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Targeted drug delivery for brain tumor treatment is one of the important objectives in nanomedicine. Human glioblastoma is the most frequent and aggressive type of brain tumors. The preferential expression of membrane protein connexin 43 (Cx43) and brain-specific anion transporter (BSAT1) in the tumor and peritumoral area is a key component for targeted drug delivery. The purpose of this study was to design cisplatin-loaded nanogels conjugated with monoclonal antibodies to Cx43 and BSAT1 for treatment of intracranial gliomas 101/8. MRI volumetric analysis of tumor-bearing rats indicated significantly reduced tumor volume with cisplatin-loaded targeted-nanogel treatment compared to other formulations. The median survival of rats treated with targeted nanogels conjugated with specific mAbs against extracellular loops of Cx43 and BSAT1 were 27 and 26.6 days higher than that in control group, respectively. For the first time we demonstrated the efficiency of mAb-targeted cisplatin-loaded nanogels in the experimental model of glioma 101/8. This approach could facilitate the development of new drug delivery systems for the treatment of gliomas. [ABSTRACT FROM AUTHOR]

It was recently shown that doxorubicin (DOX) bound to polysorbate-coated nanoparticles (NP) crossed the intact blood–brain barrier (BBB), and thus reached therapeutic concentrations in the brain. Here, we investigated the biodistribution in the brain and in the body of poly(butyl-2-cyano[3- 14 C]acrylate) NP ([ 14 C]-PBCA NP), polysorbate 80 (PS 80)-coated [ 14 C]-PBCA NP, DOX-loaded [ 14 C]-PBCA NP in glioblastoma 101/8-bearing rats after i.v. injection. The biodistribution profiles and brain concentrations of radiolabeled NP were determined by radioactivity counting after i.v. administration in rats. Changes in BBB permeability after tumour inoculation were assessed by i.v. injection of Evans Blue solution. The accumulation of NP in the tumour site and in the contralateral hemisphere in glioblastoma bearing-rats probably was augmented by the enhanced permeability and retention effect (EPR effect) that may have been becoming instrumental due to the impaired BBB on the NP delivery into the brain. The uptake of the NP by the organs of the reticuloendothelial system (RES) was reduced after PS 80-coating, but the addition of DOX increased again the concentration of NP in the RES. [ABSTRACT FROM AUTHOR]

Background: Doxorubicin is a well-known antitumor drug that is not employed for chemotherapy of brain tumors. Indeed, doxorubicin does not penetrate across the blood-brain barrier in therapeutic concentrations., Objective: To study the antitumor effect of doxorubicin combined with nitrosorbide on intracranial experimental glioblastoma 101/8 in rats., Material and Methods: Male Wistar rats ( n =86) with intracranial implanted glioblastoma 101/8 received doxorubicin (i.v. 1.5 mg/kg thrice) alone or in combination with nitrosorbide (i.v or orally, 0.5 mg/kg thrice) in 2, 5 and 8 days after implantation. Efficacy was assessed considering survival and brain tumor volume in 14 days after tumor implantation., Results: Combination of doxorubicin and nitrosorbide significantly increased survival (57% and 155%, respectively) and slowed down tumor growth (16±12 and 8±6 mm 3 , respectively) compared to doxorubicin alone. Effectiveness of nitrosorbide alone was trivial., Conclusion: Nitric oxide donor nitrosorbide considerably potentiated the antitumor effect of doxorubicin against intracranial 101/8 glioblastoma in rats.

The objective of this study was to investigate the therapeutic effects of doxorubicin bound to polysorbate-coated nanoparticles that had previously been shown to significantly enhance survival in the orthotopic rat 101/8 glioblastoma model. Tumor-bearing animals were subjected to chemotherapy using doxorubicin in solution (Dox-sol) or doxorubicin bound to polysorbate 80-coated poly(butyl cyanoacrylate) nanoparticles (Dox-np) injected intravenously on Days 2, 5 and 8 post tumor implantation. The antitumor effect was assessed on Days 10, 14 and 18 post tumor implantation. Tumors showed signs of malignancy including invasion of brain tissue, brisk mitotic activity, microvascular proliferation, necrosis and increased proliferation resembling human glioblastoma. Dox-np produced a considerably more pronounced antitumor effect exhibited as a reduced tumor size, lower proliferation, and a decreased necrotic area compared to Dox-sol and to untreated control groups. A drastic effect of Dox-np on vascularization indicated an antiangiogenic mode of action.

The effects of 16α, 17α -cyclohexanodihydroprogesterone, the structural analogues of the closest progesterone metabolites (4,5-dihy-droprogesterones) on the uterine tissues of intact, impregnated, and pseudopregnant rats has demonstrated that they cause uterine epithelial destruction. This effect does not affect the rate and completeness of fetal implantation, but it may play a role during labor, by facilitating fetal rejection. Earlier studies have indicated that the above analogues of the metabolites of progesterone eliminate the latter-induced oxytocin receptor blockade and cause myometrial destruction in pseudopregnant animals. These facts suggest that by accumulating by the end of pregnancy, the natural progesterone metabolites (4.5-dihydroprogesterones) can act as trigger compounds - "labor hormones".

Neurochordins are a family of high Mr P-epitope-bearing neural tissue glycoproteins. Comparison of SDS-agarose electrophoretic patterns of extracts from human, rat, mouse and chicken brain after immunostaining of blots with an anti-P-epitope MAb At5 demonstrated that in each case neurochordins from the A, B and C group were present. A similar result was obtained when polyclonal serum against total human neurochordin was used. The data favours the idea of high evolutional conservatism of neurochordins of higher vertebrate species. Expression of the P-epitope on glial cells in culture was studied. Strong immunostaining of oligodendrocytes with MAb At5 and the absence of this staining in astrocytes and Schwann cells make it possible to use At5 for identification of cell types in tissue culture experiments as well as for differential diagnostics of brain tumours.