Journal
BIOMATERIALS
Volume 28, Issue 5, Pages 869-876Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2006.09.047
Keywords
drug delivery; nanoparticle; PLGA; prostate cancer; targeting; aptamer
Funding
- NCI NIH HHS [CA 119349, U54 CA119349-02, U54 CA119349, U54 CA119349-01] Funding Source: Medline
- NIBIB NIH HHS [K08 EB003647-01A1, K08 EB003647, K08 EB003647-02, EB 003647] Funding Source: Medline
Ask authors/readers for more resources
Nanoparticle (NP) size has been shown to significantly affect the biodistribution of targeted and non-targeted NPs in an organ specific manner. Herein we have developed NPs from carboxy-terminated poly(D,L-lactide-co-glycolide)-block-poly(ethylene glycol) (PLGA-b-PEG-COOH) polymer and studied the effects of altering the following formulation parameters on the size of NPs: (1) polymer concentration, (2) drug loading, (3) water miscibility of solvent, and (4) the ratio of water to solvent. We found that NP mean volumetric size correlates linearly with polymer concentration for NPs between 70 and 250 nm in diameter (linear coefficient = 0.99 for NPs formulated with solvents studied). NPs with desirable size, drug loading, and polydispersity were conjugated to the A10 RNA aptamer (Apt) that binds to the prostate specific membrane antigen (PSMA), and NP and NP-Apt biodistribution was evaluated in a LNCaP (PSMA+) xenograft mouse model of prostate cancer. The surface functionalization of NPs with the A10 PSMA Apt significantly enhanced delivery of NPs to tumors vs. equivalent NPs lacking the A10 PSMA Apt (a 3.77-fold increase at 24 h; NP-Apt 0.83% +/- 0.21% vs. NP 0.22% +/- 0.07% of injected dose per grain of tissue; mean +/- SD, n = 4, p = 0.002). The ability to control NP size together with targeted delivery may result in favorable biodistribution and development of clinically relevant targeted therapies. (c) 2006 Elsevier Ltd. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available