A rigorous theory of remote loading of drugs into liposomes

Čeh, B.; Lasic, D. D.

doi:10.1021/la00009a016

Cited by 42 publications

(23 citation statements)

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“…3). This was consistent with previous results [33,43] and can be attributed to two factors: the lipid composition and method of DXR loading. The cholesterol formulation for L-DXR exhibits resistance to strong shear forces, which aid in withstanding forces applied during the extrusion process [33]; thus, providing liposomal stability when encapsulating DXR.…”

Section: Discussionsupporting

confidence: 93%

E-selectin liposomal and nanotube-targeted delivery of doxorubicin to circulating tumor cells

Mitchell

Chen

Ponmudi

et al. 2012

Journal of Controlled Release

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The presence of circulating tumor cells (CTCs) is believed to lead to the formation of secondary tumors via an adhesion cascade involving interaction between adhesion receptors of endothelial cells and ligands on CTCs. Many CTCs express sialylated carbohydrate ligands on their surfaces that adhere to selectin protein found on inflamed endothelial cells. We have investigated the feasibility of using immobilized selectin proteins as a targeting mechanism for CTCs under flow. Herein, targeted liposomal doxorubicin (L-DXR) was functionalized with recombinant human E-selectin (ES) and polyethylene glycol (PEG) to target and kill cancer cells under shear flow, both when immobilized along a microtube device or sheared in a cone-and-plate viscometer in a dilute suspension. Healthy circulating cells such as red blood cells were not targeted by this mechanism and were left to freely circulate, and minimal leukocyte death was observed. Halloysite nanotube (HNT)-coated microtube devices immobilized with nanoscale liposomes significantly enhanced the targeting, capture, and killing of cancer cells. This work demonstrates that E-selectin functionalized L-DXR, sheared in suspension or immobilized onto microtube devices, provides a novel approach to selectively target and deliver chemotherapeutics to CTCs in the bloodstream.

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Section: Discussionsupporting

confidence: 93%

E-selectin liposomal and nanotube-targeted delivery of doxorubicin to circulating tumor cells

Mitchell

Chen

Ponmudi

et al. 2012

Journal of Controlled Release

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“…[27][28][29][30] The DXR stock solution (5 mg/mL) was mixed with the stock liposome at the ratio of 1 : 1 (v/v), and diluted with the diluent to obtain 2 mg/mL of DXR. The obtained suspension was annealed with occasional shaking in a water bath maintained at 60°C for 5 min.…”

Section: Preparation Of Dxr Liposomesmentioning

confidence: 99%

Characterization of a Doxorubicin Liposome Formulation by a Novel <i>in Vitro</i> Release Test Methodology Using Column-Switching High-Performance Liquid Chromatography

et al. 2014

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A novel in vitro release test methodology for a liposome formulation was developed using a columnswitching high-performance liquid chromatography (HPLC) system. Doxorubicin (DXR) liposome formulations were used as a model. A DXR liposome formulation was dispersed into a release medium, and the dispersion fluid was directly injected at predetermined time points into the column-switching HPLC system. To evaluate the release profile, this system can be used for determining the released and encapsulated DXR in the liposome formulation separately. Comparison with a conventional in vitro release test methodology by dialysis revealed that the methodology developed by column-switching HPLC had no rate-limiting process of membrane permeation of the drug (which is occasionally observed in the dialysis method). The in vitro release profiles of DXR liposome formulations were well characterized using the method developed by column-switching HPLC, and different in vitro release characteristics were revealed. The developed method did not require a large amount of sample or a complicated pretreatment. In addition, the developed columnswitching HPLC system was applicable for characterization of the encapsulation profile of liposome formulations.Key words doxorubicin; Doxil ® ; dialysis; solid-phase extraction; encapsulation Several studies of pharmaceutical formulations for drugdelivery systems (DDS), such as liposomes, microspheres, and nanosuspensions, have been conducted. Their advantages, such as targeted/controlled delivery, enhanced efficacy, and reduced toxicity, have been verified. [1][2][3][4] However, the number of approved and marketed pharmaceutical products with DDS technology is limited. The reasons for this are thought to be the difficulty of robust mass production as well as the lack of sophisticated quality control accompanied by a deep understanding of in vitro and in vivo characteristics. With regard to liposome formulations, the enhanced permeability and retention (EPR) effect of polyethylene glycol-conjugated liposomes has been demonstrated in several studies, and are very attractive as passive targeting methods of antitumor agents. [5][6][7][8][9] Considerable efforts are being made for the development of several administration routes for liposomes, such as inhalational, transdermal, and ocular in addition to injection. [10][11][12][13][14] In contrast, analytical technology for liposome formulations may not be sufficiently mature to assure efficacy and safe performance as well as to direct the optimization of formulations or improvements in manufacturing processes. Drug release characteristics are considered to be one of the important properties to assure the performance of liposome formulations. 15)These characteristics may change depending on the lot-to-lot variation of ingredients and/or changes in manufacturing processes such as scale-up. The importance of evaluation of the in vitro release characteristics is increasing and it is one of the regulatory requirements. [16][17][18][19] Although in vitro re...

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“…While many models have been developed to describe drug loading [21-24], few have considered release kinetics [25-27] and even fewer have been validated experimentally [21, 26, 27]. Mechanistic models that incorporate physicochemical properties of the drug in solution including the drug species present as a function of intraliposomal pH, their interactions with the lipid bilayer, and their membrane permeabilities would be essential to release rate design and optimization.…”

Section: Introductionmentioning

confidence: 99%

The role of pH and ring-opening hydrolysis kinetics on liposomal release of topotecan

Fugit

Anderson

2014

Journal of Controlled Release

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A rigorous theory of remote loading of drugs into liposomes

Cited by 42 publications

References 0 publications

E-selectin liposomal and nanotube-targeted delivery of doxorubicin to circulating tumor cells

E-selectin liposomal and nanotube-targeted delivery of doxorubicin to circulating tumor cells

Characterization of a Doxorubicin Liposome Formulation by a Novel <i>in Vitro</i> Release Test Methodology Using Column-Switching High-Performance Liquid Chromatography

The role of pH and ring-opening hydrolysis kinetics on liposomal release of topotecan

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