The influence on the oral bioavailability of solubilized and suspended drug in a lipid nanoparticle formulation: In vitro and in vivo evaluation

Elbrink, Kimberley; Hees, Sofie Van; Roelant, Dirk; Loomans, Tine; Holm, René; Kiekens, Filip

doi:10.1016/j.ejpb.2022.08.010

Cited by 6 publications

(2 citation statements)

References 50 publications

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“…Low solubility hinders drug absorption, leading to poor bioavailability and reduced efficacy, which is especially problematic for insoluble drugs. 1 , 2 Oral nano-drug delivery systems have the potential to address the aforementioned issues, thereby enhancing bioavailability, improving targeting, and drug stability while simultaneously mitigating adverse reactions, which are considered significant areas in pharmacy research. 3 Celecoxib, an FDA-recommended non-steroidal anti-inflammatory drug in osteoarthritis clinical applications, 4 is a selective cyclooxygenase 2 inhibitor that exerts analgesic and anti-inflammatory effects through prostaglandin inhibition.…”

Section: Introductionmentioning

confidence: 99%

Revealing Changes in Celecoxib Nanostructured Lipid Carrier’s Bioavailability Using Hyaluronic Acid as an Enhancer by HPLC-MS/MS

Zhu,

Chen,

Yang

et al. 2024

DDDT

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Purpose Oral drug administration is the most common and convenient route, offering good patient compliance but drug solubility limits oral applications. Celecoxib, an insoluble drug, requires continuous high-dose oral administration, which may increase cardiovascular risk. The nanostructured lipid carriers prepared from drugs and lipid excipients can effectively improve drug bioavailability, reduce drug dosage, and lower the risk of adverse reactions. Methods In this study, we prepared hyaluronic acid-modified celecoxib nanostructured lipid carriers (HA-NLCs) to improve the bioavailability of celecoxib and reduce or prevent adverse drug reactions. Meanwhile, we successfully constructed a set of FDA-compliant biological sample test methods to investigate the pharmacokinetics of HA-NLCs in rats. Results The pharmacokinetic analysis confirmed that HA-NLCs significantly enhanced drug absorption, resulting in an AUC 0-t 1.54 times higher than the reference formulation (Celebrex ® ). Moreover, compared with unmodified nanostructured lipid carriers (CXB-NLCs), HA-NLCs enhance the retention time and improve the drug’s half-life in vivo. Conclusion HA-NLCs significantly increased the bioavailability of celecoxib. The addition of hyaluronic acid prolonged the drug’s in vivo duration of action and reduced the risk of cardiovascular adverse effects associated with the frequent administration of oral celecoxib.

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Section: Introductionmentioning

confidence: 99%

Revealing Changes in Celecoxib Nanostructured Lipid Carrier’s Bioavailability Using Hyaluronic Acid as an Enhancer by HPLC-MS/MS

Zhu,

Chen,

Yang

et al. 2024

DDDT

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“…This enhancement in oral bioavailability is attributed in part to a marked improvement in the apparent solubility of the drug. In addition, the small size of the SLN and NLC particles promotes a higher dissolution rate of the drug as well as lymphatic transport which provides a means to avoid first-pass metabolism [10,11].…”

Section: Introductionmentioning

confidence: 99%

Data-driven development of an oral lipid-based nanoparticle formulation of a hydrophobic drug

Bao,

Yung,

Hickman

et al. 2023

Drug Deliv. and Transl. Res.

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Due to its cost-effectiveness, convenience, and high patient adherence, oral drug administration often remains the preferred approach. Yet, the effective delivery of hydrophobic drugs via the oral route is often hindered by their limited water solubility and first-pass metabolism. To mitigate these challenges, advanced delivery systems such as solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) have been developed to encapsulate hydrophobic drugs and enhance their bioavailability. However, traditional design methodologies for these complex formulations often present intricate challenges because they are restricted to a relatively narrow design space. Here, we present a data-driven approach for the accelerated design of SLNs/NLCs encapsulating a model hydrophobic drug, cannabidiol, that combines experimental automation and machine learning. A small subset of formulations, comprising 10% of all formulations in the design space, was prepared in-house, leveraging miniaturized experimental automation to improve throughput and decrease the quantity of drug and materials required. Machine learning models were then trained on the data generated from these formulations and used to predict properties of all SLNs/NLCs within this design space (i.e., estimated to be more than 1200 formulations).Notably, formulations predicted to be high-performers via this approach were confirmed to significantly enhance the solubility of the drug by up to 3000-fold and prevent drug degradation. Moreover, our high-performance formulations significantly enhanced the oral bioavailability of the drug compared to both its free form and an over-the-counter version. Furthermore, this bioavailability matched that of a formulation equivalent in composition to the FDA-approved product, Epidiolex®.

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Optimization of the different phases of the freeze-drying process of solid lipid nanoparticles using experimental designs

Elbrink

Hees

Holm

et al. 2023

International Journal of Pharmaceutics

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The influence on the oral bioavailability of solubilized and suspended drug in a lipid nanoparticle formulation: In vitro and in vivo evaluation

Cited by 6 publications

References 50 publications

Revealing Changes in Celecoxib Nanostructured Lipid Carrier’s Bioavailability Using Hyaluronic Acid as an Enhancer by HPLC-MS/MS

Revealing Changes in Celecoxib Nanostructured Lipid Carrier’s Bioavailability Using Hyaluronic Acid as an Enhancer by HPLC-MS/MS

Data-driven development of an oral lipid-based nanoparticle formulation of a hydrophobic drug

Optimization of the different phases of the freeze-drying process of solid lipid nanoparticles using experimental designs

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