Antitumor effect of liposome-incorporated camptothecin in human malignant xenografts

Daoud, Sayed S.; Fetouh, Mohamed I.; Giovanella, Beppino C.

doi:10.1097/00001813-199502000-00010

Cited by 47 publications

(15 citation statements)

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“…[3][4][5] Most of the research works were focused on the particulate delivery of the CPT and its analogues especially as liposomes and nanoparticles. [6][7][8][9][10][11] Very few reports were published on the delivery of CPT and its analogues by oral matrix tablet technology. 12,13 In the present study, we aim at developing prototype CR matrix tablets of CPT keeping in view of its shorter elimination half life.…”

Section: Introductionmentioning

confidence: 99%

Studies on Development of Controlled Release Matrix Tablets of Camptothecin-An Anticancer Drug

Nalluri¹,

Devineni²,

Male³

et al. 2015

IJPER

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Objectives: The present investigation was carried out with an objective of formulating prototype controlled release (CR) matrix tablets of Camptothecin (CPT), an anti-cancer drug. Experimental: pH solubility profile studies of CPT and solubility of CPT in different surfactants were carried out. Controlled release tablets were prepared by direct compression method using hydroxyl propylmethyl cellulose (HPMC LVCR and HPMC K4M) as release retardants. The effect of different grades of microcrystalline cellulose (MCC) like Avicel PH 101 and Avicel PH 105 and solubilizing agents like cyclodextrins were included in the formulations and their effect on CPT release from tablets were studied. Results and Discussion: Solubility studies were conducted in order to select suitable dissolution medium for CPT. Based on the solubility studies, 0.1N HCl with 3% w/v SLS (pH1.2) was selected as dissolution medium. The FTIR and DSC results indicated that there was no in situ interaction between CPT and the selected excipients in the formualtions. Formulations containing 20% w/w of hydroxypropyl-β-cyclodextrin with Avicel PH105 as filler and HPMC k4M as release retardant gave superior CPT release of 98.40 ± 1.02% at the end of 12 h and fulfilled the regulatory requirements. The Higuchi square root model showed higher correlation coefficient values (0.949-0.990) indicating diffusion was the release mechanism for CPT from tablets. Conclusion: CPT can be formulated in to CR matrix tablets using HPMC K4M as release retardant and MCC as filler for better therapeutic efficacy.

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Section: Introductionmentioning

confidence: 99%

Studies on Development of Controlled Release Matrix Tablets of Camptothecin-An Anticancer Drug

Nalluri¹,

Devineni²,

Male³

et al. 2015

IJPER

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“…In addition to the synthesis of new derivatives and pro-drug products, 6-10) the development of adequate drug carriers is gaining increasing attention. There are many reports about effective formulation and utilization of CPT in cancer therapy by using drug delivery technologies such as liposomes, 11,12) microemulsions, 12) microspheres, 13,14) and inclusion complexes with cyclodextrins. 15) Previously we have reported that the stability of CPT loaded polymeric micelles in vivo was increased by benzyl esterification of hydrophobic segment of block copolymer.…”

Section: )mentioning

confidence: 99%

Artificial Lipids Stabilized Camptothecin Incorporated in Liposomes

Maitani

Katayama

Kawano

et al. 2008

Biological & Pharmaceutical Bulletin

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Camptothecin (CPT) is a naturally occurring cytotoxic alkaloid isolated from the Chinese plant Camptotheca accuminate.1) CPT and some of its analogs have shown a broad spectrum of antitumor activity against many solid tumors in xenografts including colorectal cancer. 2,3) CPT inhibits the enzyme DNA topoisomerase I, initially by noncovalent binding and subsequently by stabilization of the complex through a nucleophilic attack by the enzyme at the acyl position of the CPT lactone ring. 4)Of significant importance for pharmaceutical formulation is that, while only the lactone form of CPT is biologically active, this form exhibits poor aqueous solubility. The lactone of CPT is converted to carboxylate in a pH-dependent equilibrium.5) To overcome the aforementioned solubility problems and hydrolytic processes of CPT, several approaches have been investigated. Numerous attempts have been made to prepare water-soluble CPT analogs. The majority of these analogs were less potent in assays both in vitro and in vivo than the parent drug. In addition to the synthesis of new derivatives and pro-drug products, 6-10) the development of adequate drug carriers is gaining increasing attention. There are many reports about effective formulation and utilization of CPT in cancer therapy by using drug delivery technologies such as liposomes, 11,12) microemulsions, 12) microspheres, 13,14) and inclusion complexes with cyclodextrins. 15) Previously we have reported that the stability of CPT loaded polymeric micelles in vivo was increased by benzyl esterification of hydrophobic segment of block copolymer. [16][17][18] However, long circulation of CPT loaded polymeric micelles in vivo was not achieved yet. Other carriers such as liposomes were examined because release of drugs encapsulated in carriers depended on carriers. The designed amphipathic compounds are called artificial lipid, which has similar properties with phospholipid to form vesicles. Therefore, artificial lipid with a phenyl group, e.g., 3,5-bis(dodecyloxy)benzoic acid, was synthesized and added to the liposome formulation. The PEGylated liposomes incorporating CPT were stable in vivo. 19) However, there was not enough information about interaction between CPT and artificial lipid molecules in liposomes.To develop the therapeutic utilization of CPT, it is necessary to prepare liposomes with high incorporation efficiency and stability of CPT. This study demonstrated that incorporation of 5 mol% of 3,4,5-tris(dodecyloxy)benzoic acid increased incorporation efficiency and stability of CPT in liposomes. MATERIALS AND METHODSMaterials (S)-(ϩ)-Camptothecin (CPT), cholesterol (Ch), high performance liquid chromatography (HPLC) grade methanol and tetrahydrofuran (THF) were purchased from Wako Pure Chemicals (Tokyo, Japan). Hydrogenated soybean phosphatidylcholine (HSPC, Ͼ90% phosphatidylcholine), and oleic acid (OA) were purchased from NOF Corporation (Tokyo, Japan). 4-n-Dodecyloxy benzoic acid (M12B) was purchased from Tokyo Chemical Industry (Tokyo, Japan). 3,5-Bis(dodecyloxy)...

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“…Release studies of liposomal 20-S-CPT show an initial rapid 50% loss of the drug in 4 h, followed by a slow leakage of the remaining drug over a period of 20 h. Complete tumour regression occurred after a single i.m. injection of this formulation at 10 mg kg-1 in nude mice xenografted with CLO breast carcinoma or BRO melanoma, with minimal host toxicity (Daoud et al, 1995).…”

Section: Preclinical Studiesmentioning

confidence: 99%

Topoisomerase I inhibitors: the relevance of prolonged exposure for present clinical development

Gerrits

Jonge²,

Schellens³

et al. 1997

Br J Cancer

113

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Summary Topoisomerase inhibitors constitute a new class of anti-cancer agents. Recently, topotecan and irinotecan were registered for clinical use in ovarian cancer and colorectal cancer respectively. Cytotoxicity of topoisomerase inhibitors is S-phase specific, and in vitro and in vivo studies have suggested that, for efficacy, prolonged exposure might be more important than short-term exposure to high concentration. Clinical development of those topoisomerase inhibitors that have reached this stage is also focused on schedules aiming to achieve prolonged exposure. In this review, we summarize all published preclinical studies on this topic for topoisomerase inhibitors in clinical development, namely 20-S-camptothecin, 9-nitro-camptothecin, 9-amino-camptothecin, topotecan, irinotecan and G1147211. In addition, preliminary data on clinical studies concerning this topic are also reviewed. The data suggest that prolonged exposure may indeed be relevant for anti-tumour activity. However, the optimal schedule is yet to be determined. Finally, clinical data are yet too immature to draw definitive conclusions.

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Antitumor effect of liposome-incorporated camptothecin in human malignant xenografts

Cited by 47 publications

References 0 publications

Studies on Development of Controlled Release Matrix Tablets of Camptothecin-An Anticancer Drug

Studies on Development of Controlled Release Matrix Tablets of Camptothecin-An Anticancer Drug

Artificial Lipids Stabilized Camptothecin Incorporated in Liposomes

Topoisomerase I inhibitors: the relevance of prolonged exposure for present clinical development

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