University of Texas System

Other

Insmed Incorporated

Yiyu Zou

Roman Perez-Soler

Waldemar Priebe

Vladimir Malinin

Walter Perkins

Jin K Lee

Frank G Pilkiewicz

One aspect of the invention relates to methods of treating cancer in a patient comprising administering intraperitoneally to a patient in need thereof a cancer treating effective amount of a composition comprising a lipid-complexed platinum compound wherein the concentration of the platinum compound of the lipid-complexed platinum compound composition is greater than about 1.2 mg/ml. Another aspect of the invention relates to lipid-complexed platinum compound compositions where the concentration of the platinum compound is greater than about 1.2 mg/ml.

Methods of treating cancer with high potency lipid-based platinum compound formulations administered intraperitoneally

This invention provides an aqueous/t-butanol solvent-system, facile reconstitute, submicron-reconsitiute preliposome-lyophilaye and method of its preparation and use. In one embodiment this entails a modified method for the preparation of a submicron and stable liposome formulation of the non-cross-resistant anthracycline Annamycin is described. The optimal lipid composition was DMPC:DMPG at a 7:3 molar ratio and the optimal lipid:drug weight ratio 50:1. The selected formulation is a preliposome lyophilized powder that contains the phospholipids, Annamycin, and 1.7 mg Tween 20 per mg of Annamycin. The liposome suspension is obtained on the day of use by adding normal saline at 37&#xb0; C. (1 ml per mg Annamycin) and hand-shaking for one minute. The presence of Tween 20 is essential in shortening the reconstitution step (from &#x3e;2 hours to 1 minute), avoiding the early formation of free drug crystals, and reducing the median particle size (from 1.5 &#x3bc;m to 0.15-0.20 &#x3bc;m) without destruction of the liposome vesicles. The chemical stability of the preliposome powder at room temperature was &#x3e;3 months and the chemical and physical stability of the liposome suspension at room temperature &#x3e;24 hours. The in vitro cytotoxicity of the formulation was equivalent to that prepared by the standard evaporation method. The results of the study indicate that small amounts of surfactant may be used to enhance the reconstitution step and reduce the liposome size of lyophilized liposome formulations of lipophilic drugs.

Submicron liposome suspensions obtained from preliposome lyophilizates

The present invention provides a pharmaceutical composition, comprising: (a) cationic lipids, wherein said lipids are a liposomal mixture of a diacyl-ethyl-phosphocholine and 1,2-diacyl-sn-glycero-3-phosphoethanolamine; and (b) a plasmid cDNA sequence encoding a protein having tumor suppressor or pro-apoptotic activity. This composition has a high gene transfection efficiency at non-toxic doses and is designed to transfect human bronchial premalignant lesions and early endo-bronchial malignancies. Also provided is a method of method of treating a cancerous or pre-cancerous condition of the respiratory tract in an individual in need of such treatment, comprising the step of administering to said individual a pharmacologically effective dose of a pharmaceutical composition, comprising: (a) cationic lipids, wherein said lipids are a liposomal mixture of a diacyl-ethyl-phosphocholine and 1,2-diacyl-sn-glycero-3-phosphoethanolamine; and (b) a plasmid cDNA sequence encoding a protein having tumor suppressor or pro-apoptotic activity.

Gene therapy of tumors using non-viral delivery system

This invention provides an aqueous/t-butanol solvent-system, facile reconstitute, submicron-reconsitiute preliposome-lyophilaye and method of its preparation and use. In one embodiment this entails a modified method for the preparation of a submicron and stable liposome formulation of the non-cross-resistant anthracycline Annamycin is described. The optimal lipid composition was DMPC:DMPG at a 7:3 molar ratio and the optimal lipid:drug weight ratio 50:1. The selected formulation is a preliposome lyophilized powder that contains the phospholipids, Annamycin, and 1.7 mg Tween 20 per mg of Annamycin. The liposome suspension is obtained on the day of use by adding normal saline at 37.degree. C. (1 ml per mg Annamycin) and hand-shaking for one minute. The presence of Tween 20 is essential in shortening the reconstitution step (from &gt;2 hours to 1 minute), avoiding the early formation of free drug crystals, and reducing the median particle size (from 1.5 .mu.m to 0.15-0.20 .mu.m) without destruction of the liposome vesicles. The chemical stability of the preliposome powder at room temperature was &gt;3 months and the chemical and physical stability of the liposome suspension at room temperature &gt;24 hours. The in vitro cytotoxicity of the formulation was equivalent to that prepared by the standard evaporation method. The results of the study indicate that small amounts of surfactant may be used to enhance the reconstitution step and reduce the liposome size of lyophilized liposome formulations of lipophilic drugs.

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Houston, TX, United States of America

Yiyu Zou