Cellular Uptake Mechanism of Paclitaxel Nanocrystals Determined by Confocal Imaging and Kinetic Measurement

Cao, Yan; Li, Tonglei

doi:10.1208/s12248-015-9774-0

Cited by 44 publications

(28 citation statements)

References 14 publications

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“…In addition, the small size may have helped PNC to enter cells. A recent study supports that drug nanocrystals could be endocytosed as solid particles [35]. …”

Section: Resultsmentioning

confidence: 93%

Intraperitoneal chemotherapy of ovarian cancer by hydrogel depot of paclitaxel nanocrystals

Sun

Taha

Ramsey

et al. 2016

Journal of Controlled Release

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Intraperitoneal (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.

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“…In addition, the small size may have helped PNC to enter cells. A recent study supports that drug nanocrystals could be endocytosed as solid particles [35]. …”

Section: Resultsmentioning

confidence: 93%

Intraperitoneal chemotherapy of ovarian cancer by hydrogel depot of paclitaxel nanocrystals

Sun

Taha

Ramsey

et al. 2016

Journal of Controlled Release

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“…7), suitable for intracellular imaging. It is well established that an organic dye such as rhodamine B can be stably incorporated in organic crystal lattice with minimal change in crystallization behavior [29], and NC similarly doped with fluorescent dyes have previously been used to visualize their cellular uptake [46]. To ensure that the incorporated rhodamine B represents Cim-F-alb, free rhodamine B was tested in parallel.…”

Section: Resultsmentioning

confidence: 99%

Albumin-coated nanocrystals for carrier-free delivery of paclitaxel

Park

Sun

Yeo

2017

Journal of Controlled Release

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Nanoparticles are used to deliver anticancer drugs to solid tumors. However, clinical development of nanoparticles is challenging because of their limitations in physicochemical properties, such as low drug loading efficiency and poor circulation stability. Low drug loading not only causes technical difficulty in administration but also increases the amount of co-delivered carrier materials, imposing biological burdens to patients. Poor circulation stability causes loss of pharmacokinetics benefits of nanoparticles. To overcome these challenges, we developed an albumin-coated nanocrystal (NC) formulation of paclitaxel (PTX) with 90% drug loading and high serum stability. The NC was produced by inducing crystallization of PTX in aqueous medium, coating the surface with albumin, and removing extra non-drug ingredients. Among three types of NC produced with different crystallization conditions, NC crystallized in the medium containing Pluronic F-127 then coated with albumin (“Cim-F-alb”) had the smallest size and the most native albumin, thus showing the most favorable cell interaction profiles (low uptake by J774A.1 macrophages and high uptake by SPARC+ B16F10 melanoma cells). Cim-F-alb remained more stable in undiluted serum than Abraxane, a commercial albumin-based PTX nanoparticle formulation, while maintaining comparable cytotoxicity to those of Abraxane and solvent-dissolved PTX. In a mouse model of B16F10 melanoma, Cim-F-alb showed higher antitumor efficacy than Abraxane at the same dose. This study demonstrates the feasibility and benefits of delivering an anticancer drug using a carrier-free nanoparticle formulation with good circulation stability.

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“…Sonvico et al showed that dextran coatings on maghemite NPs can achieve comparable disaggregation properties to PEG coatings and can be used to conjugate targeting moieties . It has also been shown that surface modifications can significantly affect the dissolution kinetics of pure drug NPs . Stiffness and surface texture are also known impact the in vivo performance of NPs .…”

Section: Preparation and Characterization Of Nanocrystalsmentioning

confidence: 99%

Nanocrystals: A perspective on translational research and clinical studies

Jarvis

Krishnan

Mitragotri

2018

Bioengineering & Transla Med

100

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Poorly soluble small molecules typically pose translational hurdles owing to their low solubility, low bioavailability, and formulation challenges. Nanocrystallization is a versatile method for salvaging poorly soluble drugs with the added benefit of a carrier‐free delivery system. In this review, we provide a comprehensive analysis of nanocrystals with emphasis on their clinical translation. Additionally, the review sheds light on clinically approved nanocrystal drug products as well as those in development.

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Cellular Uptake Mechanism of Paclitaxel Nanocrystals Determined by Confocal Imaging and Kinetic Measurement

Cited by 44 publications

References 14 publications

Intraperitoneal chemotherapy of ovarian cancer by hydrogel depot of paclitaxel nanocrystals

Intraperitoneal chemotherapy of ovarian cancer by hydrogel depot of paclitaxel nanocrystals

Albumin-coated nanocrystals for carrier-free delivery of paclitaxel

Nanocrystals: A perspective on translational research and clinical studies

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