By Dr Tony Curtis (Senior Lecturer in Organic and Medicinal Chemistry , Institute for Science & Technology in Medicine, Keele University)
The great solubility challenge
Investigating potential in targeted drug delivery
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Hydrophobic molecules have very low solubility in water
which is highly undesirable for drugs which must enter
the circulation. Over the past few decades, the development of new drug delivery systems to overcome the insolubility of hydrophobic drugs (drugs that seemingly repel
water as they have no attraction to it) has attracted much
attention among researchers in the pharmaceutical arena. Since approximately 60% of therapeutic agents identified in screening programs are classified as hydrophobic
there is a great need to provide sufficient formulation
strategies in order to aid the drug development pipeline. It
is well recognised that many of the ingredients commonly
used in drug formulation possess undesirable properties
in terms of their viscosity, efficiency and stability in aqueous systems such as blood plasma. Hence, novel technologies which can increase the solubility of drug molecules in aqueous media and overcome the issues of traditional excipients are required.
Diagram showing drug encapsulation inside a soap-like molecule
aiding water solubility
work is ongoing to investigate their potential in cancer therapy and ‘smart’
drug delivery systems.
The Keele Nanopharmaceutics group work on multiple
approaches to such challenges and have developed a
range of both amphiphilic polymers and calixarenes capable of enhancing drug solubility to a high degree. Amphiphilic polymers are entities composing of a water
‘loving’ molecule coupled with a water ‘hating’ molecule.
When the polymers are placed into aqueous environments they spontaneously aggregate into core-shell
structures in which the polymers form a shell around an
empty core. These structures are capable of housing insoluble drug molecules. The polymers developed have
shown to act as universal drug solubility agents and work
is ongoing to investigate their potential in cancer therapy
and ‘smart’ drug delivery systems in which the drug is
released in response to a trigger such as heat.
Calixarenes are a family of organic compounds, which
possess characteristic three-dimensional structures. Calixarenes form cup-like structures with well-defined upper
and lower rims containing a central cavity in both the solid state and in solution. They possess a hydrophobic interior space which can accommodate or host organic molecules as guests in so-called host-guest interaction. Calixarenes enhance the solubility of hydrophobic drugs via
such host-guest interactions. The calixarenes developed
can change their structure in different solvents and at
increased temperature. The Keele Nanopharmaceutics
group at ISTM have modified the molecular properties of
calixarenes by adding various groups onto both the upper
and lower rims of the structures to enhance their solubility
in water. These are now being investigated for their potential in targeted drug delivery.
NANOPHARMACEUTICS
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