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Indian scientists develop novel drug delivery method to cut side effects of arthritis drug

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New Delhi, October 26: Indian scientists have given a new lease of life to the arthritis medicine sulfapyridine by employing an innovative drug delivery method to remove its side effects.

Indian scientists develop novel drug delivery method to cut side effects of arthritis drug

Sulfapyridine is the third oldest drug still in use in the treatment of rheumatoid arthritis, an autoimmune inflammatory joint disease, according to the researchers from Lovely Professional University (LPU) in Punjab.

However, long term use of the drug results in side effects such as nausea or vomiting, rashes, dizziness, anxiety and abdominal pain, they said.

"As the molecule has side effect due to its higher dose, we developed a formulation which can be delivered directly to the site of action and thus is safe," said Bhupinder Kapoor, Associate Professor, School of Pharmaceutical Sciences, LPU, told PTI.

In their study published in the peer-reviewed journal 'Materials Science and Engineering C’, the researchers reported developing a prodrug of sulfapyridine and then incorporated it into an innovative delivery system.

The prodrug exhibited better retention in liposomes, as compared to the drug, thus reducing the symptoms of inflammation. Liposomes are spherical vesicles having at least one lipid bilayer which are used as a vehicle for administration of pharmaceutical drugs.

The prodrug treatment is administered by injecting the affected area of the patient, and not through oral consumption, according to the researchers. This means that the medication only remains in the affected area, without spreading to the rest of the body, they said.

The research team, including Kapoor, Monica Gulati and Sachin K. Singh from LPU, successfully conducted the pre-clinical trials as well as the testing of the drug delivery mechanism. "We conducted a study to understand the efficacy of sulfapyridine-derived liposomes.

In arthritic rats, prodrug liposomes were found to reverse the symptoms of inflammation, including the levels of biochemical markers," Kapoor explained. "Therefore, liposomes of bio-responsive prodrugs offer a revolutionary approach in the treatment of rheumatoid arthritis," he said.

The study was carried in collaboration with researchers at Fortis Hospital, Ludhiana & JSS College of Pharmacy, Ooty, Tamil Nadu. Calling the results of the study as "promising", Dr. Arup Kumar Banerjee from North Bengal Medical College and Hospital in Siliguri, West Bengal noted that prodrugs are compounds, or a derivative of a drug, that themselves are pharmacologically inactive but after administration get metabolised in the body into its active form.

"Prodrug form increases the bioavailability of the actual drug by defying metabolism in site other than the intended one and also decreases the adverse side effect by selective absorption or metabolism at the target cells or organs," Banerjee, who was not involved in the study, told PTI. Around 10 per cent of all drugs being used today are administered in the body in prodrug form, he added.

At present sulfapyridine is used in the form of sulfasalazine which is recommended orally in high dose and has few side effects due to exposure to nontarget sites, the researchers said. For the successful retention of the drug at the injection site, they synthesised its lipophilic prodrug which is retained in the injection site for a longer time period and required in very low dose, therefore has no side effects and dosing frequency is also very less.

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As sulfapyridine is not a suitable molecule due to poor solubility, the researchers synthesised its prodrug which can be retained in injection site for a longer time period, and therefore is effective in very low dose and without any side effect.

The researchers said their prodrug will need approval for sales and marketing from India's drug regulatory body. The team has filed for a patent, and the pre-evaluation phase is now complete. They are also applying for an international patent for this new drug delivery method.

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