pectins and Brain-Neoplasms

Glioblastoma is the most common malignant tumor of the brain, but its treatment outcomes can be improved by new therapeutic techniques using biocompatible materials. Utilizing controllable alkaline de-esterification we obtained pectin preparation with 27.4% esterification degree and used it for bio-artificial matrix production. We discovered optimal gelation conditions in the presence of Ca

Topics: Animals; Biocompatible Materials; Brain Neoplasms; Cell Line, Tumor; Embryo, Mammalian; Glioblastoma; Hydrogels; Neural Stem Cells; Pectins; Rats; Rats, Wistar

Glioblastoma is a malignant brain tumour with a median survival of 14.6 months from diagnosis. Despite maximal surgical resection and concurrent chemoradiotherapy, reoccurrence is inevitable. To try combating the disease at a stage of low residual tumour burden immediately post-surgery, we propose a localised drug delivery system comprising of a spray device, bioadhesive hydrogel (pectin) and drug nanocrystals coated with polylactic acid-polyethylene glycol (NCPPs), to be administered directly into brain parenchyma adjacent to the surgical cavity. We have repurposed pectin for use within the brain, showing in vitro and in vivo biocompatibility, bio-adhesion to mammalian brain and gelling at physiological brain calcium concentrations. Etoposide and olaparib NCPPs with high drug loading have shown in vitro stability and drug release over 120 h. Pluronic F127 stabilised NCPPs to ensure successful spraying, as determined by dynamic light scattering and transmission electron microscopy. Successful delivery of Cy5-labelled NCPPs was demonstrated in a large ex vivo mammalian brain, with NCPP present in the tissue surrounding the resection cavity. Our data collectively demonstrates the pre-clinical development of a novel localised delivery device based on a sprayable hydrogel containing therapeutic NCPPs, amenable for translation to intracranial surgical resection models for the treatment of malignant brain tumours.

Topics: Adhesiveness; Aerosols; Animals; Antineoplastic Agents; Brain; Brain Neoplasms; Drug Carriers; Drug Compounding; Drug Liberation; Etoposide; Glioblastoma; Humans; Hydrogels; Lactates; Male; Mice, Nude; Nanoparticles; Pectins; Phthalazines; Piperazines; Polyethylene Glycols; Rats; Solubility; Tissue Distribution

Walker tumor cells and carcinogens were implanted into the brains of rats and L1210, P388 and Ehrlich ascites tumors, in addition to inflammatory agents and hydrocarbons, injected cortically into mice. Behavioral changes were followed in such animals by several psychological criteria, a discriminated lever-press task in rats and an exploratory task, the poke test, in rats and mice. An activity wheel was also employed for further amplification of mouse behavior. No definite changes could be discerned by these tests between rats bearing tumor or carcinogen and the respective controls as was also the case with levels of activity in the mouse. In marked contrast, mice administered tumors or kaolin cortically demonstrated significant reductions in the mean number of pokes, especially with the higher numbers of cells injected and where neurological symptoms were evident. Behavioral changes, if any, were minimal in mice with cortically implanted carcinogens.

Topics: Animals; Behavior, Animal; Brain Diseases; Brain Neoplasms; Carcinogens; Carcinoma 256, Walker; Carcinoma, Ehrlich Tumor; Cerebral Cortex; Haplorhini; Hydrocarbons; Inflammation; Kaolin; Leukemia L1210; Male; Mice; Neoplasm Transplantation; Pectins; Rats; Talc