Project Details
Description
Amphotericin B (AmB) is a first option therapy against life-threatening invasive fungal infections. However, as of
now administration of AmB is limited to intravenous infusions because of poor solubility and poor permeability,
which severely impacts patient accessibility. Although oral AmB medication is a highly sought-after resolution,
oral AmB formulations have yet not to be achieved even after 6 decades of commercialization. Our lab has
discovered novel stable binary lipid systems (BLS) that consist of one lipid and one water-soluble surfactant to
enhance oral bioavailability of water insoluble drugs. In 2020, we were awarded a Maximizing Investigators’
Research Award (R35) from NIGMS to further study this new formulation technology. The goal of the parent R35
grant is to develop a novel formulation technology by bringing our unique findings of new colloidal BLS into solid
dosage forms to improve oral absorption of insoluble drugs. One of studies in the parent grant is to build a library
of stable BLS using lipids and traditional surfactants. AmB represents a type of amphiphilic molecules that have
big ring structure with both hydrophobic and hydrophilic regions. The traditional surfactants with a polar head
group conjugated to non-polar tails are not suitable for AmB. Bile salts are desirable biosurfactants due to their
biocompatibility and unique structure with planar steroidal moiety. A commercial AmB injection is made of bile
salt micelles. However, bile salts have not been used in oral solid dosage forms because they are water-soluble
and normally do not like lipids. With our novel findings in the BLS, we hypothesize that the BLS containing bile
salts is an effective formulation strategy to enhance oral absorption of AmB. Thus, the goal of this Diversity
Supplement is to develop novel oral granules for AmB by using BLS containing one lipid and one bile salt as well
as train an African American PhD student to become a biomedical researcher. We will develop oral AmB granules
and evaluate pharmacokinetics and tissue distribution. We anticipate the outcome of the Supplement will
establish bile salt based BLS, which will be incorporated into the parent questionnaire to expand the library and
test our new formulation technology. This proposed Diversity Supplement will support an African American PhD
student for his dissertation research. The proposed research plan aligns with the candidate’s long-term career
goals and individual development plan (IDP). The principal investigator/mentor has extensive mentoring
experiences, especially for underrepresented students. This project has been designed around improving the
candidate’s skills, as per the candidate’s IDP, as well as training the candidate to be able to take the next steps
along the path of an independent pharmaceutical scientist. The proposed training plan and specific aims outline
a path for structured learning of new pharmaceutical techniques, conceptual discipline specific knowledge,
experimental design, data analysis and also account for great opportunities to grow in terms of presentation,
writing and leadership skills. In all, this project is well designed to enhance the parent grant in addition to
bolstering the candidate’s capability and skills in preparation for future research grant and career development.
Status | Finished |
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Effective start/end date | 1/07/20 → 30/06/23 |
Funding
- National Institute of General Medical Sciences: $751,817.00
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