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Multipurpose gel formulations containing antiretroviral-loaded lactoferrin nanoparticles and antibiotics for combination HIV prevention and treatment of bacterial vaginosis

School of Pharmacy | PHD
Funding
Funded
Reference Number
PMY/2251/KM3
Application Deadline
31 January 2025
Start Date
1 October 2025

Overview

This is an exemplar PhD project co-supervised by Dr. Sheiliza Carmali (School of Pharmacy) and Prof. Karl Malcolm (School or Pharmacy). No funding has yet been secured for the project. We particularly welcome applications from students (including international students) who are willing and able to self-fund their PhD, UK/EU applicants for DfE studentship application. Lactoferrin Lactoferrin is a multifunctional globular protein. As a component of the body’s immune system, it has broad-spectrum antimicrobial activity and is produced in various body fluids, including vaginal fluid. Its antibacterial activity is due to its ability to (i) sequester free iron, an essential substrate for bacterial growth, and (ii) bind to lipopolysaccharide of bacterial walls (the oxidized iron component of the lactoferrin oxidizes bacteria via formation of peroxides, thereby lysing the cell). It has also been shown to be active against human immunodeficiency virus (HIV) and herpes simplex virus (HSV). Lactoferrin is also a prebiotic, stimulating the growth of certain healthy bacteria. Bacterial vaginosis Bacterial vaginosis is a very common condition associated with bacterial imbalance in the vaginal microbiota (loss of healthy lactobacillus; overgrowth of facultative anaerobic bacteria, such as Gardnerella vaginalis). It affects about 40–50% of women globally. Following treatment with conventional antibiotics, long-term recurrence rates for bacterial vaginosis remain very high. Lactoferrin has been proposed and tested as an alternative, non-antibiotic, treatment option for BV. Bacterial vaginosis and HIV/STIs Bacterial vaginosis increases the risk of sexual acquisition of HIV and other sexually transmitted infections, including herpes simplex virus (HSV), human papillomavirus (HPV), chlamydia and gonorrhea.

Application
This PhD project will focus on developing a multipurpose vaginal gel formulation to simultaneously prevent HIV infection and treat bacterial vaginosis. Dapivirine—a non-nucleoside reverse transcriptase inhibitor that has recently been approved in a vaginal ring formulation for HIV prevention—will be formulated in lactoferrin nanoparticles. The dapivirine-loaded nanoparticles and a conventional BV antibiotic (such as metronidazole or clindamycin) will then be formulated in an aqueous vaginal gel (carbomer or hydroxyethylcellulose). This part of the project will involve various aspects of pharmaceutical formulation and analysis, including HPLC method development for drug quantification, rheological testing, dissolution/in vitro release testing, microbiological testing, etc.
HIV-1 entry into hosts cells is driven by electrostatic interactions. To enhance lactoferrin targetability and improve HIV-1 inhibitory activity, lactoferrin surface modifications with ligands containing sulfonate or phosphonate groups will be investigated. Lactoferrin nanoparticles will be prepared using sol-oil chemistry and their physical properties characterized by a range of techniques including microscopy, dynamic light scattering, fourier-transform infrared spectroscopy and HPLC. Raman spectroscopy will be used to confirm ligand conjugation. The developed lactoferrin nanoparticles will be biologically evaluated in vitro, such as cellular localization and competitive binding assays along with toxicity studies and antiviral activity studies.
The successful candidate will be part of a highly interdisciplinary project and will learn about nanoparticle preparation, bioconjugation, gel formulation and biological testing.

We will consider UK/EU for DfE studentship, Chinese applicants with a Masters degree for the CSC (China Scholarship Council)-QUB co-funded studentship and worldwide applications for self-funded projects.

Funding Information

DfE Applications deadline 31st January 2025

Applications considered throughout the year from applicants who have secured external funding or are willing to self-fund the project.

Project Summary
Supervisor

Professor Karl Malcolm...

Research Profile

Dr. Sheiliza Carmali – School of Pharmacy
Prof. Karl Malcolm – School of Pharmacy


Funding Body
Department for Economy
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