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Ionically fixed polymeric nanoparticles as a novel drug carrier
- Source :
- Pharmaceutical research. 24(8)
- Publication Year :
- 2006
-
Abstract
- In this study, we have prepared a novel polymeric drug delivery system comprised of ionically fixed polymeric nanoparticles (IFPN) and investigated their potential as a drug carrier for the passive targeting of water-insoluble anticancer drugs.For this purpose, the physicochemical characteristics of the IFPN were investigated by comparing them with conventional polymeric micelles. IFPN containing paclitaxel were prepared and evaluated for in vitro stability and in vivo pharmacokinetics.The IFPN were successfully fabricated using a monomethoxypolyethylene glycol-polylactide (mPEG-PLA) diblock copolymer and a sodium salt of D,L-poly(lactic acid) (D,L-PLACOONa) upon the addition of CaCl2. The transmittance of the IFPN solution was much lower than that of a polymeric micelle solution at the same polymer concentration implicating an increase in the number of appreciable particles. The particle size of the IFPN was approximately 20 approximately 30 nm which is in the range of particle sizes that facilitate sterile filtration using a membrane filter. The IFPN also have a regular spherical shape with a narrow size distribution. The zeta potential of the IFPN was almost neutral, similar to that of the polymeric micelles. In contrast, mixed micelles with a combination of mPEG-PLA and D,L-PLACOONa prior to the addition of Ca2+ showed a negative charge (-17 mV), possibly due to the carboxyl anion of polylactic acid exposed on the surface of the micelles. The IFPN formulation was highly kinetically stable in aqueous medium compared to the polymeric micelle formulation. The molecular weight of D,L-PLACOONa in the IFPN and the mPEG-PLA/D,L-PLACOONa molar ratio had a great influence upon the kinetic stability of the IFPN. Pharmacokinetic studies showed that the area under the concentration vs time curve (AUC) of IFPN in blood was statistically higher (about two times) when compared with that of Cremophor EL-based formulation (Taxol equivalent) or polymeric micelle formulation.The results suggests that the IFPN were retained in the circulation long enough to play a significant role as a drug carrier in the bloodstream, possibly resulting in improved therapeutic efficiency. Therefore, the IFPN are expected to be a promising novel polymeric nanoparticulate system for passive tumor targeting of water-insoluble anticancer drugs including paclitaxel.
- Subjects :
- Glycerol
Materials science
Paclitaxel
Polymers
Polyesters
Static Electricity
Pharmaceutical Science
Nanoparticle
Nanotechnology
macromolecular substances
Polyethylene Glycols
Rats, Sprague-Dawley
Calcium Chloride
Drug Stability
Polymeric drug
Organic chemistry
Animals
Pharmacology (medical)
Lactic Acid
Microparticle
Particle Size
Pharmacology
chemistry.chemical_classification
Drug Carriers
Organic Chemistry
technology, industry, and agriculture
Polymer
Polymeric nanoparticles
Antineoplastic Agents, Phytogenic
Rats
Polyester
Molecular Weight
chemistry
Spectrophotometry
Area Under Curve
Injections, Intravenous
Molecular Medicine
Nanoparticles
Delivery system
Drug carrier
Biotechnology
Subjects
Details
- ISSN :
- 07248741
- Volume :
- 24
- Issue :
- 8
- Database :
- OpenAIRE
- Journal :
- Pharmaceutical research
- Accession number :
- edsair.doi.dedup.....70247709a6fe6900d900ccfd317f6927