Methotrexate loading in chitosan nanoparticles at a novel pH: Response surface modeling, optimization and...

Area of Science:

• Nanotechnology
• Materials Science
• Pharmaceutical Sciences

Background:

• Chitosan-tripolyphosphate nanoparticles (Cs-TPP NPs) are promising drug delivery vehicles.
• Encapsulating anionic drugs like methotrexate (MTX) into Cs-TPP NPs presents formulation challenges, particularly at specific pH values.

Purpose of the Study:

• To evaluate the feasibility of encapsulating methotrexate (MTX) into chitosan (Cs)-tripolyphosphate nanoparticles (NPs) at a critical formulation pH of 6.2.
• To optimize the formulation parameters for high drug entrapment efficiency (EE%) and desired nanoparticle characteristics.

Main Methods:

• Response surface methodology with a three-level full factorial design was employed.
• Investigated the effects of chitosan concentration and MTX concentration on EE%, particle size (PS), polydispersity index (PDI), and zeta potential (ZP).
• Utilized the desirability function approach for simultaneous optimization of multiple responses.

Main Results:

• Successfully prepared MTX-loaded Cs-TPP NPs at pH 6.2.
• Developed significant quadratic models for EE%, PS, and ZP, and a 2-factor interaction model for PDI.
• Achieved maximum global desirability (D=0.856) at high Cs and MTX concentrations, resulting in 73.38% EE%, 232.6nm PS, 0.195 PDI, and +18.4mV ZP.

Conclusions:

• The novel formulation pH of 6.2 is feasible for developing MTX-loaded Cs-TPP NPs.
• Optimized conditions enable the production of highly efficient, stable, and well-characterized nanoparticles for drug delivery applications.