| Title | Formulation of biologics as dry powders for inhalation |
|---|---|
| Supervisors | Luis Bimbo Gavin Halbert |
| Research Area | Drug Delivery, Biologics, Dry Powders for Inhalation, Pulmonary Delivery |
| Description | Biologics are therapeutic proteins or peptides that are produced by means of biological processes within living organisms and cells and constitute now a significant proportion of the therapeutic modalities used in the treatment of various diseases [1]. However, peptide therapeutics possess short in vivo half-life, ranging from a few minutes to a few hours. In fact, the successful use of a peptide therapeutic formulation depends on its long-term chemical and physical stability and storage [2]. In order to circumvent some of these challenges, the inhalation route offers great potential for rapid (within seconds or minutes) systemic delivery of therapeutic molecules with fewer degradation barriers. Because of the huge surface area of the lungs, the highly dispersed nature of aerosols, good epithelial permeability and small aqueous volume at the absorptive surface, inhalable formulations offer significant advantages when compared to their intravenous counterparts [3]. In this project, several therapeutic peptides are to be formulated as dry powders for inhalation (DPI) using a flow reactor method [4] or aerosol jet printing which prevents denaturation and loss of activity of formulated peptides and proteins, while enabling multiple active pharmaceutical ingredients (APIs) cargoes to be loaded simultaneously in the same powder particle. The formulations will be characterised for their flowability, particle size, morphology, aerosolisation properties and drug loading. Long- and short-term shelf-life stability studies are to be conducted, as well as in vitro drug permeation and cytotoxicity. Finally, in vivo assessment of the peptide’s activity is to be conducted and compared with the intravenous route. |
| Techniques Used | 1) Formulating biologics as dry powders for inhalation using the flow reactor method and aerosol jet printing; 2) Characterising the dry powders for inhalation using 1D and 2D NMR, SEM, Elemental Analysis, Aerosol Inhalation Device, and HPLC. 3) In vitro characterisation of the formulation using Circular Dichroism, Cell Culture of Immortalised Lung Cells, and ELISA. 4) In vivo activity assessment using disease-specific mice models which mimic the several pathophysiological conditions currently being treated with intravenous delivery of peptides. |
| References | [1] Nat. Rev. Drug Discov. 18 (2018) 19–40. doi:10.1038/nrd.2018.183. [2] Nat. Rev. Drug Discov. 4 (2005) 298–306. doi:10.1038/nrd1695. [3] Int. J. Pharm. 544 (2018). doi:10.1016/j.ijpharm.2018.04.019. [4] Pharm. Res. 34 (2017) 25–35. doi: 10.1007/s11095-016-2035-9. |
| Conditions | Applicants should possess or be about to obtain a 1st class or 2:1 Honours degree or equivalent in a relevant discipline in addition to receipt of satisfactory references and an IELTS score of 6.5 where appropriate. Relevant subjects include Pharmacy, Pharmaceutical Sciences, Engineering, Biochemistry, Biomedical Sciences, Chemistry or a closely related discipline. |
| Bench Fee | Running costs of £12500 p.a. will be associated with this project in addition to University tuition fees. |
| Suitable For | motivated candidates who have demonstrated high academic attainment to date. |
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