arthur
    This paper focuses on extending drug release duration from contact lenses by incorporating catanionic aggregates. The aggregates consist of a long-chain cationic surfactant, i.e., cetalkonium chloride (CKC), and an oppositely charged anti-inflammatory amphiphilic drug. We studied three non-steroidal anti-inflammatory (NSAID) drugs with different octanol–water partition coefficients; diclofenac sodium (DFNa), flurbiprofen sodium (FBNa), and naproxen sodium (NPNa). Confirmation of catanionic aggregate formation in solution was determined by steady and dynamic shear rheology measurements. We observed the increased viscosity, shear thinning, and viscoelastic behavior characteristic of wormlike micelles; the rheological data are reasonably well described using a Maxwellian fluid model with a single relaxation time. In vitro release experiments demonstrated that the extension in the drug release time is dependent on the ability of a drug to form viscoelastic catanionic aggregates. Such aggregates retard the diffusive transport of drug molecules from the contact lenses. Our study revealed that the release kinetics depends on the CKC concentration and the alkyl chain length of the cationic surfactant. We demonstrated that more hydrophobic drugs such as diclofenac sodium show a more extended release than less hydrophobic drugs such as naproxen sodium.
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    Therapeutic contact lenses for extended drug delivery
    (2021) Torres Luna, Cesar Eduardo; Wang, Nam Sun; Briber, Robert M; Chemical Engineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)
    There is significant interest in hydrogel-based drug-eluting contact lenses as platforms for topical ocular drug delivery. These devices have shown to provide an increased residence time of drugs at the surface of the eye, leading to enhanced bioavailability (~ 50%) when compared to eye drops (1–5%). One major limitation of contact lenses for drug delivery is that most drugs are released in a few hours, which limits their application for extended delivery. In this dissertation, we develop novel drug-eluting contact lenses that are capable of achieving extended in vitro drug delivery. In our first study, we describe the application of drug-participating catanionic aggregates in poly-(2-hydroxy-ethyl-methacrylate) based contact lenses. Contact lenses embedded with catanionic aggregates can achieve extended delivery of at least 1-week for two anionic drugs. Release kinetics is significantly dependent on the drug’s octanol-water partition coefficient, the hydrocarbon chain length and concentration of the cationic surfactant. Next, we focus on the use of unsaturated fatty acids in commercial contact lenses to extend the release of three cationic drugs. We demonstrate that lenses loaded with oleic acid can extend drug release kinetics to over 1 month. An opposite effect is seen for two anionic drugs, where oleic acid significantly accelerates release kinetics. These studies confirm the dominating impact of coupling charge interactions between drug molecules and fatty acid carrier molecules in contact lenses to adjust drug delivery rates. Finally, we extend the application of fatty acids in contact lenses to evaluate the effect of hydrocarbon chain length, ionic strength, and pH on the release kinetics. It is shown that fatty acids with carbon chain lengths equal or greater than 12 are capable of extending drug release of two cationic drugs, which confirms the importance of hydrophobic interactions with the silicone domain of the gel matrix. By decreasing ionic strength (from 1665 to 167 mM) or increasing the pH of the release media (from 5.5 to 7.4), release kinetics is significantly extended. In summary, the use of fatty acids to control the release of oppositely charged drug molecules represents a versatile tool to modify contact lenses for drug delivery applications.