Ductal carcinoma in situ is the most commonly diagnosed early stage breast cancer. The efficacy of intraductally delivered poly(ethylene glycol)‐doxorubicin (PEG‐DOX) nanocarriers, composed of one or more DOX conjugated to various PEG polymers, was investigated in an orthotopic ductal carcinoma in situ‐like rat model. In vitro cytotoxicity was evaluated against 13762 Mat B III cells using MTT assay. The orthotopic model was developed by inoculating cancer cells into mammary ducts of female Fischer 344 retired breeder rats. The ductal retention and in vivo antitumour efficacy of two of the six nanocarriers (5 kDa PEG‐DOX and 40 kDa PEG‐(DOX)4) were investigated based on in vitro results. Mammary retention of DOX and PEG‐DOX nanocarriers was quantified using in vivo imaging. Histopathologic effects of DOX and PEG‐DOX nanocarriers on mammary ductal structure were also investigated. Cytotoxicities of small linear PEG‐DOX nanocarriers (5 and 10 kDa) were not different from DOX whereas larger PEG‐DOX nanocarriers showed reduced potency. The order of mammary retention was 40 kDa PEG‐(DOX)4 > 5 kDa PEG‐DOX >> DOX, in normal and tumour‐bearing rats. Intraductally administered PEG‐DOX nanocarriers and DOX were effective in reducing tumour incidence and increasing survival rate, with no significant differences found among the three treatment groups. However, nanocarriers administered intravenously at the same doses were not effective, and intraductally administered free DOX caused severe local toxicity. Intraductal administration of PEG‐DOX nanocarriers is effective and less toxic than that of free DOX, as well as IV DOX/PEG‐DOX. Furthermore, PEG‐DOX nanocarriers demonstrate the added benefit of prolonging DOX ductal retention, which would necessitate less frequent dosing.
Background: Meclizine hydrochloride (MCZ) is an antihistamine that is used as an antiemetic to prevent and cure nausea and vomiting. Because of its limited water solubility and first-pass metabolism, it exhibits variable absorption. Objective: To formulate and evaluate MCZ as an intranasal in situ gel with increased residence time and permeability. Methods: We made an inclusion complex of MCZ using various cyclodextrins as a complexing agent to help the drug dissolve better. The complexes were studied, and the ones that were better at dissolving were chosen to be used in the creation of an in situ gel with poloxamer 407 (17–20% w/v) and hyaluronic acid (0.25–0.75% w/v). Prepared formulas were subjected to various evaluation tes
... Show MoreThe objective of this work was to analyze the involvement of AhR in bone metabolism using a rat model of experimental osteoporosis and to analyze the mechanisms behind its activity. Rats were assigned randomly to the subsequent groups; Control, received no treatment; ovariectomized (OVX) rats; Sham; Sham+RES received resveratrol; OVX+RES and OVX+CH received AhR’s antagonist, CH223191 (CH); and finally OVX+CHR group received both AhR antagonist along with resveratrol. Resveratrol and AhR antagonist treatment started 7 days after surgery and continued to 45 days. The serum of osteocalcin (OC) and Ca+2 was measured by ELISA and spectrophotometer, respectively. X-ray was used to estimate bone density of rats. In molecular levels,
... Show MoreSolubility problem of many of effective pharmaceutical molecules are still one of the major obstacle in theformulation of such molecules. Candesartan cilexetil (CC) is angiotensin II receptor antagonist with very low water solubility and this result in low and variable bioavailability. Self- emulsifying drug delivery system (SEDDS) showed promising result in overcoming solubility problem of many drug molecules. CC was prepared as SEDDS by using novel combination of two surfactants (tween 80 and cremophore EL) and tetraglycol as cosurfactant, in addition to the use of triacetin as oil. Different tests were performed in order to confirm the stability of the final product which includes thermodynamic study, determination of self-emulsificat
... Show MoreObjective: The objective of this study was to prepare nanosuspension of a practical water insoluble antiulcer drug which is lafutidine to enhance the solubility, dissolution rate with studying the effect of different formulation variables to obtain the best formula with appropriate physical properties and higher dissolution rate.Methods: Nanosuspension of lafutidine was prepared using solvent anti-solvent precipitation method using Polyvinylpyrrolidone K-90(PVP K-90) as the stabilizer. Ten formulations were prepared to show the effect of different variables in which two formulations showed the effect of stabilizer type, three formulations showed the effect of stabilizer concentration, two formulations showed the effect of combinatio
... Show MoreIn the present study, MCM-41 was synthesis as a carrier for poorly drugs soluble in water, by the sol-gel technique. Textural and chemical characterizations of MCM-41 were carried out by X-ray diffraction (XRD), Fourier transform infrared (FTIR), scanning electron microscope (SEM), and thermal gravimetric analysis (TGA). The experimental results were analyzed mesoporous carriers MCM-41. With maximum drug loading efficiency in MCM-41 determined to be 90.74%. The NYS released was prudently studied in simulated body fluid (SBF) pH 7.4 and the results proved that the release of NYS from MCM-41 was (87.79%) after 18 hr. The data of NYS released was found to be submitted a Weibull model with a correlation coefficient of (0.995). The Historical
... Show MoreDiacerein (DCN) is a semi-synthetic anthraquinone derivative of Rhein that is indicated for the management of osteoarthritis. Diacerein exhibits poor dissolution in the GIT fluids and suffers from low bioavailability upon oral administration in addition to the laxative effect of Rhein metabolites. The aim of the present study was to develop novasomal vesicles with optimized entrapment efficiency and size to serve as a carrier for transdermal delivery of diacerein. Novasomal vesicles were prepared by thin film hydration method thin film hydration. The prepared vesicles were optimized utilizing different surfactant to cholesterol molar ration, sonication type, different sonication times and varying fatty acid level. The prepared vesicles were
... Show MoreBackground: Verrucous carcinoma (VSCC) is considered as a rare well differentiated carcinoma variant of SCC with no metastatic potential. The aim of this study is to evaluate the Immunohistochemical expression MMP-2, VEGF and D2-40 expression in OSCC and VSCC. Materials and methods: Thirty formalin fixed paraffin embedded tissue blocks of OSCC and another twelve VSCC were collected and Four micrometer thick sections were cut from each block and mounted on positively charged slides and stained immunohistochemically with monoclonal antibodies to MMP-2, VEGF and D2-40. Results: there is no statistical difference between SCC and VSCC regarding the immunoexpression of MMP-2 and VEGF. While the lymphatic vessels density were higher in SCC than V
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