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.
The protective effect of ginger extract against cisplatin-induced hepatotoxicity and cardiotoxicity was evaluated in 30 albino white rats(weighing 200-300 gm ) classified into 5groups (6 rats per each group). The rats were treated with 0.5g/kg/day or 1g/kg/day ginger extract orally 5 successive days before and 5 successive days after induction of toxicity with intraperitoneal (IP) injection of (10mg/kg ) cisplatin, resulted in a significant reduction in the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) , total serum billirubin(TSB) , lactate dehydrogenase (LDH) and creatine kinase(CK) enzymes in comparison with the cisplatin treated animals; ginger extract
... Show MoreCiprofloxacin, which is a second generation of fluoroquinolone and one of the most effective and widely used drugs within fluoroquinolone. Unfamiliar adverse effects of ciprofloxacin such as bone marrow (BM) suppression, thrombocytopenia, anemia, agranulocytosis, renal failure, and others observed. Lutein, is a xanthophyll (an oxygenated carotenoid), was focused by most studies as it has a strong antioxidant activity in vitro; and also, it has been associated with reducing the risk of the age-related disorders. The current study was designed to describe the role of apoptosis through the measurement of Bcl-2 associated X protein (Bax) marker, as mechanisms of bone marrow toxicity induced by ciprofloxacin and to find whether lutei
... Show MoreBilastine (BL) is a novel non-sedating second-generation antihistamine, and its bioavailability is about 60%. Objective: To compare the bioavailability of prepared oral self-nanoemulsions of BL (BL-SNE) with that of pure BL and marketed tablets. Methods: Four groups of Wistar rats were used in this study, each with six rats weighing between 200 and 250 g. They were treated orally using a a gavage tube. The groups were fed either with conventional tablets ("Alerbix®") after being ground and dispersed with deionized water (DIW), treated with BL-SNE or fed with pure BL powder suspension. The fourth group did not receive any medication. The concentration of BL in the rat’s plasma was measured using HPLC. We used Trandolapril as an an interna
... Show MoreFlavonoids are known to play a vital role in the management of various liver disorders.They are a large family of compounds synthesized by plants; they belong to a group of natural substances with variable phenolic structures. In this study we aim to scan the types of flavonoids in a newly studied, wild Iraqi plant named Echinops tenuisectus of Compositae family. The medicinal importance of flavonoids on one hand, and the absence of any phytochemical investigation on tenuisectus species of Echinops genus on the other hand, acquired this study itÛ¥s importance. Three flavonoids were identified in the seed,s extract of this plant (Silymarin, Rutin, Quercetin ) by two chromatographic methods, first Thin laye
... Show MoreCardiac toxicity can occur during the therapy with several cytotoxic drugs, including 5- Fluorouracil (5- FU). It is an antimetabolite that acts during the S phase of the cell cycle and is activated by thymidine phosphorylase into fluorodeoxyuridylate (5 fluoro 2'deoxyuridine 5'monophosphate, 5-FdUMP) that inhibits thymidylate synthase, thus preventing DNA synthesis that leads to imbalanced cell growth and ultimately cell death. It is still a widely used anticancer drug, since 1957. The present study aimed to evaluate the possible cardio-protective effects of ethanolic artichoke extract (Cynara scolymus L.) against 5-fluorouracil (5-FU) induced cardio-toxicity in rats by evaluating serum levels of Alanine aminotransferase, aspartate amin
... Show MoreCyclophosphamide (CP) is a cytotoxic alkylating agent it's used associated with different side effects including lung toxicity. Vitamin B2 and vitamin B12 have lung-protective effects. This study was designed to evaluate lung-protective effects of both vitamins against lung toxicity induced by cyclophosphamide. seventy healthy adult albino male and female rats divided into seven groups each group containing ten rats were used in the present study and treated for seven days. On day eight rats were sacrificed and serum was obtained for glutathione and total antioxidant capacity measurement and lung extracted for immunohistochemical study; both vitamins significantly (P<0.05) increased glutathione and total antioxidant capacity in compar
... Show MoreLasmiditan (LAS) is a recently developed antimigraine drug and was approved in October, 2019 for the treatment of acute migraines; however, it suffers from low oral bioavailability, which is around 40%.
This study aimed to improve the LAS bioavailability via formulation as nanoemulsionbased in situ gel (NEIG) given intranasally and then compare the traditional aqueous-LASsuspension (AQS) with the two successful intranasal prepared formulations (NEIG 2 and NEIG 5) in order to determine its relative bioavailability (F-relative) via using rabbits.
Background: Dolutegravir sodium (DTG), used to treat HIV, faces challenges in delivering effective therapeutic concentrations to the brain due to the blood-brain barrier (BBB). Nanostructured lipid carriers (NLCs) combined with in situ gels present a promising strategy for enhancing brain drug delivery via the intranasal route. Objective: To compare brain pharmacokinetics of DTGs delivered via NLC-loaded in situ gel intranasal administration with the conventional intravenous (IV) drug solution. Methods: 80 Wistar rats, which were divided into three groups: two groups consisting of 39 animals each and a control group with 2 animals. Rats were administered with a dose of 1.0 mg/kg of DTGs IV, and DTGs NLC-loaded in situ gel were admin
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