Formulation Development and Evaluation of Protein based Nano Particulate system for treatment of Pulmonary Infections

Abstract

The aim of this research work was to focused on the development of a novel newlinenanotechnology enabled DDS suitable for pulmonary protein and peptide newlinedelivery, using novel excipients. In the same context, the synthesis and newlinecharacterization of starch derivatives was performed, including an newlineoptimization of product purification performed by precipitation of the newlinematerial, as well as introducing an alternative coupling agent, DMTMM. newlineIn summary, these findings underline the close interplay between knowledge newlineof the material used for drug delivery preparation, and in vitro testing newlineapproaches, in addition to the development of a suitable DDS for APIs from newlinea technological viewpoint. Additionally, in the case of proteins and peptides newlineas API, a sound knowledge of their characteristics is also necessary. newlineAlthough a few questions could be answered in the current work, several newlineopen questions still remain and could form the basis of future work. In the newlinecourse of material synthesis an alternative coupling reagent was found in newlineDMTMM, and an improvement in the purification method could be shown; newlinehowever, scalability from milligram to gram, and further to kilogram, is of newlineinterest from an industrial point of view. newlineFurthermore, although a possible explanation for the apparent newlineimmunogenicity of the system was found namely, contamination with newlineendotoxins, the application of different elimination techniques (e.g. with newlineEndoTrap®) followed by further evaluation with the endoLISA are of newlineimportance to substantiate this hypothesis. newlineCytotoxicity and immunogenicity data should also be repeated in newlineconjunction with such investigations. NP preparation and loading was newlinesuccessful with model proteins. The loading with an actual disease-relevantii newlinecargo with subsequent efficacy testing is done and , the release kinetics from newlineNPs had been investigated. The microparticles, especially Starch + mannitol newlineshowed a high degree of deposition in the deep lung with a considerable newlineuptake of starch NPs, when deposited as dry powder formulation.