Subcutaneous administration of biological drugs has become highly attractive as it offers the possibility for patient self-administration. Coacervates as a subcutaneous drug delivery system provide a way to decrease injection volumes thereby reducing the risk of injection site pain. The aim with this thesis was to investigate possible coacervation between polyelectrolytes and peptide drugs under various physicochemical conditions. In this project, hyaluronic acid (HA) and carboxymethylcellulose (CMC) and their ability to coacervate with polymyxin B (PB) and vancomycin (VA) was studied. Furthermore, the release of these peptide drugs from the formulations into a release medium mimicking the subcutaneous environment was studied using UV spectroscopy. Studies showed successful coacervation between VA-CMC, PB-CMC and PB-HA. VA-CMC and PB-CMC coacervates were formed at higher peptide-polyelectrolyte charge ratios and lower ionic strengths at pH 7. The increase in charge ratio seemed to eliminate steric effects caused by the polyelectrolyte chains that most likely hindered coacervation. Furthermore, PB-CMC and PB-HA formed gel-like coacervates in the pH range of 11.73-11.84 at 1:1 charge ratio and ionic strengths 0-70mM. At such high pH values, the obtained formulations were most likely a result of PB-PB aggregation or charge regulation. From drug release studies one could conclude that VA-CMC exhibits direct release followed by a slower prolonged release profile. PB-CMC coacervates, liquid and gel, showed a sustained release profile while the PB-HA gel formulation resulted in direct release. Unfortunately, due to limitations with the experimental release rate set-up, the conclusions drawn can not be considered 100% reliable.
| Identifer | oai:union.ndltd.org:UPSALLA1/oai:DiVA.org:uu-478437 |
| Date | January 2022 |
| Creators | Elkhalifa, Dania |
| Publisher | Uppsala universitet, Institutionen för läkemedelskemi |
| Source Sets | DiVA Archive at Upsalla University |
| Language | English |
| Detected Language | English |
| Type | Student thesis, info:eu-repo/semantics/bachelorThesis, text |
| Format | application/pdf |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | UPTEC K, 1650-8297 ; 22014 |
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