Double-Controlled Release of Poorly Water-Soluble Paliperidone Palmitate from Self-Assembled Albumin-Oleic Acid Nanoparticles in PLGA in situ Forming Implant

Purpose: To investigate the effects of solvents on the formation of self-assembled nanonization of albumin-oleic acid conjugates (AOCs) using a solvent exchange mechanism for the construction of in situ forming implants (ISFI). Methods: A poorly water-soluble drug, paliperidone palmitate (PPP), was chosen as the model drug. AOC was synthesized with the 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) reaction. Dichloromethane, tetrahydrofuran, ethanol, N-methyl-2-pyrrolidone, dimethyl sulfoxide, and deionized water were selected to investigate the formation of self-assembled AOC nanoparticles (AONs). The volume ratios of organic solvents against water could determine the miscibility, injectability, and in situ nanonizing capability without aggregation. Results: As the polarity of the organic solvents increased, the AONs exhibited a spherical shape, and the larger the volume of the solvent, the smaller the size of the AONs. To use AOC in ISFI for controlled release of PPP, poly(d,l-lactide-co-glycolide) (PLGA) was combined with the AOC in 2 mL of N-methyl-2-pyrrolidone and water solution (1.8/0.2 ratio). The release rates of all formulations exhibited similar curve patterns overall but were more controlled in decreasing order as follows: AOC, PLGA, and AOC/PLGA for 14 days. Conclusion: A combined formulation of AOC and PLGA was found to effectively control the initial burst release of the drug.

Automated summary

This study aimed to investigate the effects of solvents on the formation of self-assembled albumin-oleic acid conjugate nanoparticles and construct in situ forming implants. The results showed that with increasing polarity of the organic solvents, the AONs exhibited a spherical shape, and larger solvent volumes resulted in smaller AON sizes.