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Evaluation of intraductal delivery of poly(ethylene glycol)‐doxorubicin conjugate nanocarriers for the treatment of ductal carcinoma in situ (DCIS)‐like lesions in rats
Abstract<p>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)<sub>4</sub>) 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)<sub>4</sub> > 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.</p>
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Publication Date
Sun Sep 15 2024
Journal Name
Iraqi Journal Of Pharmaceutical Sciences( P-issn 1683 - 3597 E-issn 2521 - 3512)
Preparation and In vitro/Ex vivo Evaluation of Nanoemulsion-Based in Situ Gel for Intranasal Delivery of Lasmiditan

Lasmiditan (LAS) was formulated as a nanoemulsion based in situ gel (NEIG)with the aim of improving its oral bioavailability via application intranasally. The solubility of LAS in oils, emulsifiers, and co-emulsifiers was determined to identify nanoemulsion (NE)components. Phase diagrams were constructed to identify the area of nanoemulsification. LAS NE was formulated using the spontaneous nanoemulsification method. Four NEs (F19, F24, F31, and F34) containing 7-15 % oleic acid (OA) as an oily phase, 40-55% labrasol (LR), and transcutol (TC) as emulsifier mixture at (1:1), (2:1), (3:1), and (1:2) ratio with 30-53 % (w/w) aqueous phase, having suitable optical transparency of 95–98%, globule size of 104-140 nm and polydisper

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Publication Date
Fri Dec 01 2023
Journal Name
Physical Chemistry Research
Thermophysical Study of Ethylene Glycol + H<inf>2</inf>O and Ethylene Glycol + (DMF/H<inf>2</inf>O) at 298.15 K

n this research, some thermophysical properties of ethylene glycol with water (H2O) and two solvent mixtures dimethylformamide/ water (DMF + H2O) were studied. The densities (ρ) and viscosities (η) of ethylene glycol in water and a mixed solvent dimethylformamide (DMF + H2O) were determined at 298.15 K, t and a range of concentrations from 0.1 to1.0 molar. The ρ and η values were subsequently used to calculate the thermodynamics of mixing including the apparent molar volume (ϕv), partial molar volume (ϕvo) at infinite dilution. The solute-solute interaction is presented by Sv results from the equation ∅_v=ϕ_v^o+S_v √m. The values of viscosity (B) coefficients and Falkenhagen coefficient(A) of the Jone-Dole equation and Gibbs free

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Publication Date
Tue Apr 26 2022
Journal Name
Journal Of Contemporary Medical Sciences
Doxorubicin Immobilization on chitosan-modified silver Nanoparticles as a drug delivery method for effective anticancer treatment

Objective: The goal of this research is to load Doxorubicin (DOX) on silver nanoparticles coupled with folic acid and test their anticancer properties against breast cancer. Methods: Chitosan-Capped silver nanoparticles (CS-AgNPs) were manufactured and loaded with folic acid as well as an anticancer drug, Doxorubicin, to form CS-AgNPs-DOX-FA conjugate. AFM, FTIR, and SEM techniques were used to characterize the samples. The produced multifunctional nano-formulation served as an intrinsic drug delivery system, allowing for effective loading and targeting of chemotherapeutics on the Breast cancer (AMJ 13) cell line. Flowcytometry was used to assess therapy efficacy by measuring apoptotic induction.  Results: DOX and CS-Ag

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Publication Date
Thu Mar 30 2017
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
In Situ Gelling Formulation of Naproxen for Oral Sustained Delivery System

Naproxen is non-steroidal anti-inflammatory drug, which has antipyretic and anti-inflammatory effect. It is extensively bound to plasma albumin, and exhibits gastric toxicity, so it may be more efficient to deliver the drug in its sustained release dosage form and adequate blood level is achieved. Three liquid formulations with in situ gelling properties have been assessed for their potential for the oral sustained delivery of naproxen . The formulations were dilute solutions of: (a) pectin; (b) gellan gum and; (c) sodium alginate, all containing complexed calcium ion that form gels when these ions are released in the acidic environment of the stomach . The viscosity of the sols and drug release were measured, and was found to be depende

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Publication Date
Tue Jan 11 2022
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Rheological Investigation of Lipid Polymer Hybrid Nanocarriers for Oral Delivery of Felodipine (Conference Paper )#

The rheological behavior among factors that are present in Stokes law can be used to control the stability of the colloidal dispersion system. The felodipine lipid polymer hybrid nanocarriers  (LPHNs) is an interesting colloidal dispersion system that is used for rheological characteristic analysis. The LPHNs compose of polymeric components and lipids. This research aims to prepare oral felodipine LPHNs to investigate the effect of independent variables on the rheological behavior of the nanosystem. The microwave-based technique was used to prepare felodipine LPHNs (H1-H9) successfully. All the formulations enter the characterization process for particle size and PDI to ascertain the colloidal properties of the prepared nanosystem t

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Publication Date
Tue Nov 01 2022
Journal Name
Energy Reports
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Publication Date
Fri Dec 23 2022
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Preparation and in-vitro Evaluation of Secnidazole as Periodontal In-situ Gel for Treatment of Periodontal Disease

This study aims to develop a thermosensitive mucoadhesive periodontal in situ gel of secnidazole for local release of drug for treatment of periodontitis, in order to increase the drug residence time and to increase patient compliance while lowering the side effects of the drug.

Cold method was used to prepare 30 formulas of secnidazole periodontal in situ gel, using different concentrations of thermosensitive polymers (poloxamer407 alone or in combination with poloxamer 188) and methyl cellulose (MC ) or hydroxypropyl methylcellulose (HPMC K4M )in different concentrations used as mucoadhesive polymer and the resultant formulations were subjected to several tests such as   gelation temperature GT, appearance and pH value. The fo

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Publication Date
Wed Nov 01 2023
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Protective Effect of Cafestol on Doxorubicin-induced Genotoxicity in Rats
Doxorubicin is an efficient antineoplastic agent that has a broad antitumour spectrum; however, its genotoxic adverse effects on normal cells can be produced through oxidative damage, and this limits its clinical application. Cafestol is a naturally-occurring diterpene in unfiltered coffee with noteworthy antioxidant, antimutagenic and anti-inflammatory activities.

The present study aimed to investigate the possible protective effect of cafestol against doxorubicin-induced chromosomal and DNA damage in rat bone marrow cells. Wistar

Albino rats of both sexes were administered cafestol (5mg/kg body weight once

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Publication Date
Thu Jan 02 2014
Journal Name
Journal Of The Faculty Of Medicine Baghdad
Effect of doxorubicin on the histological structure of the kidneys in male albino rats

Background:  doxorubicin is one of the most active cytotoxic agents in current use, it has a very potent effect in the treatment of various malignancy either used alone or combined with other cytocidal agents, the antitumor activity of this drug associated with cytotoxic effect such as cardiotoxicity, hepatotoxicity,  nephrotoxicity, myelosuppression.

Objectives: - this study was designed to investigate the effect of the doxorubicin on the histological structure of the rats' kidney.


Results:
  -  Doxorubicin cause reduction in the body weight and changes in the histological structure of the kidney which are atrophy of some  glomeruli with

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Publication Date
Wed May 24 2017
Journal Name
Ibn Al-haitham Journal For Pure And Applied Sciences
Electrical Properties of Poly (Ethylene Oxide) polymer Doped by MnCl2

  The electrical properties of Poly (ethylene oxide)-MnCl2 Composites were studied by using the impedance technique. The study was carried out as a function of frequency in the range from 10 Hz to 13 MHz and MnCl2 salt concentration ranged from 0% to 20% by weight. It was found that the dielectric constants and the dielectric loss of the prepared films increase with the increase of the MnCl2 concentration; The A.C. conductivity increases with the increase of the applied frequency, and the MnCl2 content in the composite membrane. Relaxation processes were observed to take place for composites which have a high salt concentration. The observed relaxation and polarization effects of the composite are mainly attributed to the dielectric

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