Long-Lasting, Antinociceptive Effects of pH-Sensitive Niosomes Loaded with Ibuprofen in Acute and Chronic Models of Pain

Francesca Marzoli; Carlotta Marianecci; Federica Rinaldi; Daniele Passeri; Marco Rossi; Paola Minosi; Maria Carafa; Stefano Pieretti

doi:10.3390/pharmaceutics11020062

Long-Lasting, Antinociceptive Effects of pH-Sensitive Niosomes Loaded with Ibuprofen in Acute and Chronic Models of Pain

Pharmaceutics. 2019 Feb 1;11(2):62. doi: 10.3390/pharmaceutics11020062.

Authors

Francesca Marzoli¹, Carlotta Marianecci², Federica Rinaldi³, Daniele Passeri⁴, Marco Rossi^{5

6}, Paola Minosi⁷, Maria Carafa⁸, Stefano Pieretti⁹

Affiliations

¹ Istituto Superiore di Sanità, National Center for Drug Research and Evaluation, 00161 Rome, Italy. francesca.marzoli@iss.it.
² Department of Drug Chemistry and Technology, Sapienza University of Rome, 00185 Rome, Italy. carlotta.marianecci@uniroma1.it.
³ Center for Life Nano Science@Sapienza, Istituto Italiano di Tecnologia (ITT), 00161 Rome, Italy. federica.rinaldi@uniroma1.it.
⁴ Department of Basic and Applied Sciences for Engineering, Sapienza University of Rome, 00161 Rome, Italy. daniele.passeri@uniroma1.it.
⁵ Department of Basic and Applied Sciences for Engineering, Sapienza University of Rome, 00161 Rome, Italy. marco.rossi@uniroma1.it.
⁶ Research Center for Nanotechnology Applied to Engineering, Sapienza University of Rome (CNIS), 00185 Rome, Italy. marco.rossi@uniroma1.it.
⁷ Istituto Superiore di Sanità, National Center for Drug Research and Evaluation, 00161 Rome, Italy. paola.minosi@iss.it.
⁸ Department of Drug Chemistry and Technology, Sapienza University of Rome, 00185 Rome, Italy. maria.carafa@uniroma1.it.
⁹ Istituto Superiore di Sanità, National Center for Drug Research and Evaluation, 00161 Rome, Italy. stefano.pieretti@iss.it.

Abstract

Ibuprofen is one of the non-steroidal anti-inflammatory drugs (NSAIDs) widely used to treat pain conditions. NSAIDs encounter several obstacles to passing across biological membranes. To overcome these constraints, we decided to study the effects of a new pH-sensitive formulation of niosomes containing Polysorbate 20 derivatized by Glycine and loaded with ibuprofen (NioIbu) in several animal models of pain in mice. We performed two tests commonly used to study acute antinociceptive activity, namely the writhing test and the capsaicin test. Our results demonstrated that NioIbu, administered 2 h before testing, reduced nociception, whereas the free form of ibuprofen was ineffective. In a model of inflammatory pain, hyperalgesia induced by zymosan, NioIbu induced a long-lasting reduction in hyperalgesia in treated mice. In a model of neuropathic pain induced by sciatic nerve chronic constriction, NioIbu reduced both neuropathy-induced allodynia and hyperalgesia. The results obtained in our experiments suggest that pH-sensitive niosomes containing Polysorbate 20 derivatized by Glycine is an effective model for NSAIDs delivery, providing durable antinociceptive effects and reducing the incidence of side effects.

Keywords: Analgesia; Ibuprofen; NSAIDs; Pain; pH-sensitive niosomes.