Biocompatibility, efficacy and biodistribution of Gelucire-stabilized nanoparticles engineered for docetaxel delivery.
*Biocompatible Materials; *Nanoparticles; Animals; Antineoplastic Agents/*administration & dosage/pharmacokinetics/pharmacology; Docetaxel; Macrophage Activation/drug effects; Platelet Aggregation/drug effects; Rats; Reactive Oxygen Species/metabolism; Taxoids/*administration & dosage/pharmacokinetics/pharmacology; Tissue Distribution
Docetaxel is a potent anticancer agent that will benefit greatly from alternative delivery systems that can overcome several reported adverse effects due to the drug itself and/or the solvent system in the current clinical formulation. In this regard, a new nanoparticle delivery system for docetaxel was prepared from Gelucire-based nanoemulsions by using binary mixtures of Gelucire 44/14 and cetyl alcohol as NP matrix materials. Various amounts of docetaxel (50-1000 microg/ml) were added to the oil phase of the nanoemulsions prior to obtaining solid nanoparticles. The nanoparticles (100-140 nm) achieved high entrapment efficiency (\textgreater or = 89%) of docetaxel which was maintained upon storage at 4 degrees C and 25 degrees C. Additional data indicated the Gelucire component in NP played influential roles in drug release possibly by facilitating diffusion from NPs and/or accelerating erosion of NP matrix. Docetaxel-loaded nanoparticles did not cause any significant red blood cell lysis or platelet aggregation nor activate macrophages. Also in-vitro antitumor efficacy in human lung adenocarcinoma cells was demonstrated based on cell cytotoxicity, production of reactive oxygen species and reduction of mitochondrial potential. Enhancement of in-vitro antitumor effects of docetaxel with Gelucire-based NPs could be ascribed to improved particle dispersion and efficient cell permeability. Studies in BALB/c mice demonstrated the stability/retention of NPs in blood circulation and the potential in facilitating docetaxel absorption across the peritoneal cavity. The nanoparticles reported herein may be effective as novel biocompatible and effective delivery systems for docetaxel.
Wehrung Daniel; Geldenhuys Werner J; Bi Lipeng; Oyewumi Moses O
Journal of nanoscience and nanotechnology
2012
2012-03
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1166/jnn.2012.5789" target="_blank" rel="noreferrer noopener">10.1166/jnn.2012.5789</a>
Engineering Alkoxyphenacyl-Polycarbonate Nanoparticles for Potential Application in Near-Infrared Light-Modulated Drug Delivery via Photon Up-Conversion Process
800 nm; alkoxylphenacyl-based polycarbonates; biocompatibility; Chemistry; Doxorubicin; Drug Release; luminescence; Materials Science; mesoporous-silica; nanocrystals; Nanotechnology; Near-Infrared Light; photodynamic therapy; Physics; release; Science & Technology - Other Topics; Stimuli-Responsive; upconverting nanoparticles; uv
Photoresponsive delivery systems that are activated by high energy photo-triggers have been accorded much attention because of the capability to achieve reliable photoreactions at short irradiation times. However, the application of a high energy photo-trigger (UV light) is not clinically viable. Meanwhile, the process of photon-upconversion is an effective strategy to generate a high energy photo-trigger (in-situ) through exposure to clinically relevant near-infrared (NIR) light. In this regard, we synthesized photon upconverting nanocrystals (UCNCs) that were subsequently loaded into photoresponsive nanoparticles (NPs) that were prepared using alkoxyphenacyl-based polycarbonate homopolymer (UCNC-APP-NPs). UCNC loading affected resultant NP size, size distribution, colloidal stability but not the zeta potential. The efficiency of NIR-modulated drug delivery was impacted by the heterogenetic nature of the resultant UCNC-APP-NPs which was plausibly formed through a combination of UCNC entrapment within the polymeric NP matrix and nucleation of polymer coating on the surface of the UCNCs. The biocompatibility of UCNC-APP-NPs was demonstrated through cytotoxicity, macrophage activation, and red blood cell lysis assays. Studies in tumor-bearing (nu/nu) athymic mice showed a negligible distribution of UCNC-APP-NPs to reticuloendothelial tissues. Further, distribution of UCNC-APP-NPs to various tissues was in the order (highest to lowest): Lungs> Tumor > Kidneys > Liver > Spleen> Brain > Blood > Heart. In all, the work highlighted some important factors that may influence the effectiveness, reproducibility and biocompatibility of drug delivery systems that operate on the process of photon-upconversion.
Wehrung D; Chamsaz E A; Andrews J H; Joy A; Oyewumi M O
Journal of Nanoscience and Nanotechnology
2017
2017-07
Journal Article
<a href="http://doi.org/10.1166/jnn.2017.13449" target="_blank" rel="noreferrer noopener">10.1166/jnn.2017.13449</a>