ABSTRACT
A series of novel reduction-responsive micelles with tailored size were designed and prepared to release doxorubicin (DOX) for treating glioma, which were developed based on amphiphilic block copolymer poly (2-ethyl-2-oxazoline)-b-poly (ε-caprolactone) (PEtOz-SS-PCL) and the micelle size could be regulated by designing the polymer structure. The DOX-loaded PEtOz-SS-PCL micelles had small size and rapid drug release in reductive intracellular environments. Biodistribution and in vivo imaging studies in C6 glioma mice tumor model showed that DOX loaded PEtOz-SS-PCL43 micelles with the smallest size had superior accumulation and fast drug release in tumor sites. In vivo antitumor activity demonstrated that DOX-loaded PEtOz-SS-PCL43 micelles improved antitumor efficacy in contrast to PEtOz-SS-PCL micelles with larger size toward the orthotopic C6-Luci cells-bearing mice. This study shows great potential in tailoring the micelle size and introducing the responsive bonds or compartment for intracellular drug delivery and release in glioma treatment by designing the architecture of the polymer.
Subject(s)
Antineoplastic Agents/chemistry , Caproates/chemistry , Doxorubicin/chemistry , Doxorubicin/pharmacology , Glioma/drug therapy , Lactones/chemistry , Oxazoles/chemistry , Animals , Antineoplastic Agents/pharmacology , Biological Transport/physiology , Blood-Brain Barrier/metabolism , Cell Survival/drug effects , Drug Carriers/chemistry , Drug Delivery Systems/methods , Drug Liberation/physiology , Male , Mice , Mice, Inbred ICR , Micelles , Particle Size , Polymers/chemistry , Tissue Distribution/physiologyABSTRACT
Objective To explore the feasibility and operation methods of interforniceal diaterma keyhole approach for operative therapy of apex basilar artery aneurysm. Methods Interforniceal diaterma keyhole approach was designed to interpeduncular cistern with diaterma incision from tuber cinereum to posterior perforated substance and between bilateral mammillary bodies. The simulation operations of interforniceal diaterma keyhole approach were performed in 16 cadaveric heads by assisting with Stryker neuronavigation. Anatomic structures were observed by surgical microscope and measured by Stryker neuronavigation in the keyhole approach operations. Results The operations of interforniceal diaterma keyhole approach could be accomplished successfully in 16 cadaveric heads. The distances from bregma to superior margin of interventricular foramen, superior margin of adhaesio interthalamica, mammillary body, superior margin of aqueduct of midbrain and bifurcation of basilar artery were (68.4±4.6)mm, (66.3±6.0)mm,(86.3±5.3)mm, (82.0±7.6)mm and (91.8±5.0)mm respectively. The length of surgical window of diaterma was (9.5±2.6)mm from tuber cinereum to posterior perforated substance between bilateral mamillary bodies. The apex of basilar artery, P1 and P2 of posterior cerebral artery, superior cerebellar artery, posterior communicating artery and perforating branches from them could be exposed distinctly in interpeduncular cistern. The scope of operative exposure region was front to clivus and dorsum sellae by dissected the Liliequist panniculus, lateral to oculomotor nerve and posterior to interpeduncular fossa. The bifurcation of basilar artery apex was deviation to left in 68.8%. The bilateral posterior cerebral arteries were oblique to the anterolateral in 68.8%. There were 1-4 perforating branches from the apex of basilar artery in the included angle of bilateral posterior cerebral arteries. Conclusion Interforniceal diaterma keyhole approach is feasible for technique. It is worth of implementing and perfecting in surgical therapy of the apex basilar artery aneurysm.
