Background: Development of a nanosized polymeric delivery system for erlotinib was the main objective of this research. Materials and Methods: Poly caprolactone-polyethylene glycol-polycaprolactone (PCEC) copolymers with different compositions were synthesized via ring opening polymerization. Formation of triblock copolymers was confirmed by HNMR as well as FT-IR. Erlotinib loaded nanoparticles were prepared by means of synthesized copolymers with solvent displacement method. Results: Physicochemical properties of obtained polymeric nanoparticles were dependent on composition of used copolymers. Size of particles was decreased with decreasing the PCL/PEG molar ratio in used copolymers. Encapsulation efficiency of prepared formulations was declined by decreasing their particle size. Drug release behavior from the prepared nanoparticles exhibited a sustained pattern without a burst release. From the release profiles, it can be found that erlotinib release rate from polymeric nanoparticles is decreased by increase of CL/PEG molar ratio of prepared block copolymers. Based on MTT assay results, cell growth inhibition of erlotinib has a dose and time dependent pattern. After 72 hours of exposure, the 50% inhibitory concentration (IC50) of erlotinib hydrochloride was appeared to be 14.8 μM. Conclusions: From the obtained results, it can be concluded that the prepared PCEC nanoparticles in this study might have the potential to be considered as delivery system for erlotinib.
Epidermal growth factor receptors (EGFRs) have potential to be considered as therapeutic target for cancer treatment especially in cancer patients with overexpression of EGFR. Cetuximab as a first monoclonal antibody and Imatinib as the first small molecule tyrosine kinase inhibitor (SMTKI) were approved by FDA in 1998 and 2001. About 28 SMTKIs have been approved until 2015 and a large number of compound with kinase inhibitory activity are at the different phases of clinical trials. Although Kinase inhibitors target specific intracellular pathways, their tissue or cellular distribution are not specific. So treatment with these drugs causes serious dose dependent side effects. Targeted delivery of kinase inhibitors via dendrimers, polymeric nanoparticles, magnetic nanoparticles and lipid based delivery systems such as liposomes, solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) can lead to reduction of side effects and improving therapeutic efficacy of the drugs in the target organs. Furthermore formulation of these drugs is challenged by their physicochemical properties such as solubility and dissolution rate. The main approaches in order to increase dissolution rate, are particle size reduction, self-emulsification, cyclodextrin complexation, crystal modification and amorphous solid dispersion. Synergistic therapeutic effect, decreased side effects and drug resistant, reduced cost and increased patient compliance are the advantages associated with using combination therapy especially in the treatment of cancer. Combination of TKIs with chemotherapeutic agents or biopharmaceuticals such as monoclonal antibodies and oligonucleotides and also combination of two TKIs within one formulation is possible by new targeting delivery systems. This article reviews the recent advances in the design and development of delivery systems for TKIs.
Background: Chlorpheniramine maleate (CM) is widely used as an antihistaminic drug but it is very bitter and as yet no mouth dissolving/ disintegrating taste-masked preparation that might be useful for pediatric and geriatric patients is available in the market. Objectives: The purpose of this research was to mask the bitter taste of CM by formulating microspheres of the taste-masked drug. Materials and Methods: This work was done to develop alginate/chitosan particles prepared by ionic gelation (Ca 2+ and Al 3+ ) for the CM release. The effect of different chitosan and Ca 2+ concentrations on taste masking and the characteristics of the microspheres were investigated. Ca 2+ and Al 3+ alginates microspheres of CM were prepared using cross-linked insoluble complexes that precipitate, incorporating the drug. Formulations were characterized for particle size and shape, entrapment efficiency, fourier transform spectroscopy (FTIR), x-ray diffraction (XRD), and differential scanning calorimetry (DSC), bitter taste threshold and in vitro drug release in simulated gastrointestinal fluids. Results: FTIR, XRD and DSC demonstrated unstable characters of CM in the drug-loaded microspheres and revealed an amorphous form. Also, the peak of alginate microparticles (Ca 2+ and Al 3+ ions) in all formulations remained the same, with low intensity of spectrum. The results of DSC, X-ray diffraction and FTIR showed the presence of several CM chemical interactions with alginate and ions (Ca 2+ and Al 3+ ). The microsphere formulations showed desirable drug entrapment efficiencies (62.2-94.2%). Calcium/aluminum alginate retarded the release of CM at low pH = 1.2 and released the drug from microspheres slowly at pH = 6.8, simulating intestine pH. The drug release duration and the release kinetics were dependent on the nature of the polymers, the cation concentrations, and valences (Ca 2+ and Al 3+ ). The drug release rate was decreased by an increase in chitosan and cation concentrations. Conclusions:The results of the present study indicated that oral preparation of CM with an acceptable taste is feasible.
Based on the obtained results the two fexofenadine formulations are considered to be equivalent.
Phencyclidine (1-(1-phenylcyclohexyl)piperidine, CAS 956-90-1, PCP, 1) and ketamine (2-O-chlorophenyl-2-methylaminocyclohexan, CAS 1867-66-9, II) revealed some analgesic effects. Some of their derivatives have been synthesized for biological properties studies. Utilizing 1-tetralone as a starting material, 1-[1-(3-methylphenyl)(tetralyl)]piperidine, (PCP-CH3-tetralyl, III) was synthesized and its analgesic effects were studied on rats via tail immersion (as a model of acute thermal pain) and formalin (as a model of acute chemical and chronic pain) tests and compared with those of ketamine and PCP. The results indicated a marked anti-nociception 2-25 min after ketamine injection, but this analgesic effect lasted for 40 min following PCP-CH3-tetralyl application in the tail immersion test. However, the data obtained from the formalin test showed that chronic pain could be significantly attenuated by ketamine, PCP and PCP-CH3-tetralyl.
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