PREPARATION OF TMC NANOPARTICLES FOR OCULAR DELIVERY

Purpose:. The use of povidone iodine to treat conjunctivitis is well known, but it requires the administration of povidone iodine solution several times daily, generally associated to other antibacterial agents. The aim of this work was to prepare povidone iodine loaded N-trimethyl chitosan nanoparticles (PI-TMC NP) for ocular delivery, in order both to obtain a formulation at controlled and prolonged release and a transcorneal drug transport. Methods: TMC has been synthesized through methylation reaction with methyl iodide in basic medium to obtain a polymer with a DQ around 27 %. PI-TMC NP have been prepared through ionotropic gelation method using tripolyphoshate (TPP). We prepared two different formulations of PI- TMC NP (5% w/w and 5% w/v) and we characterize them in the aim to choose the best one for therapeutic use. The obtained polymer has been characterized by means of spectroscopic methods (FTIR, 1H-NMR and XRD). The freeze dried polymer and the PI- TMC NP have been analysed by CP-MAS 13C. Water dispersions of TMC have been submitted to physical- chemical analyses, such as determination of pH, rheological, evaporation-freezing assays and stability studies. Results: The particle-size and zeta potential of the PI- TMC NP were measured with a Malvern Zetasizer Nano. The particle-size distribution of the nanoparticles is reported as polydispersity index (PDI). Loading capacity and efficacy assays have been performed together with preliminary release studies. In vitro preliminary release tests showed that povidone iodine has been released from the polymer matrix in a prolonged and controlled manner.Conclusions: On the bases of above TMC nanoparticles could be considered a promising carrier for prolonged and controlled ophthalmic drug delivery system

Synthesis of new arylidencycloalkylpyrazoles of potential biological interest

Indazoles and pyrazoles are known to be pharmaceutically relevant molecules. In particular their application as both analgesic and antitumoral drugs has been reported. In order to investigate the properties of compounds belonging to these families, we have synthesised new cycloalkylpyrazoles bearing an arylidene group on the cycloalkyl ring, with the aim of modifying the biological profile of these molecules

Synthesis And Characterization Of A Chitosan Derivative For The Preparation Of Nanoparticles

N-trimethyl chitosan (TMC) is a partially N-chitosan quaternary derivative readily soluble at physiological pH, with mucoadhesive properties, high biocompatibility and biodegradability. The aim of this work is to obtain TMC with different degrees of quaternization, slightly modifying the synthetic procedures reported in literature [1]. Appropriately quaternized TMC was used to prepare nanoparticles drug delivery systems, suitable to be administered orally, ocularly or parenterally. TMC derivatives were characterized by means of spectroscopic methods (I.R and 1H- NMR) and XRD. Water dispersions of TMC were submitted to physical-chemical analyses, such as pH, rheological and evaporation- freezing assays, and stability studies. TMC nanoparticles were prepared by ionotropic gelation technique with tripolyphosphate (TPP). Preliminary morphological examination of the nanoparticles was performed by scanning electron microscopy (SEM). The size and zeta potential of the TMC nanoparticles were measured with a Malvern Zetasizer Nano. 1H-NMR studies (performed on a Varian 500MHz spectrophotometer) confirmed that TMC derivatives with different degrees of quaternization were obtained and these derivatives were suitable for different routes of administration. As a matter of fact apparent viscosity data of dispersions remain relatively unchanged over time and the good stability of the water solutions was confirmed by 1H- NMR spectra. Finally TMC nanoparticles exhibit good PDI values and are stable over time

Shape based computer aided similarity screening: a valid tool in the discovery of new scaffolds for the inhibition of HIV-1 reverse transcriptase associated ribonuclease H function

Background. The human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) is one of the most attractive targets in the design of new antivirals. It is a key enzyme for viral replication which has two associated catalytic functions: a DNA polymerase activity, that recognizes both RNA and DNA as template, and a ribonuclease H (RNase H) activity that selectively degrades the RNA of the hybrid RNA:DNA replicative intermediate. Recently, a few hydrazone derivatives has been reported to selectively inhibit the HIV-1 RNase H function. Methods. The highly optimized screening platform Rapid Overlay of Chemical Structures (ROCS) was used to perform in silico similarity screening. HIV-1 RT activities were measured in biochemical assays and HIV-1 replication was tested in cell culture assays. Results. We focused on the design of new scaffolds for the inhibition of the HIV-1 RT-associated RNase H function by performing a computer sided shape based similarity screening study whose driving force is the assumption that molecules with similar shape to known active ones should exhibit comparable biological properties. In particular, using the highly optimized screening platform ROCS for shape-based virtual screening of the large database obtained from the National Cancer Institute we have identified a set of molecules characterized by different scaffolds which have been tested on the HIV-1 RT functions. Compounds with different scaffolds have shown to inhibit one or both RT-associated activities. Conclusions. New scaffolds for the inhibition of the HIV-1 RT-associated RNase H function have been identified and will be further developed