The increasing spread of antibiotic resistance among bacteria poses a major threat to the public health. There is an urge for the development of innovative formulations of existing and new antibiotics. One area of interest is in wound care, where two interesting antimicrobials are the conventional antibiotic amoxicillin and the antimicrobial peptide AP114. The objective of this work was to systemically evaluate topical gel formulations of these APIs by following a Quality by Design approach. A short excipient compatibility study was performed and the thickening agents poloxamer 407 and HPMC were chosen to be included in the following Design of Experiment (DoE) study of formulation composition and storage climate. The DoE set up was generated by the software MODDE Pro® and a short stability study of four weeks was performed, including analysis of the apparent pH, rheology stability, appearance, BCA assay, UV-Vis and FTIR spectroscopy and Franz cell diffusion. The results showed that AP114 formulations stored at 2-8˚C with poloxamer 407 should be with buffer pH 5-6 and 5-15 wt% organic phase to maximize stability, while HPMC based AP114 gels should be with buffer pH 6-8 and 10-40 wt% organic phase. Poloxamer 407 was not preferrable for amoxicillin formulations. The optimal HPMC based amoxicillin formulations included the storage temperature 25˚C, a buffer pH 7-8 and 40-60 wt% organic phase. HPMC based amoxicillin gels stored at 2-8˚C should be composed with buffer pH 6-8 and 10-40 wt% organic phase.

Bakterier som är resistenta mot antibiotika har de senaste åren blivit ett stort hot mot mänskligheten. Att utveckla nya antibiotikaläkemedel är väldigt tidskrävande samt kommer med en dyr prislapp. Det är några av anledningarna att forskare har inriktat sig på antimikrobiella peptider (AMPs) som ett alternativ till traditionella antibiotika. Dessa peptider finns i alla levande organismer och uppvisar en snabb och ospecifik mekanism. Vidare så är de mindre benägna att utveckla resistens hos bakterierna. Däremot så har dessa AMPar visat sig ha låg stabilitet och en del toxiska biverkningar. Olika typer av nanobärare kan användas för att överkomma dessa kommakortanden. Syftet med denna studie var att utveckla en optimerad nanobärare för AMPen AP114. Peptiden har blivit inkluderad i nanostrukturerade lipidbärare (NLC) samt liposomer. Dessa har producerats med smält emulsifieringsmetod och lösningsinjektion metoden. De fysikalkemiska karaktäristik hos olika blanka samt AP115 laddade nanoformuleringar har analyserats samt jämförts. Resultaten indikerade att liposomformuleringarna hade den lägsta partikelstorleken och storleksfördelning men en kontrollerad in vitro frisättning av peptiden över 48 timmar. Generellt, så indikerar de preliminära resultaten en potential nanoformulering för peptiden AP114. / In the past few years, bacterial resistance to antibiotics has posed a major threat to humankind. Development of substitutes for traditional antibiotics is a highly time consuming and expensive venture. For this reason, researchers are focusing on using antimicrobial peptides (AMP) as an alternate. These peptides are found in all living organisms and exhibit a fast and non-targeted mechanism of action. Besides, they are less susceptible to microbial resistance. However, these therapeutic peptides are not stable and have toxic side effects. To overcome these limitations, drug delivery systems have been explored. In this study, the aim was to develop an optimized drug delivery system for AP114. The peptide has been encapsulated in nanostructured lipid carriers (NLC) and liposomes, produced by melt emulsification method and solvent injection method, respectively. The physicochemical characterization of different blank and AP114 loaded nanoformulations were analyzed and compared. The results indicated the liposome samples to have the lowest particle size distribution and polydispersity, with a controlled in vitro release of the peptide over 48 hours. Overall, these preliminary findings suggest a promising potential for the formulation of a nanocarrier for AP114 peptide.