Nanoparticles containing anti-inflammatory agents as chemotherapy adjuvants: optimization and in vitro characterization.
The pre-administration of dexamethasone (DEX) has previously been shown to enhance the anti-tumor efficacy of chemotherapeutic agents. The delivery of anti-inflammatory agents specifically to tumors via nanoparticle carriers is expected to promote the effectiveness of chemotherapeutic agents while avoiding systemic toxicities. The process for preparing solid lipid nanoparticles containing anti-inflammatory agents using the nanotemplate engineering method was optimized. Due to the solubilization of DEX in the bulk aqueous phase, its more lipophilic palmitate ester was synthesized and incorporated in nanoparticles that included a pegylating agent, PEG6000 mono-stearate, as part of the formulation. The stealth properties of these nanoparticles were demonstrated to be enhanced compared to latex particles by measuring the adsorption of radioiodinated IgG (185 microg vs. 6.7 microg IgG/mg NP). In addition, the uptake of (14)C-labeled nanoparticles by murine macrophages was shown to decrease from 36.6% to 14.7% of the nanoparticles/mg cell protein as the amount of pegylating agent in the formulation increased from 0 to 4 mg/mL. The high loading values and low burst effect observed for these DEX palmitate-containing nanoparticles in addition to their stealth properties are expected to allow for the delivery of sufficient amounts of DEX to tumors to enhance the uptake of chemotherapeutic agents.
Lu
Xiuling
X
Department of Pharmaceutical Sciences, University of Kentucky, Lexington, Kentucky 40536-0082, USA. xiuling.lu@uky.edu
Howard
Melissa D
MD
Mazik
Marta
M
Eldridge
Joshua
J
Rinehart
John J
JJ
Jay
Michael
M
Leggas
Markos
M
D000277:Adjuvants, Pharmaceutic / Q000008:administration & dosage / Q000737:chemistry*; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry*; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D010316:Particle Size
D000277:Adjuvants, Pharmaceutic; D000893:Anti-Inflammatory Agents; D000970:Antineoplastic Agents; D004337:Drug Carriers