Lipoglycopeptide Antibacterial Agents in Gram-Positive Infections: A Comparative Review.

Oritavancin, telavancin, and dalbavancin are recently marketed lipoglycopeptides that exhibit remarkable differences to conventional molecules. While dalbavancin inhibits the late stages of peptidoglycan synthesis by mainly impairing transglycosylase activity, oritavancin and telavancin anchor in the bacterial membrane by the lipophilic side chain linked to their disaccharidic moiety, disrupting membrane integrity and causing bacteriolysis. Oritavancin keeps activity against vancomycin-resistant enterocococci, being a stronger inhibitor of transpeptidase than of transglycosylase activity. These molecules have potent activity against Gram-positive organisms, most notably staphylococci (including methicillin-resistant Staphylococcus aureus and to some extent vancomycin-intermediate S. aureus), streptococci (including multidrug-resistant pneumococci), and Clostridia. All agents are indicated for the treatment of acute bacterial skin and skin structure infections, and telavancin, for hospital-acquired and ventilator-associated bacterial pneumonia. While telavancin is administered daily at 10 mg/kg, the remarkably long half-lives of oritavancin and dalbavancin allow for infrequent dosing (single dose of 1200 mg for oritavancin and 1000 mg at day 1 followed by 500 mg at day 8 for dalbavancin), which could be exploited in the future for outpatient therapy. Among possible safety issues evidenced during clinical development were an increased risk of developing osteomyelitis with oritavancin; taste disturbance, nephrotoxicity, and risk of corrected QT interval prolongation (especially in the presence of at-risk co-medications) with telavancin; and elevation of hepatic enzymes with dalbavancin. Interference with coagulation tests has been reported with oritavancin and telavancin. These drugs proved non-inferior to conventional treatments in clinical trials but their advantages may be better evidenced upon future evaluation in more severe infections

Templated Ultrathin Polyelectrolyte Microreservoir for Delivery of Bovine Serum Albumin: Fabrication and Performance Evaluation

The aim of the study was to develop ultrathin polyelectrolyte microreservoir (UPM) using two combinations of synthetic/synthetic (S/s; poly(allylamine hydrochloride) (PAH)/sodium poly(styrenesulfonate)) and synthetic/natural (S/n; PAH/sodium alginate) polyelectrolytes over spherical porous CaCO3 core particles (CP) followed by core removal and to evaluate its biocompatibility and integrity of loaded model protein bovine serum albumin (BSA). A novel process for synthesis of CP was developed to obtain maximum yield of monodisperse vaterite (spherical) polymorph. The prepared UPM was characterized for surface morphology, layer-by-layer growth, pay load efficiency, integrity of BSA, as well as viability and cell adhesion using murine J 774 macrophages (Φ). In vitro release profile revealed that both S/s and S/n UPM were able to provide sufficient diffusion barrier to release protein at physiological pH. It has been observed that S/n UPM are fully biocompatible due to obvious reason of using natural polymer. In a separate experiment, the S/s UPM surface was modified with pluronic F-68 to tune biocompatibility which provides evidences for safety and tolerability of the S/s UPM as well. In nutshell, the proposed system could successfully be used for the delivery of proteins, and moreover, the system can be tailored to impart desired properties at any stage of layering especially in terms of drug release and to retain the integrity of proteins