Injectable Liposomal Formulations of Opiorphin As a New Therapeutic Strategy in Pain Management

Abstract

Background: Conventional and PEGylated liposomes were developed, aimed at improving the pain-killing effect of opiorphin. Methods: The antinociceptive action of the formulations was investigated on rats (tail-flick test), and compared with that of opiorphin and morphine aqueous solutions (all at 5 mg/kg). Results: Opiorphin loading in conventional liposomes enabled a 28% AUC increase with respect to free peptide. PEGylated liposomes provided AUC values 80, 60 and 40% higher than free peptide, morphine and opiorphin-loaded conventional liposomes, respectively. Moreover, opiorphin entrapment in PEGylated liposomes increased analgesic effect duration by more than 50%. These results were attributed to the greater effectiveness of PEGylated liposomes in protecting the drug and prolonging its circulation time. Conclusion: Opiorphin-loaded PEGylated-liposomes can represent a valid alternative to morphine in pain management.

Opiorphin is an endogenous peptide with a strong analgesic effect, superior to that of morphine and without the several side effects of morphine and morphine-like drugs. Conventional and PEGylated liposomes were developed, aimed at protecting the drug from rapid metabolization and improving its therapeutic efficacy. In vivo rat experiments proved that PEGylated liposomes were more effective than conventional liposomes, significantly enhancing intensity and duration of the pain-killing effect. Opiorphin-PEGylated liposomes showed a more intense and prolonged pain-killing effect than morphine at the same dosage. Therefore, this new formulation could represent a noticeable improvement in pain management therapy, as a valid morphine alternative.

Keywords::

• conventional liposomes
• improved antinociception
• opiorphin
• PEGylated liposomes
• tail-flick latency test

Financial & competing interests disclosure

This work was supported by MIUR (Italian Ministry of University and Research). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript, apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct

The authors state that animal experiments were carried out in agreement with both the principles and procedures approved by the local ethics committee and the US Public Health Service's Policy on Human Care and Use of Laboratory animals. The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations.

Additional information

Funding

This work was supported by MIUR (Italian Ministry of University and Research). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript, apart from those disclosed.