Enhanced antisense effect of modified PNAs delivered through functional PMMA microspheres.

Peptide nucleic acids (PNA) are very promising antisense agents, but their in vivo application is often hampered by their low bioavailability, mainly due to their limited uptake through cellular and nuclear membranes. However, PNA chemical synthesis easily allows modification with functional structures able to improve the intrinsically low permeability and great interest is arising in finding specific and efficient delivery protocols. Polymeric core-shell microspheres with anionic functional groups on the surface were tested for their ability to reversibly bind lysine modified PNA sequences, whose antisense activity against COX-2 mRNA was already demonstrated in murine macrophages.

Erythrocyte-based drug delivery.

The use of a physiological carrier to deliver therapeutics throughout the body to both improve their efficacy while minimising inevitable adverse side effects, is an extremely fascinating perspective. The behaviour of erythrocytes as a delivery system for several classes of molecules (i.e.

Comparison of novel delivery systems for antisense peptide nucleic acids.

Peptide nucleic acids (PNAs) provide a powerful tool to study the mechanism of transcription and translation, an innovative strategy to regulate target gene expression. They have been successfully used in antisense technology, for their ability to specifically bind to messenger RNA (mRNA) targets and to inhibit translation of the target genes. However, unlike most of the DNA and RNA oligonucleotides, PNAs are poorly penetrated through the cell membrane, partially due to their uncharged property.

Novel biocompatible anionic polymeric microspheres for the delivery of the HIV-1 Tat protein for vaccine application.

Two novel classes of biocompatible core-shell anionic microspheres, composed of an inner hard insoluble core, either made of poly(styrene) (PS) or poly(methyl methacrylate) (PMMA), and a soft outer tentacular shell made of long soluble negatively charged arms derived from the steric stabilizer, hemisuccinated poly(vinyl alcohol) or Eudragit L100/55, respectively, were prepared by dispersion polymerization and characterized. Five types of these novel microspheres, two made of poly(styrene) and hemisuccinated poly(vinyl alcohol) (A4 and A7), and three made of poly(methyl methacrylate) and Eudragit L100/55 (1D, 1E, H1D), differing for chemical composition, size, and surface charge density were analyzed for the delivery of the HIV-1 Tat protein for vaccine applications. All microspheres reversibly adsorbed the native biologically active HIV-1 Tat protein preventing Tat from oxidation and maintaining its biological activity, therefore increasing the shelf-life of the Tat protein vaccine.

Core-shell nanospheres for oligonucleotide delivery. V: adsorption/release behavior of 'stealth' nanospheres.

The adsorption/release behavior of oligodeoxynucleotides (ODNs) on new PEGylated core-shell polymethylmethacrylate nanospheres is described. The outer shell consists of alkyl chains containing quaternary ammonium groups and of poly(ethylene glycol) chains, both covalently bound to the inner core. Ion pair formation between negatively charged ODN phosphate groups and positively charged groups on the nanosphere surface is the main interaction mechanism.

Dinuclear copper(II) complex as nitric oxide scavenger in a stimulated murine macrophage model.

Nitric oxide is a gaseous, short-living free radical which behaves as an important signaling molecule with pleiotropic capacities including vasodilatation, neurotransmission, and microbial and tumor cell killing, as well as in tissue damage and organ-specific autoimmune disorders. Here, a synthesized, dinuclear copper complex system in vitro obtained by the simple aza-phenolic ligand 2,6-bis[[bis-(2-aminoethyl)amino]methyl]phenol (L) and Cu(II) ion has been used. The stability constants of ligand L with Cu(II) ion were determined through potentiometric measurements in aqueous solution (37.

Pharmacokinetic and antiretroviral activity in mice of oral [P(1),P(2)-bis[2-(adenin-9-yl)ethoxymethyl]phosphonate], a prodrug of 9-(2-phosphonylmethoxyethyl)adenine.

9-(2-Phosphonylmethoxyethyl)adenine (PMEA) is an antiviral drug with activity against herpes viruses, Epstein-Barr virus and retroviruses, including the human immunodeficiency virus. Unfortunately, oral PMEA administration, as required for long-term therapy, is hindered by its low bioavailability. In the present study, the synthesis, oral bioavailability and antiretroviral activity of a new prodrug of PMEA, consisting of two molecules of PMEA bound together by a P-O-P bond (Bis-PMEA), are reported.

Inhibition of macrophage iNOS by selective targeting of antisense PNA.

Peptide nucleic acids (PNAs) are synthetic polynucleobases that bind to DNA and RNA with high affinity and specificity and with poor membrane permeability. Although PNAs have an enormous potential as antisense agents, the success of antisense PNA applications will require efficient cellular uptake. In this study, a unique antisense 14-mer anti-inducible nitric oxide synthase (iNOS) was encapsulated into erythrocytes (RBC) by hypotonic dialysis.