Taha, M. S., A. Nocera, A. Workman, M. M. Amiji, and B. S. Bleier, "P-glycoprotein inhibition with verapamil overcomes mometasone resistance in Chronic Sinusitis with Nasal Polyps.", Rhinology, vol. 59, issue 2, pp. 205-211, 2021. Abstract

BACKGROUND: P-glycoprotein (P-gp) is a membrane efflux pump which is overexpressed in Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) and promotes Type 2 inflammation. Glucocorticoids (GC) are substrates of P-gp suggesting that overexpression may additionally contribute to GC resistance in CRSwNP. This study aims to determine whether P-gp inhibition using verapamil enhances mometasone retention and efficacy in nasal polyp explants.

METHODOLOGY: IRB approved study in which organotypic polyp explants were exposed to mometasone (4.15 μg/mL) and verapa- mil (125 μg/mL) as mono and combination therapy. The effect of verapamil on mometasone tissue retention over time was deter- mined using HPLC. The effect of verapamil on mometasone anti-inflammatory function was determined using ELISA for secreted IL-5. Groups were compared using Kruskal-Wallis test.

RESULTS: P-gp expression strongly and significantly inversely correlated with mometasone retention 1hr after exposure, with a ne- arly 6-fold reduction in tissue retention between the lowest and highest P-gp expressing polyp explants. P-gp inhibition reversed this effect and significantly improved mometasone retention at 1hr relative to mometasone alone. The combination of mome- tasone and verapamil significantly reduced IL-5 secretion relative to vehicle control and outperformed either treatment alone.

CONCLUSIONS: Our study confirms that P-gp contributes to mometasone resistance. This P-gp mediated resistance was successfully reversed by addition of the P-gp inhibitor verapamil. Verapamil further significantly enhanced the anti-inflammatory effect of mometasone when given as a combination therapy.

A., Y. S., K. Hyungjun, A. N. S., D. A. M., T. M. S., T. M. D., L. L. Tiffany, S. M. N., and Y. Yoon, "Nanocapsules modify membrane interaction of polymyxin B to enable safe systemic therapy of Gram-negative sepsis", Science Advances, vol. 7, issue 32: American Association for the Advancement of Science, pp. eabj1577, 2021. AbstractWebsite

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Taha, M. S., S. Padmakumar, A. Singh, and M. M. Amiji, Critical quality attributes in the development of therapeutic nanomedicines toward clinical translation, , vol. 10, issue 3, pp. 766 - 790, 2020. AbstractWebsite

Nanomedicine is a rapidly emerging field with several breakthroughs in the therapeutic drug delivery application. The unique properties of the nanoscale delivery systems offer huge advantages to their payload such as solubilization, increased bioavailability, and improved pharmacokinetics with an overall goal of enhanced therapeutic index. Nanomedicine has the potential for integrating and enabling new therapeutic modalities. Several nanoparticle-based drug delivery systems have been granted approval for clinical use based on their outstanding clinical outcomes. Nanomedicine faces several challenges that hinder the realization of its full potential. In this review, we discuss the critical formulation- and biological-related quality features that significantly influence the performance of nanoparticulate systems in vivo. We also discuss the quality-by-design approach in the pharmaceutical manufacturing and its implementation in the nanomedicine. A deep understanding of these nanomedicine quality checkpoints and a systematic design that takes them into consideration will hopefully expedite the clinical translation process.

Padmakumar, S., M. S. Taha, E. Kadakia, B. S. Bleier, and M. M. Amiji, "Delivery of neurotrophic factors in the treatment of age-related chronic neurodegenerative diseases", Expert Opinion on Drug DeliveryExpert Opinion on Drug Delivery, vol. 17, issue 3: Taylor & Francis, pp. 323 - 340, 2020. AbstractWebsite
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Taha, M. S., G. M. Cresswell, J. Park, W. Lee, T. L. Ratliff, and Y. Yeo, "Sustained Delivery of Carfilzomib by Tannic Acid-Based Nanocapsules Helps Develop Antitumor Immunity", Nano LettersNano Letters, vol. 19, issue 11: American Chemical Society, pp. 8333 - 8341, 2019. AbstractWebsite
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Sun, B., M. S. Taha, B. Ramsey, S. Torregrosa-Allen, B. D. Elzey, and Y. Yeo, Intraperitoneal chemotherapy of ovarian cancer by hydrogel depot of paclitaxel nanocrystals, , vol. 235, pp. 91 - 98, 2016/8/10/. AbstractWebsite

AbstractIntraperitoneal (IP) chemotherapy is a promising post-surgical therapy of ovarian cancer, but the full potential is yet to be realized. To facilitate IP chemotherapy of ovarian cancer, we developed an in-situ crosslinkable hydrogel depot containing paclitaxel (PTX) nanocrystals (PNC). PNC suppressed SKOV3 cell proliferation more efficiently than microparticulate PTX precipitates (PPT), and the gel containing PNC (PNC-gel) showed a lower maximum tolerated dose than PPT-containing gel (PPT-gel) in mice, indicating greater dissolution and cellular uptake of PNC than PPT. A single IP administration of PNC-gel extended the survival of tumor-bearing mice significantly better than Taxol, but PPT-gel did not. These results support the advantage of PNC over PPT and demonstrate the promise of a gel depot as an IP drug delivery system.

Elmahrouk, G. M., O. N. Elgazayerly, A. A. Aboelwafa, and M. S. Taha, "Hot-melts in buccoadhesive patches: An approach for bioavailability enhancement of highly-metabolized drugs with short elimination half-life", European Journal of Pharmaceutics and Biopharmaceutics, 2014.
El-Mahrouk, G. M., O. N. El-Gazayerly, A. A. Aboelwafa, and M. S. Taha, "Chitosan lactate wafer as a platform for the buccal delivery of tizanidine hydrochloride: in vitro and in vivo performance.", International Journal of Pharmaceutics, vol. 467, issue 1, pp. 100-112, 2014.