SN-38 loading capacity of hydrophobic polymer blend nanoparticles: formulation, optimization and efficacy evaluation

Autor: Nikola Geskovski, Katerina Goracinova, Sonja Ugarkovic, Marina Chacorovska, Simona Dimchevska, Gjorgji Petruševski, Riste Popeski-Dimovski
Rok vydání: 2016
Předmět:
Drug
Materials science
Polymers
Drug Compounding
media_common.quotation_subject
Drug Evaluation
Preclinical
Pharmaceutical Science
Nanoparticle
SN-38
02 engineering and technology
Irinotecan
010402 general chemistry
01 natural sciences
law.invention
chemistry.chemical_compound
law
Cell Line
Tumor
Drug Discovery
Polymer chemistry
Animals
Humans
Particle Size
Rats
Wistar
Crystallization
Cell Proliferation
media_common
Pharmacology
chemistry.chemical_classification
Organic Chemistry
technology
industry
and agriculture
Polymer
021001 nanoscience & nanotechnology
Antineoplastic Agents
Phytogenic
Rats
0104 chemical sciences
PLGA
Treatment Outcome
Chemical engineering
chemistry
Polycaprolactone
Nanoparticles
Camptothecin
Female
Polymer blend
0210 nano-technology
Hydrophobic and Hydrophilic Interactions
DOI: 10.6084/m9.figshare.4487528
Popis: One of the most important problems in nanoencapsulation of extremely hydrophobic drugs is poor drug loading due to rapid drug crystallization outside the polymer core. The effort to use nanoprecipitation, as a simple one-step procedure with good reproducibility and FDA approved polymers like Poly(lactic-co-glycolic acid) (PLGA) and Polycaprolactone (PCL), will only potentiate this issue. Considering that drug loading is one of the key defining characteristics, in this study we attempted to examine whether the nanoparticle (NP) core composed of two hydrophobic polymers will provide increased drug loading for 7-Ethyl-10-hydroxy-camptothecin (SN-38), relative to NPs prepared using individual polymers. D-optimal design was applied to optimize PLGA/PCL ratio in the polymer blend and the mode of addition of the amphiphilic copolymer Lutrol®F127 in order to maximize SN-38 loading and obtain NPs with acceptable size for passive tumor targeting. Drug/polymer and polymer/polymer interaction analysis pointed to high degree of compatibility and miscibility among both hydrophobic polymers, providing core configuration with higher drug loading capacity. Toxicity studies outlined the biocompatibility of the blank NPs. Increased in vitro efficacy of drug-loaded NPs compared to the free drug was confirmed by growth inhibition studies using SW-480 cell line. Additionally, the optimized NP formulation showed very promising blood circulation profile with elimination half-time of 7.4 h.
Databáze: OpenAIRE
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