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Abstract
Poly(n-butyl cyanoacrylate) nanoparticles coated with polysorbate-80 can enable the transport of bound drugs across the blood–brain barrier (BBB) after i.v. injection. In the present study the influence of different formulation parameters on the anti-tumoural effects of doxorubicin nanoparticles against glioblastoma 101/8 was investigated. The manufacturing parameters of poly(alkyl cyanoacrylate) doxorubicin-loaded nanoparticles were optimized concerning drug loading. The nanoparticles were coated with different surfactants and injected intravenously on days 2, 5 and 8 after intra-cranial implantation of glioblastoma 101/8 to rats. The survival times of all doxorubicin containing preparations, including a doxorubicin solution, increased the survival times significantly compared to untreated tumour-bearing rats. The most pronounced increase in survival was obtained with the poly(n-butyl cyanoacrylate) doxorubicin-loaded nanoparticles coated with polysorbate 80 and 35% of these animals survived for over 180 days (termination of the experiments). The other nanoparticle preparations yielded lower survival times. Poly(n-butyl cyanoacrylate) doxorubicin-loaded nanoparticles coated with polysorbate 80-coated proved to be very efficient against glioblastoma 101/8. The data suggest that the interaction of nanoparticles with the blood after injection as well as the enhanced permeability and retention effect (EPR effect) contributed differently to the anti-tumoural efficacy depending on nanoparticle formulation and surface properties.
| Abbreviations | ||
| CNS | = | central nervous system |
| BBB | = | blood–brain barrier |
| ABC | = | ATP-binding cassette |
| P-gp | = | P-glycoprotein efflux system |
| n-BCA | = | normal-butyl cyanoacrylate |
| iso-BCA | = | iso-butyl cyanoacrylate |
| NP | = | nanoparticles |
| PBCA | = | poly(butyl cyanoacrylate) |
| DOX | = | doxorubicin |
| PS 80 | = | polysorbate 80 |
| AUC | = | area under the curve. |
| Abbreviations | ||
| CNS | = | central nervous system |
| BBB | = | blood–brain barrier |
| ABC | = | ATP-binding cassette |
| P-gp | = | P-glycoprotein efflux system |
| n-BCA | = | normal-butyl cyanoacrylate |
| iso-BCA | = | iso-butyl cyanoacrylate |
| NP | = | nanoparticles |
| PBCA | = | poly(butyl cyanoacrylate) |
| DOX | = | doxorubicin |
| PS 80 | = | polysorbate 80 |
| AUC | = | area under the curve. |