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Compositions and methods for hydrophobic drug delivery

A composition and hydrophobic technology, applied in drug combination, drug delivery, pharmaceutical formulation, etc., can solve the problem that it is difficult to achieve a predetermined drug concentration into the liposome compartment

Inactive Publication Date: 2006-09-27
PRO PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, these formulations suffer from the fact that it is difficult to achieve a predetermined drug concentration into the liposomal compartment

Method used

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  • Compositions and methods for hydrophobic drug delivery
  • Compositions and methods for hydrophobic drug delivery
  • Compositions and methods for hydrophobic drug delivery

Examples

Experimental program
Comparison scheme
Effect test

Embodiment A

[0072] COLO 205 Human Colon Cancer In Vivo Study: The response of subcutaneously implanted COLO 205 human colon tumors to combined treatment with the cytotoxic chemotherapeutic agent paclitaxel and modified galactomannan was evaluated in male NCr-nu athymic nude mice. See image 3 .

[0073] One week prior to the experiment, male NCr-nu athymic nude mice (Frederick Cancer Research and Development Center, Frederick, MD) were acclimatized in the laboratory. Animals were housed in microisolator cages, five per cage, on a 12-h day / night cycle. Animals received filtered water and sterile rodent chow ad libitum. Animals were observed daily and clinical signs were recorded. On study day 13, the first day of treatment initiation, animal weights ranged from 25-34 g. Mice were healthy and had not previously been used in other experimental procedures.

[0074] Thirty to forty mg COLO 205 human colon tumor specimens were implanted subcutaneously (S.C.) using a 12-gauge trocar into mic...

Embodiment B

[0078] In Vitro Study of HT-29 Human Colon Carcinoma: This experiment was performed using the 96-well plate method. Paclitaxel (Sigma, USA) was first dissolved in ethanol as a 10 mg / mL solution, and then a 10 mg / mL modified alkylgalactogalactan solution (from fermented meat of Acinetobacter calcoaceticus (PETROFERM, INC, FL.) Purified from coarse powder prepared in soup) emulsified at a ratio of 1:9. Suspensions were serially diluted in saline and added to growth medium in 96-well plates. Each vial was seeded with a suspension of HT-29 human tumor cells (approximately 1000 to 10000 cells / well). Incubate at 37°C for 48 to 72 hours and observe at optical density at 490 nm. Control wells (no drug) were read at approximately 1.500 optical units, while 100% inhibition was read at 0.500 optical units (0.01 μg / mL of h-TNF (Tumor Necrosis Factor) was used as a positive control). Calculate LD at less than 10 ng paclitaxel per mL 50 . 100% cytotoxic effect at 50 to 100 ng / ml.

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Abstract

Disclosed herein are compositions and methods for the delivery and targeting of therapeutics using nanometer sized polysaccharide structures. The methods and compositions described herein afford improved efficacy for pharmaceuticals such as anti-tumor drugs on metastatic tumor. The methods described herein are applicable to all chemotherapeutic agents and are especially useful for poorly soluble (hydrophobic) drugs which when formulated with the present compositions render them deliverable in physiological fluids. The methods and compositions described herein also improve the efficacy of pharmaceutical agents by targeting carbohydrate receptors specific to tumors that mediate endocytosis or enhance delivery of the drug to the ultimate site of action.

Description

[0001] related application [0002] This application claims priority to and benefit of US Provisional Application 60 / 486,338, filed July 11,2003. technical field [0003] The present invention relates to methods and compositions for drug delivery. In particular, the present invention relates to methods and compositions for the delivery of agents with low solubility constants, especially in physiological fluids. Background technique [0004] In an attempt to increase efficacy and / or reduce toxicity, chemotherapeutic agents have been targeted to tumor cells using so-called drug targeting techniques. Effective drug targeting often improves the method of drug administration. Products utilizing drug delivery technologies are generally considered new. Safety and efficacy are improved by using drug targeting to control drug concentrations in the blood. The ultimate criterion for effective drug delivery is undoubtedly controlled and optimized targeting or increased drug localiza...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/00A61KA61K31/715
CPCA61K9/0019A61K9/5161A61K9/1075A61P35/00
Inventor D·普拉特E·佐莫A·科尔约瑟夫
Owner PRO PHARMA