Document Detail


Effect of Size on the Biodistribution and Blood Clearance of Etoposide-Loaded PLGA Nanoparticles.
MedLine Citation:
PMID:  21502074     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
Approaches used to avoid uptake of the injected particles by the reticuloendothelial system include modification of the particle properties such as surface charge and particle size. In the present study the effect of mean particle size of etoposide-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) of sizes 105 nm ((99m)Tc-Eto-PLGA NP(105)) and 160 nm ((99m)Tc-Eto-PLGA NP(160)) on biodistribution and blood clearance were studied after intravenous administration of the radiolabeled formulations and compared to that of free drug ((99m)Tc-Eto). It was found that etoposide-loaded PLGA NPs of size 105 nm were present in the blood at higher concentrations up to 24 h and were able to reduce their uptake by the reticuloendothelial system as compared to that of etoposide-loaded PLGA NPs of size 160 nm and pure drug. Moreover, the pure drug ((99m)Tc-Eto) did not cross the blood-brain barrier, whereas (99m)Tc-Eto-PLGA NP(105) showed relatively high concentrations of 0.58% of injected dose in brain in 1 h (8-fold higher), 0.6% in 4 h (20-fold higher) and 0.22% in 24 h (10-fold higher) than the concentration of (99m)Tc-Eto-PLGA NP(160). In bone, concentration of (99m)Tc-Eto-PLGA NP(105) was about 7.2 times higher than the concentration of (99m)Tc-Eto in 24 h. The study concludes that NPs of size ∼100 nm can be used for long-term circulation without the need for surface modification. Such NPs could be exploited for use in leukemia therapy for providing sustained release of etoposide by long-term circulation. LAY ABSTRACT: Approaches used to avoid uptake of the injected particles by the reticuloendothelial system include modification of the particle properties such as surface charge and particle size. In the present study the effect of mean particle size of etoposide-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) of sizes 105 nm and 160 nm on biodistribution studies after intravenous administration in mice and blood clearance studies after intravenous administration in rats was studied. It was found that etoposide-loaded PLGA-NPs of size 105 nm were present in the blood at higher concentrations up to 24 h and were able to reduce their uptake by the reticuloendothelial system as compared to that of etoposide-loaded PLGA-NP of size 160 nm and pure drug. Moreover, the NPs of size 105 nm had greater uptake in bone and brain, in which concentration of free drug and NPs of size 160 nm was negligible. The study concludes that NPs of size ∼100 nm can be used for long-term circulation without the need for surface modification.
Authors:
Khushwant S Yadav; Krishna Chuttani; Anil K Mishra; Krutika K Sawant
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  PDA journal of pharmaceutical science and technology / PDA     Volume:  65     ISSN:  1079-7440     ISO Abbreviation:  PDA J Pharm Sci Technol     Publication Date:    2011 Mar-Apr
Date Detail:
Created Date:  2011-04-19     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9439538     Medline TA:  PDA J Pharm Sci Technol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  131-9     Citation Subset:  IM    
Affiliation:
TIFAC-Centre of Relevance and Excellence in NDDS, Pharmacy Department, The M. S. University of Baroda, Fatehgunj, Vadodara, Gujarat, India.
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