Novel antifungal peptides are described with some peptides exhibiting selective activity againstC. neoformans. Cytotoxicity and mechanistic studies reveal their applicability as effective antimicrobials with less susceptibility to drug resistance.
Two series of short cationic antimicrobial peptides (CAMPs) in which modification of the imidazole ring of histidine by bulkier alkyl substituents was done using regiospecific and radical‐mediated alkylation. The synthesized CAMPs were evaluated for their antibacterial efficacy using different bacterial strains. In particular, CAMP 11 i was found to be most active against L. monocytogenes and other CAMPs such as 10 e and 11 g exhibited moderate activity against S. aureus.The most active compounds were tested against Hek‐293 and HeLa cells with active CAMPs 11 i and 11 g with calculation of selectivity index against the L. monocytogenesand S. aureus, respectively as compared to mammalian cells. The SEM studies were also performed which confirmed the disruption of cell wall of treated bacteria using CAMP 11 i at its MIC concentration. The selectivity of active peptides towards bacterial cells in comparison to mammalian cells was checked using tryptophan quenching studies on small unilamellar vesicles. The results were found to be perfectly in corroboration with the differences between bacterial and mammalian cell membrane composition, thereby, indicating that these peptides kill the bacterial cells via conjugation with the cell membrane. Synergy studies of CAMPs in combination with known clinical antibacterial drugs against L. monocytogenes further displayed enhanced antibacterial efficacy.
Thyrotropin-Releasing Hormone (TRH), a tripeptide amide with molecular formula L-pGlu-L-His-L- Pro-NH2, is used in the treatment of brain/spinal injury and certain central nervous system (CNS) disorders, including schizophrenia, Alzheimer's disease, epilepsy, depression, shock and ischemia due to its profound effects on the CNS. However, TRH's therapeutic activity is severely hampered because of instability and hydrophilicity owing to its peptidic nature which results into ineffective penetration into the blood brain barrier. In the present study, we report the synthesis and stability studies of novel chitosan engineered TRH encapsulated poly(lactide-co-glycolide) (PLGA) based nanoformulation. The aim of such an encapsulation is to allow effective delivery of TRH in biological systems as the peptidase degrade naked TRH. The synthesis of TRH was carried out manually in solution phase followed by its encapsulation using PLGA to form polymeric nanoparticles (NPs) via nanoprecipitation technique. Different parameters such as type of organic phase, concentration of stabilizer, ratio of organic phase and aqueous phase, rate of addition of organic phase were optimized, tested and evaluated for particle size, encapsulation efficiency, and stability of NPs. The TRH-PLGA NPs were then surface modified with chitosan to achieve positive surface charge rendering them potential membrane penetrating agents. PLGA, PLGA-TRH, Chitosan-PLGA and Chitosan-PLGA-TRH NPs were characterized and analyzed using Dynamic Light Scattering (DLS), Transmissiom Electron Microscopy (TEM) and Infra-red spectroscopic techniques.
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