Poster 102 pharmmatoxico

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Poster 102 pharmmatoxico

  1. 1. CHITOSAN NANOPARTICLES AS CARRIER FOR “ZIDOVUDINE” AN ANTI HIV DRUG Dahmane 1 , Taourirte 1 , Rhazi 2 , Belfkira 1 , Fertah 1 . 1-Laboratoire de chimie Bio organique et Macromoléculaire, Département des Sciences Chimiques, Faculté des Sciences et Techniques Guéliz, Marrakech, Morocco 2-Laboratoire des Macromolécules Naturelles, Ecole Normale supérieure, Marrakech, Morocco. 2011 Pharma-toxicologie Poster 102
  2. 2. 2011 Pharma-toxicologie Poster 102 Introduction: Chitosan is currently receiving a great deal of attention for medical and pharmaceutical applications due to its biocompatibility, high charge density, non-toxicity, low immunogenicity and mucoadhesion, chitosan has been extensively investigated for formulating carrier and delivery systems. This polymer is an opportunity for formulation scientists to overcome the many challenges associated with antiretroviral drug therapy such as poor solubility, low bioavailability and the short half-life. Zidovudine was the first clinically approved nucleoside reverse transcriptase inhibitor widely used for the treatment of acquired immunodeficiency syndrome (AIDS) caused by the human immunodeficiency virus (HIV). It has been used in many anti-HIV combination therapies including the suppression of HIV transmission from mother to fetus. The clinical limitations of zidovudine are its short plasma half-life (approximately 1 h), and its dose-dependent toxicities, especially granulocytopenia and anemia, often found in zidovudine-treated patients.
  3. 3. 2011 Pharma-toxicologie Poster 102 Introduction: The purpose of the present work was to create biodegradable nanoparticles based on natural polysaccharide c.a. chitosan and evaluate for the first time to our knowledge their potential as carrier for an anti-HIV zidovudine . These nanoparticles were prepared by gelation of chitosan by ionic cross-linking with tripolyphosphate and characterized in term of their morphology, association efficiency and in vitro release behaviors .
  4. 4. 2011 Pharma-toxicologie Poster 102 Methods: The zidovudine loaded chitosan nanoparticles are prepared by gelation of chitosan with tripolyphosphate by ionic cross-linking and quantified by an HPLC method. The physicochemical properties of nanoparticles are investigated by FTIR and scanning electron microscopy. Figure 1 : Chemical structures of chitosan, T ripolyphosphate and Zidovudine (AZT) . Chitosan T ripolyphosphate Zidovudine
  5. 5. 2011 Pharma-toxicologie Poster 102 Results and discussion: FTIR analysis: The FT-IR spectrum of chitosan-tripolyphosphate (CS-TPP) nanoparticles is different from that of chitosan (CS) matrix (Figure 2). In CS-TPP nanoparticles the 1597.5 cm–1 peak of N-H bending vibration shifts to 1533.3 cm–1. The peak at 1660.3 cm–1 disappears, and a new sharp peak at 1630.1 cm–1 appears. This difference it could be attributed to linkage between phosphoric and ammonium ions. Figure 2 : FT-IR spectra of Chitosan matrix and Blank CS-TPP-nanoparticles
  6. 6. 2011 Pharma-toxicologie Poster 102 Results and discussion: FTIR analysis: In the Blank CS-TPP-nanoparticles spectrum, the strong peak centered at 3400.5 cm-1 shifts to 3431.3 cm-1 in the combined AZT loaded nanoparticles, which are due to the interaction range corresponds to combined peaks of O-H stretching and intermolecular hydrogen bonding of chitosan with participation of O-H of AZT (Figure 3). Figure 3 : FT-IR spectra of AZT, Blank CS-TPP-nanoparticles and combined AZT loaded nanoparticles
  7. 7. 2011 Pharma-toxicologie Poster 102 Results and discussion: Morphological characterization: The surface morphology of nanoparticles is observed by scanning electron microscopy (SEM). The nanoparticles (Figure 4) showed their surface morphology; that they are about 250 nm in diameter and spherical. Figure 4 : SEM images of combined AZT loaded chitosan nanoparticles.
  8. 8. 2011 Pharma-toxicologie Poster 102 The influences of chitosan MW on AZT release behaviour (  , 13  , 63 kDa) The influences of AZT initial concentrations on it release behavior (  , 1  , 2  4 mg/ml) The influences of the TPP concentration on AZT release behaviour (  , 2.5  , 5  10 mg/ml) Conclusion : Nanoparticles loaded with AZT were successfully prepared by gelation of chitosan with TPP by ionic cross-linking.The release rate of AZT depends on chitosan molecular weight. As different loaded mode, the influences of the initial AZT amount and TPP concentration on AZT release are apparent.

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