Long-Acting Paliperidone Parenteral Formulations Based on Polycaprolactone Nanoparticles; the Influence of Stabilizer and Chitosan on In Vitro Release, Protein Adsorption, and Cytotoxicity

Abstract

Long-acting preparations containing the antipsychotic paliperidone for intramuscular injection has drawn considerable attention to achieve harmless long-term treatment. This study aimed to develop paliperidone loaded polycaprolactone (PCL) nanoparticles and investigate the influence of PCL/drug ratio, stabilizer type, and chitosan coating on physicochemical properties, protein adsorption, and cellular toxicity. Results showed that chitosan coating produced enlarged particle sizes, shifted the surface charges from negative into positive and did not influence encapsulation efficiencies. Chitosan coating relatively sustained the drug release especially in pluronic stabilized formulations. Pluronic F127 based formulations exhibited the least protein adsorption (384.3 μg/mL). Chitosan coating of Tween 80 and polyvinyl alcohol stabilized formulations significantly (p < 0.05) increased protein adsorption. Cellular viability was concentration-dependent and negatively affected by stabilizers. All formulations did not show cellular death at 1.56 μg/mL. Inflammatory responses and oxidative stress were less affected by Tween 80 compared with other stabilizers. Chitosan minimized all aspects of cellular toxicity. Collectively, stabilizer type and chitosan coating play critical roles in developing safe and effective long-acting PCL nanoparticles intended for parenteral drug delivery. The coated formulations containing Tween 80 and Pluronic F127 as stabilizers are warranted a future in vivo study to delineate its safety and efficacy profiles.

The efficacy of Origanum majorana nanocubosomal systems in ameliorating submandibular salivary gland alterations in streptozotocin-induced diabetic rats

“…Similar results were formerly observed by Elmowafy et al. ( 2020 ). It was previously reported that the molecular weight, structure, and conformation of surfactants play a crucial role in determining the surface charge carried by the formulated vesicles, even with nonionic surfactants that act through steric stabilization (Kovacevic et al., 2011 ).…”

Nanosystems for the Encapsulation of Natural Products: The Case of Chitosan Biopolymer as a Matrix

“…On the other hand, it should be mentioned, that negatively or neutrally charged nanoparticles prefer to co-localize with lysosomes [ 190 ]. Moreover, due to this higher extent of internalization it has been investigated that the highly positively charged chitosan enhances the cytotoxicity of various drug-loaded nanoparticles against different types of human cancer cell lines [ 189 , 191 ].…”

Olive Oil/Pluronic Oleogels for Skin Delivery of Quercetin: In Vitro Characterization and Ex Vivo Skin Permeability

“…Olive oil spectrum showed strong band absorption peaks at 2920 cm −1 and 2854 cm −1 (revealing C–H stretching vibration of methylene and methyl groups respectively), 1741 cm −1 (revealing carbonyl double bond stretching vibration) [ 44 ]. Pluronic F127 spectrum exhibited at 2824 cm −1 (revealing C-H stretching), 1281 cm −1 and 1239 cm −1 (revealing the stretching of C–O–C bonds) and 1105 cm −1 , (revealing C-O stretching) [ 45 ]. In the spectra of F1 and F4, they presented similarly except for the appearance of new peaks in F4 spectrum at 2920 cm −1 and 1753 cm −1 correspond to the typical stretching vibrations of olive oil (dashed lines).…”