Paliperidone-Loaded Nanolipomer System for Sustained Delivery and Enhanced Intestinal Permeation: Superiority to Polymeric and Solid Lipid Nanoparticles

• Published in: AAPS PharmSciTech 2017-08, Vol.18 (6), p.1946-1959
• Main Authors: Helal, Hala Mahmoud, Mortada, Sana Mohamed, Sallam, Marwa Ahmed
• Format: Article
• Language: English
• Subjects: Administration, Oral; Animals; Antipsychotic Agents - administration & dosage; Antipsychotic Agents - chemistry; Antipsychotic Agents - metabolism; Biochemistry; Biomedical and Life Sciences; Biomedicine; Biotechnology; Caproates - administration & dosage; Caproates - chemistry; Caproates - metabolism; Drug Carriers - administration & dosage; Drug Carriers - chemistry; Drug Carriers - metabolism; Female; Intestinal Absorption - drug effects; Intestinal Absorption - physiology; Lactones - administration & dosage; Lactones - chemistry; Lactones - metabolism; Lipids - administration & dosage; Lipids - chemistry; Nanoparticles - administration & dosage; Nanoparticles - chemistry; Nanoparticles - metabolism; Organ Culture Techniques; Paliperidone Palmitate - administration & dosage; Paliperidone Palmitate - chemistry; Paliperidone Palmitate - metabolism; Particle Size; Pharmacology/Toxicology; Pharmacy; Polymers - administration & dosage; Polymers - chemistry; Polymers - metabolism; Rats; Rats, Wistar; Research Article
• ISSN: 1530-9932; 1530-9932
• DOI: 10.1208/s12249-016-0657-1

Paliperidone (PPD) is the most recent second-generation atypical antipsychotic approved for the treatment of schizophrenia. An immediate release dose causes extrapyramidal side effects. In this work, a novel nanolipomer carrier system for PPD with enhanced intestinal permeability and sustained release properties has been developed and optimized. PPD was successfully encapsulated into a lipomer consisting of a specific combination of biocompatible materials including poly-ε-caprolactone as a polymeric core, Lipoid S75, and Gelucire® 50/13 as a lipid shell and polyvinyl alcohol as a stabilizing agent. The lipomer system was characterized by dynamic light scattering, TEM, DSC, and FTIR. An optimized lipomer formulation possessed a particle size of 168 nm, PDI of 0.2, zeta potential of −23 mV and an encapsulation efficiency of 87.27% ± 0.098. Stability in simulated gastrointestinal fluids investigated in terms of particle size, zeta potential, and encapsulation efficiency measurements ensured the integrity of the nanoparticles upon oral administration. PPD-loaded nanolipomers demonstrated a superior sustained release behavior up to 24 h and better ex vivo intestinal permeation for PPD compared to the corresponding polymeric and solid lipid nanoparticles and drug suspension. The in vitro hemocompatibility test on red blood cells revealed no hemolytic effect of PPD-loaded lipomers which reflects its safety. The elaborated nanohybrid carrier system represents a promising candidate for enhancing the absorption of PPD providing a 2.6-fold increase in the intestinal permeation flux compared to the drug suspension while maintaining a sustained release behavior. It is a convenient alternative to the commercially available dosage form of PPD.