Polymeric micelles as drug delivery vehicles

Ahmad, Zaheer; Shah, Afzal; Siddiq, Muhammad; Kraatz, Heinz‐Bernhard

doi:10.1039/c3ra47370h

Cited by 479 publications

(329 citation statements)

References 103 publications

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“…The average sizes were generally in the same range of 100-120 nm, which is conducive to a satisfactory drug accumulation in the tumor through the enhanced permeability and retention (EPR) effect. 41 The polydispersity of DOX/TPL-1/0.2-LPNPs was 0.12, indicating an unimodal size distribution.…”

Section: Size Morphology and Drug Loadingmentioning

confidence: 99%

Codelivery of doxorubicin and triptolide with reduction-sensitive lipid–polymer hybrid nanoparticles for in vitro and in vivo synergistic cancer treatment

Wu¹,

Lu²,

Zhang³

et al. 2017

IJN

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Codelivery is a promising strategy to overcome the limitations of single chemotherapeutic agents in cancer treatment. Despite progress, codelivery of two or more different functional drugs to increase anticancer efficiency still remains a challenge. Here, reduction-sensitive lipid–polymer hybrid nanoparticles (LPNPs) drug delivery system composed of monomethoxy-poly(ethylene glycol)- S - S -hexadecyl (mPEG- S - S -C 16 ), soybean lecithin, and poly(D,L-lactide-co-glycolide) (PLGA) was used for codelivery of doxorubicin (DOX) and a Chinese herb extract triptolide (TPL). Hydrophobic DOX and TPL could be successfully loaded in LPNPs by self-assembly. More importantly, drug release and cellular uptake experiments demonstrated that the two drugs were reduction sensitive, released simultaneously from LPNPs, and taken up effectively by the tumor cells. DOX/TPL-coloaded LPNPs (DOX/TPL-LPNPs) exhibited a high level of synergistic activation with low combination index (CI) in vitro and in vivo. Moreover, the highest synergistic therapeutic effect was achieved at the ratio of 1:0.2 DOX/TPL. Further experiments showed that TPL enhanced the uptake of DOX by human oral cavity squamous cell carcinoma cells (KB cells). Overall, DOX/TPL-coencapsulated reduction-sensitive nanoparticles will be a promising strategy for cancer treatment.

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Section: Size Morphology and Drug Loadingmentioning

confidence: 99%

Codelivery of doxorubicin and triptolide with reduction-sensitive lipid–polymer hybrid nanoparticles for in vitro and in vivo synergistic cancer treatment

Wu¹,

Lu²,

Zhang³

et al. 2017

IJN

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“…A number of carrier vehicles exist that are capable of sequestering a strongly hydrophobic compound within the core of a particle measuring several tens of nanometers in diameter, which are dispersible in water. 26 It is possible for these particulates to disseminate through the body and be taken up by cells, whereupon the drug payload is delivered by cellular mechanisms to the target site, facilitating bypass of the major efflux transporters of the BBB. 27 Poloxamer 407 (P407) is an FDA-approved triblock copolymer consisting of hydrophobic polypropylene glycol units terminated at each end by hydrophilic polyethylene glycol chains.…”

Section: Introductionmentioning

confidence: 99%

Convection enhanced delivery of panobinostat (LBH589)-loaded pluronic nano-micelles prolongs survival in the F98 rat glioma model

Singleton¹,

Collins²,

Bienemann³

et al. 2017

IJN

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Background The pan-histone deacetylase inhibitor panobinostat is a potential therapy for malignant glioma, but it is water insoluble and does not cross the blood–brain barrier when administered systemically. In this article, we describe the in vitro and in vivo efficacy of a novel water-soluble nano-micellar formulation of panobinostat designed for administration by convection enhanced delivery (CED). Materials and methods The in vitro efficacy of panobinostat-loaded nano-micelles against rat F98, human U87-MG and M059K glioma cells and against patient-derived glioma stem cells was measured using a cell viability assay. Nano-micelle distribution in rat brain was analyzed following acute CED using rhodamine-labeled nano-micelles, and toxicity was assayed using immunofluorescent microscopy and synaptophysin enzyme-linked immunosorbent assay. We compared the survival of the bioluminescent syngenic F98/Fischer344 rat glioblastoma model treated by acute CED of panobinostat-loaded nano-micelles with that of untreated and vehicle-only-treated controls. Results Nano-micellar panobinostat is cytotoxic to rat and human glioma cells in vitro in a dose-dependent manner following short-time exposure to drug. Fluorescent rhodamine-labelled nano-micelles distribute with a volume of infusion/volume of distribution (Vi/Vd) ratio of four and five respectively after administration by CED. Administration was not associated with any toxicity when compared to controls. CED of panobinostat-loaded nano-micelles was associated with significantly improved survival when compared to controls (n=8 per group; log-rank test, P <0.001). One hundred percent of treated animals survived the 60-day experimental period and had tumour response on post-mortem histological examination. Conclusion CED of nano-micellar panobinostat represents a potential novel therapeutic option for malignant glioma and warrants translation into the clinic.

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“…Polymer micelles are highly efficient in entrapping hydrophobic drug molecules inside the core to prevent the drugs from precipitating, binding to serum proteins, or being degraded by enzymes in the body (Sanvicens and Marco, 2008). Additionally, polymer micelles are readily modified chemically or with attachment of surface ligands to control drug release patterns as well as cell-targeted drug delivery, making them versatile vehicles for delivery (Zhang et al, 2008;Ahmad et al, 2014). Previous studies have also shown that polymer micelles can significantly reduce toxicity and improve anticancer activity of chemotherapeutics by achieving sustained drug release and increasing drug exposure to cancer cells (Tan et al, 2013;Werner et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Polymer Micelle Formulations of Proteasome Inhibitor Carfilzomib for Improved Metabolic Stability and Anticancer Efficacy in Human Multiple Myeloma and Lung Cancer Cell Lines

Reichel

et al. 2015

J Pharmacol Exp Ther

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Carfilzomib (CFZ) is a second-generation proteasome inhibitor drug approved for the treatment of multiple myeloma. Contrary to its excellent antimyeloma activity, CFZ has shown only limited efficacy in patients with solid malignancies. This lack of efficacy has been attributed in part to rapid degradation of CFZ in the body, possibly hindering the ability of CFZ to access the proteasome target in solid tumors. We hypothesized that polymer micelles, a currently Food and Drug Administration-approved nanoparticle drug delivery formulation, may protect CFZ from metabolic degradation and thus expand the clinical utility of the drug as an anticancer agent. To test our hypothesis, we prepared CFZ-entrapped polymer micelle particles with various compositions and drug release profiles and examined the extent of the CFZ metabolism in vitro using mouse liver homogenates. We also assessed the cytotoxic activities of the CFZ-entrapped micelle formulations in human cancer cell lines derived from B lymphocytes (RPMI-8226) and the lung (H460). Our data indicated that polymer micelle-based formulations can improve metabolic stability and cytotoxic effects of CFZ compared with free CFZ in human cancer cell lines tested. Taken together, these results suggest that polymer micelles may have potential as a delivery system for CFZ with an extended therapeutic utility for nonhematologic malignancies in the future.

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Polymeric micelles as drug delivery vehicles

Abstract: Though much progress has been made in drug delivery systems, the design of a suitable carrier for the delivery of hydrophobic drugs is still a major challenge for researchers.

Cited by 479 publications

References 103 publications

Codelivery of doxorubicin and triptolide with reduction-sensitive lipid–polymer hybrid nanoparticles for in vitro and in vivo synergistic cancer treatment

Codelivery of doxorubicin and triptolide with reduction-sensitive lipid–polymer hybrid nanoparticles for in vitro and in vivo synergistic cancer treatment

Convection enhanced delivery of panobinostat (LBH589)-loaded pluronic nano-micelles prolongs survival in the F98 rat glioma model

Polymer Micelle Formulations of Proteasome Inhibitor Carfilzomib for Improved Metabolic Stability and Anticancer Efficacy in Human Multiple Myeloma and Lung Cancer Cell Lines

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Polymeric micelles as drug delivery vehicles

Abstract: Though much progress has been made in drug delivery systems, the design of a suitable carrier for the delivery of hydrophobic drugs is still a major challenge for researchers.

Cited by 479 publications

References 103 publications

Codelivery of doxorubicin and triptolide with reduction-sensitive lipid&ndash;polymer hybrid nanoparticles for in vitro and in vivo synergistic cancer treatment

Codelivery of doxorubicin and triptolide with reduction-sensitive lipid&ndash;polymer hybrid nanoparticles for in vitro and in vivo synergistic cancer treatment

Convection enhanced delivery of panobinostat (LBH589)-loaded pluronic nano-micelles prolongs survival in the F98 rat glioma model

Polymer Micelle Formulations of Proteasome Inhibitor Carfilzomib for Improved Metabolic Stability and Anticancer Efficacy in Human Multiple Myeloma and Lung Cancer Cell Lines

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Resources

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Codelivery of doxorubicin and triptolide with reduction-sensitive lipid–polymer hybrid nanoparticles for in vitro and in vivo synergistic cancer treatment

Codelivery of doxorubicin and triptolide with reduction-sensitive lipid–polymer hybrid nanoparticles for in vitro and in vivo synergistic cancer treatment