A novel method of altering a protein
in milk to bind with an antiretroviral drug promises to greatly improve
treatment for infants and young children suffering from HIV/AIDS, according to
a researcher in Penn State's College of Agricultural Sciences.
That's
critical because an estimated 3.4 million children are living with HIV/AIDS,
the World Health Organization reports, and nine out of 10 of them live in
resource-limited countries in sub-Saharan Africa, where effective
antiretroviral treatments still are not widely accessible or available.
International medical experts believe less than a third of affected children
worldwide receive an antiretroviral drug.
Complicating
treatment is that most antiretroviral drugs are not well tolerated by very
young children. One of the most commonly prescribed antiretroviral drugs for
treating and preventing HIV infection, Ritonavir, has undesirable side effects
and important oral-delivery problems. Its physicochemical properties challenge
its administration to infants, explained Federico Harte, associate professor of
food science.
"Ritonavir
has a high hydrophobicity and low solubility in water, which lead to a low
dissolution rate in the gastrointestinal fluid and, hence, to insufficient
bioavailability. The liquid formulation used to treat infants over one month of
age contains 43 percent ethanol and has an awful flavor that has been described
as bitter-metallic, medicinal, astringent, sour and burning," he said.
"Moreover,
when coming into contact with the stomach mucosa, Ritonavir causes nausea,
vomiting and diarrhea. Therefore, we need to develop alternative pediatric
formulations of Ritonavir and overcome its poor water solubility to improve its
oral administration to infants and children."
To
solve that problem, Harte looked to a group of proteins in cow's milk celled
caseins. Casein proteins form spherical aggregates called casein micelles,
which are responsible, incidentally, for the white color of milk. The casein
micelles in mammals' milk are natural delivery systems for amino acids and
calcium from mother to young, and Harte reasoned, might deliver Ritonavir
molecules as well.
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Altered milk protein can deliver aids drug to
infants
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"He
have been working with bovine casein micelles for a few years now, and we have
investigated the structure and functionality of these proteins. "What he
found is these micelles are able to carry molecules that have very little
solubility in water, that have low molecular weight and that are very
hydrophobic -- such as Ritonavir."
Significantly,
Harte discovered in his research recently published online in the Journal of Pharmaceutical Research that subjecting milk to
ultrahigh-pressure homogenization enhances the binding properties of the casein
micelles. Normal milk is homogenized at 10 to 15 megapascals, he pointed out.
Milk in this research was homogenized at between 400 and 500 megapascals,
disassociating the casein micelles and improving the protein's binding
qualities to attach to drug molecules.
"As
a result of this enhanced binding of molecules, they believe a milk powder
containing Ritonavir can be used as baby formula, providing a transport system
for a drug that is not very soluble in water.
Posted By:-
Biotechnology Department
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