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

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.

Applicants should have a 1st or high 2.1 honours degree (or equivalent) in a relevant subject. Relevant subjects include Pharmacy, Pharmaceutical Sciences, Biochemistry, Biological/Biomedical Sciences, Chemistry, Engineering, Biomedical Engineering or a related discipline. Students who have a 2.2 honours degree and a Masters degree may also be considered, but the University reserves the right to shortlist for interview only those applicants who have demonstrated high academic attainment to date.

Postgraduate Research applicants must have applied to Queen’s, via the Direct Applications Portal 

https://dap.qub.ac.uk/portal/user/u_login.php

Please note that applicants do not need to draft a detailed research proposal. Instead, applicants can simply copy and paste the summary descriptive text provided above. However, you may wish to elaborate further on the concept, particularly if you have other ideas around the general topic.

This project has not yet secured an external source of funding. Before making an application, students should therefore ensure they have identified a viable funding source to support their postgraduate studies. Self-funding international applicants are particularly encouraged to apply.

Funded PhD studentships available in the School of Pharmacy, Queen's University Belfast

http://www.qub.ac.uk/schools/SchoolofPharmacy/Research/PostgraduatePositions/ 

Research at the School of Pharmacy, Queen's University Belfast

http://www.qub.ac.uk/schools/SchoolofPharmacy/Research/

Dr. Sheiliza Carmali’s research homepage

https://pure.qub.ac.uk/en/persons/sheiliza-carmali

Prof. Karl Malcolm’s research homepage

https://pure.qub.ac.uk/en/persons/karl-malcolm

The project will provide extensive training and skills development for the student in the following topics:

·        Preparation and characterisaton of drug-loaded nanoparticles

·        Gel formulation

·        Drug product testing and analysis (e.g. HPLC; dissolution/release; thermal analysis; particle size measurement; rheology; etc.

Multipurpose prevention technologies (MPTs) are an emerging class of biomedical interventions intended to prevent at least two sexual and reproductive health issues simultaneously – unintended pregnancy, STIs, and HIV infection. MPTs may be particularly important in situations where individuals face multiple health risks but have limited access to healthcare resources. While MPTs hold great promise, there are many challenges ahead associated with their development and implementation—scientific and technical, regulatory and approval, user acceptance and adherence, funding and resource allocation, marketing and distribution, ethical and equity considerations, education and awareness, and integration into current health systems. These challenges require a multidisciplinary approach involving researchers, healthcare professionals, policymakers, and community stakeholders to ensure MPTs fulfil their potential in improving sexual and reproductive health outcomes. This project will introduce an important new product concept combining HIV prevention with treatment of BV.