Polyion complexes of a cationic antimicrobial peptide as a potential systemically administered antibiotic.

Antimicrobial peptides (AMPs) are regarded as next-generation antibiotics to replace conventional antibiotics due to their rapid and broad-spectrum antimicrobial properties and far less sensitivity to the development of pathogen resistance. However, they are susceptible to proteolysis in vivo by endogenous or bacterial proteases as well as induce the lysis of red blood cells, which prevent their intravenous applications. In this work, polyion complex (PIC) micelles of the cationic AMP MSI-78 and the anionic copolymer methoxy poly(ethylene glycol)-b-poly(α-glutamic acid) (mPEG-b-PGlu) were prepared to develop novel antimicrobial agents for potential application in vivo.

A Drug Carrier for Sustained Zero-Order Release of Peptide Therapeutics.

Peptides have great potential as therapeutic agents, however, their clinic applications are severely hampered by their instability and short circulation half-life. Zero-order release carriers could not only extend the circulation lifetime of peptides, but also maintain the plasma drug level constant, and thus maximize their therapeutic efficacy and minimize their toxic effect. Here using PEGylated salmon calcitonin (PEG-sCT)/tannic acid (TA) film as an example, we demonstrated that hydrogen-bonded layer-by-layer films of a PEGylated peptide and a polyphenol could be a platform for zero-order peptide release.

Metabolic stability of human parathyroid hormone peptide hPTH (1-34) in rat tissue homogenates: kinetics and products of proteolytic degradation.

The present study aim to investigate the metabolic stability and degradation of cleavage sites of human parathyroid hormone peptide, hPTH (1-34), in rat tissue homogenate, and to identify the types of proteases involved in hPTH (1-34) processing degradation. The stability of hPTH (1-34) in rat kidney, lung and liver homogenates was evaluated by LC-ESI-MS, and the structures of the major degradation products were identified by MALDI-TOF MS and LC-ESI-MS/MS. The ability of protease inhibitors to inhibit hPTH (1-34) degradation was used to identify the class of proteases involved in the metabolism of hPTH (1-34).

Novel anti-HIV peptides containing multiple copies of artificially designed heptad repeat motifs.

The peptidic anti-HIV drug T20 (Fuzeon) and its analog C34 share a common heptad repeat (HR) sequence, but they have different functional domains, i.e., pocket- and lipid-binding domains (PBD and LBD, respectively).

Studies of bioactivity, conformation and pharmacokinetic profiles of site-specific PEGylated thymosin alpha 1 derivatives.

Site-specific mono-PEGylations were performed in different conformational regions of Thymosin alpha 1 (T alpha 1) by introducing one cysteine residue into the chosen site and coupling with thiol-specific mPEG-MAL reagent. Results demonstrated that PEGylated sites and regions influenced the conformations and pharmacokinetic profiles of the peptide greatly with following order: alpha-helix, beta-turn, random coil and terminals, but little on the immunoactivity.

Biodegradable PLGA microspheres as a sustained release system for a new luteinizing hormone-releasing hormone (LHRH) antagonist.

A sustained release poly(DL-lactide-co-glycolide) (PLGA) microsphere delivery system to treat prostate cancer for a luteinizing hormone-releasing hormone (LHRH) antagonists, LXT-101 was prepared and evaluated in the paper. LXT-101 microspheres were prepared from PLGA by three methods: (1) double-emulsion solvent extraction/evaporation technique, (2) single-emulsion solvent extraction/evaporation technique, and (3) S/O/O (solid-in-oil-in-oil) method. The microspheres were investigated on drug loading, particle size, surface morphology and in vitro release profiles.