Project aims and the underpinning science:

We seek to develop an insert into a breast shield that substantially inactivates HIV in breast milk throughout the daily feeding of an infant. HIV infects about 15% of infants through breastfeeding from a HIV+ mother (UNAids, 2001). The use of formula milk in low-resource settings causes even more deaths, due to diarrhea and malnutrition (WHO, 2008).  Giving anti-retroviral drugs to infants can protect them from HIV infection, but raises other safety issues (Gray et al., 2008).  Mothers need a way to protect babies from HIV in breast milk that is practical and allows normal breastfeeding.  In a different setting, the technology might also be used as an alternative means for single and multiple drug delivery to infants, for example nutrients such as vitamin D in the UK (NHS, 2008) or iron in Africa (Stoltzfus, 2003). These can be difficult to administer using normal routes (i.e. pills). The device could also be helpful for medicines that are currently administered as syrups to infants, also often requiring refrigeration (Milne et al., 2008, Breitkreutz, 2008).

 

Research approach

The concept involves impregnating the surfaces of an insert placed in the nipple of the breast shield with an anti-viral agent that is released into milk during the breast feeding of infants.  The technical challenge is to load the surface of the insert with a low-cost anti-viral agent that is desorbed under the pertaining flow conditions of milk at such a rate that an adequate dose can be delivered to the child during feeding.  This involves various considerations:

1.      HIV inactivation

A number of potential anti-viral agents are being investigated. Of these, surfactants are known to disrupt the lipid envelope of retroviruses and render them non-infectious and sodium dodecyl sulphate (SDS) has been shown to rapidly inactivate HIV in breast milk in vitro at levels that are non-toxic to infants (Urdaneta et al., 2006).  Copper oxide filters and impregnated fibers can also effectively inactivate HIV (Borkow et al., 2008) and should be tested on infected milk. 

Another type of potential agent is the “Klibanov coating”; a non-leaching, permanent microbicidal polymeric coating (Klibanov, 2007).  Coatings of this type, comprising hydrophobic polycations, can be covalently attached to the surface of the textile material, and would provide a large surface area for microbicidal action.  However, SDS offers the most promising approach as it would travel with the milk into the infant’s gastrointestinal tract and hence provide a long residence time for viral inactivation (SDS is a safe food ingredient).  Copper oxide and the Klibanov coating interaction with milk remain in the filter and contact times are much lower. Other SDS-like compounds and combinations with the aforementioned technologies could also be considered.  

A method to supply a sustained release of SDS from an insert must be devised and samples virologically tested. Initially this will be in the Cambridge University Chemical and Biotechnology Department where model HIV virus is already studied. Finalized designs would be virologically tested . Measured rates of release of SDS and a hydrophobic dye (an easily measured drug mimic) into deionized water with the compounds applied onto several types of non-woven fiber.  To ensure that all milk is treated throughout the day with sufficient SDS, there must be a sustained release of the agent as milk passes through the insert, and it would most probably be necessary to replace the insert daily. However, the delayed release in preliminary 'proof-of-concept' experiments needs further study to optimize and understand how it works. Specifically, SDS is still not released at high enough concentrations or for long enough. Also a “tea bag” insert into the breast shield is another potential design and a color change system to show when an insert is used up would be devised.

 

2.      Controlled release

The release of drugs from a replaceable non-woven fiber insert inside the shield will be studied. Controlled release has been studied extensively in matrix tablets, and also in thin film dosage forms. However, coatings  plus drug onto non-woven fabrics is a novel drug formulation, and requires characterization and optimization (since the release rate of drug by diffusion will vary with the thickness of the control layer).  It is planned to transfer the published understanding about the mechanism of delayed release,to engineer a filter that has a controlled release of drugs under flow conditions.

References:

Borkow, G., Lara, H. H., Covington, C. Y., Nyamathi, A., Gabbay, J.,  2008. Deactivation of Human Immunodeficiency Virus Type 1 in Medium by Copper Oxide-Containing Filters. Antimicrobial Agents and Chemotherapy 52 (2): 518-525

 

Breitkreutz, J., 2008. European perspectives on pediatric formulations. Clin Ther. Nov 30 (11):2146-54

 

Gray R. H., Brahmbhatt, H., 2003. Child mortality associated with reasons for non-breastfeeding and weaning: is breastfeeding best for HIV-positive mothers? J. AIDS, 17: 879-88

 

Klibanov, A. M., 2007. Permanently microbicidal material coatings. J. Mater. Chem., 17: 2479-2482

 

Milne, C. P., Bruss, J. B., The economics of pediatric formulation development for off-patient drugs.  Clin ther. Nov 30(11):2133-45

 

National Health Service (NHS), 2008. Vitamin supplement recommendations. http://www.healthystart.nhs.uk/en/fe/page.asp?n1=1&n2=8&n3=97&n4=100

 

Stoltzfus, R. J., 2003. Iron deficiency: global prevalence and consequences. Food Nutr. Bull. Dec; 24(4 Suppl):S99-103

 

Urdaneta-Hartmann, S. et al., 2006. Biochemical Analysis of Human Milk Treated With Sodium Dodecyl Sulfate, an Alkyl Sulfate Microbicide. That Inactivates Human Immunodeficiency Virus Type 1. J Hum Lact, 22 (61): 61-74.

 

UNAIDS, 2001. HIV and Infant Feeding. UNAIDS, http://data.unaids.org/Publications/IRC-pub01/jc180-hiv-infantfeeding_en.pdf

 

World Health Organization (WHO), 2008. Conclusions and recommendations regarding infant feeding. https://www.who.int/reproductivehealth/publications/new_data_ prevention_mtct_hiv /infant_feeding.en.html