Nalbuphine via nose
To manage moderate to severe pain nalbuphine, an opioid analgesic, is often prescribed. The medicine has to be injected every few hours. This can be painful. And someone has to administer the injection.
If nalbuphine could be administered nasally, both problems could be solved. When given intranasally, the drug may reach brain target sites without passing the blood brain barrier. The method might even reduce the dose required for pain relief.
A team of researchers from DRDO, Delhi and other institutes decided to load nalbuphine in solid lipid nanoparticles – a method used in preparing nasal delivery of drugs.
They used phosphatidylcholine, a lipid which is solid at room temperature to package nalbuphine as a nano formulation. Phosphatidylcholine is a normal constituent of our cell membranes and easily metabolised in the body.
To a solution of nalbuphine in ethanol, The researchers added phosphatidylcholine at higher than room temperature. To make a nanoemulsion, they added Tween 80 as a surfactant and Pluronic-127 as a co-surfactant in water and used ultrasound to make the nanoparticles. After centrifuging and drying, they had solid lipid nanoparticles ranging from about 30 to 80 nanometres.
To test whether the nanoparticles are absorbed in mucosa, they loaded the nanoparticles with rhodamine B dye and tried it on a goat mucosal membrane.
“Dye staining shows drug penetration to a depth of up to 30 micrometres”, says Nitin Sharma, Meerut Institute of Engineering and Technology.
To check the nanoparticle distribution in the body, the team introduced radiolabelled nalbuphine nanoparticles into the noses of mice.
“The drug showed up in the brain within ten minutes and was distributed in the system within 30 minutes”, says Sakshum Khanna, Pandit Deen Dayal Petroleum Universtity, Gujarat.
“Nalbuphine nanoparticles remained in the brain for 8 hours. This suggests that its effect lasts long”, says Harvinder Popli, Delhi Pharmaceutical Sciences and Research University.
To compare the analgesic effect of the nanoparticles and injections, the team tested mice with induced pain. The intranasal analgesic worked better than injections.
“Our experiment on mice brain cells suggests no cytotoxicity”, says Gaurav Kumar Jain, Delhi Pharmaceutical Sciences and Research University.
“We also checked the nanoparticle’s cytotoxicity on human embryonic kidney cells. Up to 750 micromolar was safe”, says Nazia Khan, Jamia Hamdard University, Delhi.
“Intranasal nalbuphine administration is easy and cost-effective. The dose is lower. So are side effects”, says Dhruv Kumar Nishad, DRDO.
“Of course, further research is required before patients with pain can use nalbuphine intranasally”, Aseem Bhatnagar, DRDO.
Chem. Phys. Lipids, 236: 105060 (2021);
Dhempe College of Arts and Science, Goa University
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