Nanosized particles of orlistat with enhanced in vitro dissolution rate and lipase inhibition

Dolenc, Andrej; Govedarica, Biljana; Dreu, Rok; Kocbek, Petra; Srčič, Stanko; Kristl, Julijana

doi:10.1016/j.ijpharm.2010.06.003

Cited by 40 publications

(34 citation statements)

References 23 publications

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“…NP formulations of orlistat show promise for improved cytotoxicity and delivery to tumors as demonstrated by us (37) and others (54–56). Paulmurugan et al .…”

Section: Discussionmentioning

confidence: 70%

Combination Treatment with Orlistat-Containing Nanoparticles and Taxanes Is Synergistic and Enhances Microtubule Stability in Taxane-Resistant Prostate Cancer Cells

Souchek

Davis

Hill

et al. 2017

Molecular Cancer Therapeutics

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Taxane-based therapy provides a survival benefit in patients with metastatic prostate cancer, yet the median survival is less than 20 months in this setting due in part to taxane-associated resistance. Innovative strategies are required to overcome chemoresistance for improved patient survival. Here, NanoOrl, a new experimental nanoparticle formulation of the FDA-approved drug, orlistat, was investigated for its cytotoxicity in taxane-resistant prostate cancer utilizing two established taxane-resistant (TxR) cell lines. Orlistat is a weight loss drug that inhibits gastric lipases, but is also a potent inhibitor of fatty acid synthase (FASN), which is overexpressed in many types of cancer. NanoOrl was also investigated for its potential to synergize with taxanes in TxR cell lines. Both orlistat and NanoOrl synergistically inhibited cell viability when combined with paclitaxel, docetaxel, and cabazitaxel in PC3-TxR and DU145-TxR cells, yet these combinations were also additive in parental lines. We observed synergistic levels of apoptosis in TxR cells treated with NanoOrl and docetaxel in combination. Mechanistically, the synergy between orlistat and taxanes was independent of effects on the P-glycoprotein multidrug resistance protein, as determined by an efflux activity assay. On the other hand, immunoblot and immunofluorescence staining with an anti-detyrosinated tubulin antibody demonstrated that enhanced microtubule stability was induced by combined NanoOrl and docetaxel treatment in TxR cells. Furthermore, TxR cells exhibited higher lipid synthesis, as demonstrated by 14C-choline incorporation, that was abrogated by NanoOrl. These results provide a strong rationale to assess the translational potential of NanoOrl to overcome taxane resistance.

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“…NP formulations of orlistat show promise for improved cytotoxicity and delivery to tumors as demonstrated by us (37) and others (54–56). Paulmurugan et al .…”

Section: Discussionmentioning

confidence: 70%

Combination Treatment with Orlistat-Containing Nanoparticles and Taxanes Is Synergistic and Enhances Microtubule Stability in Taxane-Resistant Prostate Cancer Cells

Souchek

Davis

Hill

et al. 2017

Molecular Cancer Therapeutics

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“…Results further conclude that SMEDDS formulation of lipophilic drug like orlistat has potential for increased bioavailability and can be explored as good alternative to conventional formulations. [12]…”

Section: Resultsmentioning

confidence: 99%

Design, development and optimization of selfmicroemulsifying drug delivery system of an anti-obesity drug

et al. 2012

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The aim of the present work was to formulate a self-microemulsifying drug delivery system (SMEDDS) containing orlistat. The oil, surfactant and co-surfactant were decided based on the solubility studies. Pseudoternary phase diagrams were plotted, microemulsification area was determined and different formulations were prepared. Particle size, zeta potential, dispersibility test and thermodynamic stability studies were measured. In-vitro dissolution test of thermodynamically stable formulations OS-B and OS-C were carried and results were compared with those of plain drug and suspension formulation. Stability studies performed indicated that formulation OS-C remained stable over 12 months period. Thus this investigation concluded that hydrophobic drugs like orlistat can be delivered effectively through the formulation of SMEDDS.

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“…A discriminating in vitro drug dissolution test plays an important role in pharmaceutical product development as it may be used as a representative tool for the assessment of formulation performance in vivo . Results of the dissolution studies for nanocrystalline formulations have been documented in several reports where studies were carried out under sink conditions . At sink condition, nanocrystals dissolve instantaneously, which hinders the discrimination of dissolution behavior with respect to different particle size.…”

Section: Introductionmentioning

confidence: 99%

Impact of Nanosizing on Solubility and Dissolution Rate of Poorly Soluble Pharmaceuticals

Murdande

Shah

Dave

2015

Journal of Pharmaceutical Sciences

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Nanosized particles of orlistat with enhanced in vitro dissolution rate and lipase inhibition

Cited by 40 publications

References 23 publications

Combination Treatment with Orlistat-Containing Nanoparticles and Taxanes Is Synergistic and Enhances Microtubule Stability in Taxane-Resistant Prostate Cancer Cells

Combination Treatment with Orlistat-Containing Nanoparticles and Taxanes Is Synergistic and Enhances Microtubule Stability in Taxane-Resistant Prostate Cancer Cells

Design, development and optimization of selfmicroemulsifying drug delivery system of an anti-obesity drug

Impact of Nanosizing on Solubility and Dissolution Rate of Poorly Soluble Pharmaceuticals

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