Efficient Intraliposomal Encapsulation of Cancer Drugs
Efficient Intraliposomal Encapsulation of Cancer Drugs
A counter-intuitive and highly efficient method for encapsulating challenging drug chemotypes.By reversing the conventional direction of pH gradients, optimizing internal buffer composition and modifying temperatures, a process that was grossly inefficien
San Diego, CA, United States
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Background

Liposomal carriers are hollow spherical structures that have been widely used to improve the delivery, extend the circulation time and decrease the toxicity of a number of drugs in development and approved for human use. However, many drug chemotypes are inefficiently loaded. One such chemotype includes drugs that cannot be readily dissolved in water. These 'hydrophobic' compounds require suspension in detergents for ultimate incorporation into the wall of the liposome, which greatly limits the loading capacity. In order to gain access to the vastly superior capacity of the hollow internal cavity of the liposome, UC researchers have developed a counter-intuitive and highly efficient method for encapsulating challenging drug chemotypes.


Technology Description

Because standard liposomal remote loading methods, which had been developed to encapsulate doxorubicin and camptothecin analogues, limited the potential of highly hydrophobic drug chemotypes, UC researchers revisited the basics of the liposomal equation. By reversing the conventional direction of pH gradients, optimizing internal buffer composition and modifying temperatures, a process that was grossly inefficient has been converted to one that can be applied for commercial development. 


Applications

  • May rescue hydrophobic drugs that suffer from poor pharmacokinetics and limited feasibility for manufacturing and development
  • May improve the profile and extend the market life of drugs that are already approved for human use.

 

Advantages

  • Specified conditions are easily controlled in commercial settings.
  • Though specifically validated for staurosporine and hydrophobic drugs, the approach may also be useful for other chemotypes that do not efficiently load into current liposomal delivery vehicles.

 

State Of Development

In vivo studies of antitumor efficacy in a murine tumor xenograft model (low dose encapsulated staurosporine vs. drug) were supported by earlier proof of concept studies. The loading efficiency of staurosporine (as a prototypic hydrophobic drug) was optimized with regard to pH gradient, buffer, temperature and drug:lipid ratio. Similar experiments with pitivastatin, dasatinib, and imatinib have confirmed a more broad utility and have also demonstrated good retention of drug when incubated in the presence of human serum. In vitro cytotoxicity was assessed in an MTT Cell viability assay.


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