Publications -- Xiaowei Dong

Permanent URI for this collectionhttps://hdl.handle.net/20.500.12503/31738

This collection is limited to articles published under the terms of a creative commons license or other open access publishing agreement since 2016. It is not intended as a complete list of the author's works.

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    The Development of Lipid-Based Sorafenib Granules to Enhance the Oral Absorption of Sorafenib
    (MDPI, 2023-12-23) Mans, Jaylen C.; Dong, Xiaowei
    Sorafenib (SFN) is an anticancer multi-kinase inhibitor with great therapeutic potential. However, SFN has low aqueous solubility, which limits its oral absorption. Lipids and surfactants have the potential to improve the solubility of water-insoluble drugs. The aim of this study is thus to develop novel lipid-based SFN granules that can improve the oral absorption of SFN. SFN powder was coated with a stable binary lipid mixture and then absorbed on Aeroperl 300 to form dry SFN granules with 10% drug loading. SFN granules were stable at room temperature for at least three months. Compared to SFN powder, SFN granules significantly increased SFN release in simulated gastric fluid and simulated intestinal fluid with pancreatin. Pharmacokinetics and tissue distribution of SFN granules and SFN powder were measured following oral administration to Sprague Dawley rats. SFN granules significantly increased SFN absorption compared to SFN powder. Overall, the lipid-based SFN granules provide a promising approach to enhancing the oral absorption of SFN.
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    The stability of quetiapine oral suspension compounded from commercially available tablets
    (PLOS, 2021-08-10) Tran, Jennie; Gervase, Melissa A.; Evans, Jason; Deville, Rebecca; Dong, Xiaowei
    Quetiapine fumarate (QF) is an atypical antipsychotic used off-label for the treatment of delirium in critically-ill infants and children. For the treatment of pediatric populations or patient populations with trouble swallowing tablets, an oral suspension would be an ideal dosage formulation. However, there are no liquid formulations of QF commercially available. Therefore, a compounded oral suspension prepared from the commercial QF tablets is widely used in clinical settings. The extemporaneous preparation of QF compounded oral suspension changes the formulation from a solid form to a liquid form. Thus, the stability of QF compounded oral suspension should be critically evaluated to guide pharmacists for administration and storage of QF compounded oral suspensions. However, the stability of the nonaqueous oral QF suspension was not measured. The objective of this study was to develop QF compounded oral suspensions at 10 mg/mL by using commercial QF tablets in two readily available aqueous vehicles (Ora-Sweet and Ora-Blend) and measure their stability at both room temperature and under refrigeration. Physical stability of the QF compounded suspensions were evaluated by appearance and odor. Chemical stability of the QF compounded suspensions were evaluated based on pH, degradation, drug content and the amount of the drug dissolved in the vehicles. An HPLC method was validated and used to evaluate QF compounded suspensions over 60 days. In addition to the total drug in the suspensions, the dissolved drug in the vehicles was also measured during the stability testing and evaluated as a stability parameter. Overall, QF suspension prepared in Ora-Blend was preferable, demonstrating a superior 60-day stability at both room temperature and refrigerated storage.
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    Curcumin Nanoparticles and Their Cytotoxicity in Docetaxel-Resistant Castration-Resistant Prostate Cancer Cells
    (MDPI, 2020-07-30) Tanaudommongkon, Irin; Tanaudommongkon, Asama; Prathipati, Priyanka; Nguyen, Joey Trieu; Keller, Evan T.; Dong, Xiaowei
    Most prostate cancer patients develop resistance to anti-androgen therapy. This is referred to as castration-resistant prostate cancer (CRPC). Docetaxel (DTX) is the mainstay treatment against CRPC. However, over time patients eventually develop DTX resistance, which is the cause of the cancer-related mortality. Curcumin (CUR) as a natural compound has been shown to have very broad pharmacological activities, e.g., anti-inflammatory and antioxidant properties. However, CUR is very hydrophobic. The objective of this study was to develop CUR nanoparticles (NPs) and evaluate their cytotoxicity in DTX-resistant CRPC cells for the treatment of DTX-resistant CRPC. We tested solubility of CUR in different lipids and surfactants. Finally, Miglyol 812 and D-alpha-tocopheryl poly (ethylene glycol) succinate 1000 (TPGS) were chosen to prepare lipid-based NPs for CUR. We fully characterized CUR NPs that had particle size < 150 nm, high drug loading (7.5%), and entrapment efficiency (90%). Moreover, the CUR NPs were successfully lyophilized without using cryoprotectants. We tested the cytotoxicity of blank NPs, free CUR, and CUR NPs in sensitive DU145 and PC3 cells as well as their matching docetaxel-resistant cells. Cytotoxicity studies showed that blank NPs were very safe for all tested prostate cancer cell lines. Free CUR overcame the resistance in PC3 cells, but not in DU145 cells. In contrast, CUR NPs significantly increased CUR potency in all tested cell lines. Importantly, CUR NPs completely restored CUR potency in both resistant DU145 and PC3 cells. These results demonstrate that the CUR NPs have potential to overcome DTX resistance in CRPC.
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    Current Strategies for Brain Drug Delivery
    (Ivyspring International Publisher, 2018-02-05) Dong, Xiaowei
    The blood-brain barrier (BBB) has been a great hurdle for brain drug delivery. The BBB in healthy brain is a diffusion barrier essential for protecting normal brain function by impeding most compounds from transiting from the blood to the brain; only small molecules can cross the BBB. Under certain pathological conditions of diseases such as stroke, diabetes, seizures, multiple sclerosis, Parkinson's disease and Alzheimer disease, the BBB is disrupted. The objective of this review is to provide a broad overview on current strategies for brain drug delivery and related subjects from the past five years. It is hoped that this review could inspire readers to discover possible approaches to deliver drugs into the brain. After an initial overview of the BBB structure and function in both healthy and pathological conditions, this review re-visits, according to recent publications, some questions that are controversial, such as whether nanoparticles by themselves could cross the BBB and whether drugs are specifically transferred to the brain by actively targeted nanoparticles. Current non-nanoparticle strategies are also reviewed, such as delivery of drugs through the permeable BBB under pathological conditions and using non-invasive techniques to enhance brain drug uptake. Finally, one particular area that is often neglected in brain drug delivery is the influence of aging on the BBB, which is captured in this review based on the limited studies in the literature.
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    Development of In Situ Self-Assembly Nanoparticles to Encapsulate Lopinavir and Ritonavir for Long-Acting Subcutaneous Injection
    (MDPI, 2021-06-18) Tanaudommongkon, Irin; Tanaudommongkon, Asama; Dong, Xiaowei
    Most antiretroviral medications for human immunodeficiency virus treatment and prevention require high levels of patient adherence, such that medications need to be administered daily without missing doses. Here, a long-acting subcutaneous injection of lopinavir (LPV) in combination with ritonavir (RTV) using in situ self-assembly nanoparticles (ISNPs) was developed to potentially overcome adherence barriers. The ISNP approach can improve the pharmacokinetic profiles of the drugs. The ISNPs were characterized in terms of particle size, drug entrapment efficiency, drug loading, in vitro release study, and in vivo pharmacokinetic study. LPV/RTV ISNPs were 167.8 nm in size, with a polydispersity index of less than 0.35. The entrapment efficiency was over 98% for both LPV and RTV, with drug loadings of 25% LPV and 6.3% RTV. A slow release rate of LPV was observed at about 20% on day 5, followed by a sustained release beyond 14 days. RTV released faster than LPV in the first 5 days and slower than LPV thereafter. LPV trough concentration remained above 160 ng/mL and RTV trough concentration was above 50 ng/mL after 6 days with one subcutaneous injection. Overall, the ISNP-based LPV/RTV injection showed sustained release profiles in both in vitro and in vivo studies.