Synthesis and in vitro evaluation of novel lipophilic monophosphorylated gemcitabine derivatives and their nanoparticles

Lansakara-P, Dharmika S.P.; Rodriguez, B. Leticia; Cui, Zhengrong

doi:10.1016/j.ijpharm.2012.03.014

Cited by 43 publications

(44 citation statements)

References 41 publications

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“…In this method, drug-loaded carriers are physically separated from the bulk media by a dialysis membrane, and the release is generally assessed from the outer bulk over time. 3,6 This technique has been used to study a variety of formulations, including liposomes and nanoparticles, [7][8][9][10][11][12][13][14][15] and it is almost exclusively used in the literature for the measurement of release kinetics. 6 It is a well-established technique, and although still widely used in the literature, it has been shown to suffer from significant limitations; therefore, it provides an inaccurate indication of the release kinetics of nanocarrier formulations.…”

Section: Huamentioning

confidence: 99%

Comparison of in vitro dialysis release methods of loperamide-encapsulated liposomal gel for topical drug delivery

Hua¹

2014

IJN

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Background The purpose of this study was to determine the most appropriate dialysis equilibrium method to assess liposomal gel formulations containing hydrophobic drugs, to give the most accurate indication of drug release. Methods Loperamide hydrochloride-encapsulated liposomes, composed of L-α-phosphatidylcholine and cholesterol (molar ratio of 2:1), were prepared according to the method of dried lipid film hydration. The liposomes were incorporated into a carbopol gel (0.5%, weight/weight). The release of the drug from the nanoparticles was assessed using a number of variations of the dialysis technique, taking into account solubility parameters and formulation. Method 1 (below saturation point) and Method 2 (above saturation point) used a dilution method to evaluate how drug concentration and solubility affects the in vitro drug-release profile of loperamide hydrochloride, while Methods 3 (below saturation point) and 4 (above saturation point) evaluated how drug concentration and the gel base affect the release profile. Results In Method 1, the liposomes showed a rapid release of just over 60% in the first 3 hours and then a slower, sustained release to just over 70% at 24 hours. Method 2 showed a gradual, sustained release profile with the liposomes with 55% release at 24 hours. In Method 3, the liposomes showed a rapid burst release of 98% at 2 hours. In Method 4, the liposomal gel had a rapid release of 60% within 3 hours and then a more gradual, sustained release with 86% release at 24 hours. The free drug suspension in Methods 2 and 4 showed a limited release across the dialysis membrane, in comparison to Methods 1 and 3, which showed a complete release in a timely manner. Conclusion This study has demonstrated that the actual method used for equilibrium dialysis plays a significant role in determining the true characteristics of a topical nanoformulation, with Method 3 providing the most accurate indication of the release of a hydrophobic drug from a topical liposomal formulation.

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Section: Huamentioning

confidence: 99%

Comparison of in vitro dialysis release methods of loperamide-encapsulated liposomal gel for topical drug delivery

Hua¹

2014

IJN

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“…This property was also demonstrated, in various cancer cell lines, with a lipophilic-gemcitabine derivate loaded in solid lipid nanoparticles. 39 A cell toxicity of THP-T80-LNCs was observed at high concentrations on HL-60 cells and was probably due to the presence of THP and Kolliphor ® HS15 in THP-T80-LNCs composition, well known to be toxic at high concentration. …”

mentioning

confidence: 92%

Development and in vitro evaluations of new decitabine nanocarriers for the treatment of acute myeloid leukemia

Briot

Roger

Lautram

et al. 2017

IJN

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“…[177][178][179][180] For example, it was shown that conjugation of a fatty acid, such as stearic acid, to gemcitabine at the 4-N position decreases the sensitivity of the later to deaminase. 181,182 In addition, gemcitabine-fatty acid conjugates formulated into nanoparticles also become less sensitive to deamination, as they are no longer good substrates of CDAs. 182 Meng et al developed a MSNP for co-delivery of gemcitabine and paclitaxel to take advantage of paclitaxel's ability to inhibit CDA expression to increase tumor response to gemcitabine.…”

Section: Reducing Deamination Of Gemcitabinementioning

confidence: 99%

“…181,182 In addition, gemcitabine-fatty acid conjugates formulated into nanoparticles also become less sensitive to deamination, as they are no longer good substrates of CDAs. 182 Meng et al developed a MSNP for co-delivery of gemcitabine and paclitaxel to take advantage of paclitaxel's ability to inhibit CDA expression to increase tumor response to gemcitabine. 183 …”

Section: Reducing Deamination Of Gemcitabinementioning

confidence: 99%

Overcoming tumor cell chemoresistance using nanoparticles: lysosomes are beneficial for (stearoyl) gemcitabine-incorporated solid lipid nanoparticles

Chen¹,

Zheng²,

Shi³

et al. 2018

IJN

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Despite recent advances in targeted therapies and immunotherapies, chemotherapy using cytotoxic agents remains an indispensable modality in cancer treatment. Recently, there has been a growing emphasis in using nanomedicine in cancer chemotherapy, and several nanomedicines have already been used clinically to treat cancers. There is evidence that formulating small molecular cancer chemotherapeutic agents into nanomedicines significantly modifies their pharmacokinetics and often improves their efficacy. Importantly, cancer cells often develop resistance to chemotherapy, and formulating anticancer drugs into nanomedicines also helps overcome chemoresistance. In this review, we briefly describe the different classes of cancer chemotherapeutic agents, their mechanisms of action and resistance, and evidence of overcoming the resistance using nanomedicines. We then emphasize on gemcitabine and our experience in discovering the unique (stearoyl) gemcitabine solid lipid nanoparticles that are effective against tumor cells resistant to gemcitabine and elucidate the underlying mechanisms. It seems that lysosomes, which are an obstacle in the delivery of many drugs, are actually beneficial for our (stearoyl) gemcitabine solid lipid nanoparticles to overcome tumor cell resistance to gemcitabine.

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Synthesis and in vitro evaluation of novel lipophilic monophosphorylated gemcitabine derivatives and their nanoparticles

Cited by 43 publications

References 41 publications

Comparison of in vitro dialysis release methods of loperamide-encapsulated liposomal gel for topical drug delivery

Comparison of in vitro dialysis release methods of loperamide-encapsulated liposomal gel for topical drug delivery

Development and in vitro evaluations of new decitabine nanocarriers for the treatment of acute myeloid leukemia

Overcoming tumor cell chemoresistance using nanoparticles: lysosomes are beneficial for (stearoyl) gemcitabine-incorporated solid lipid nanoparticles

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