Preclinical investigation of hydroxychloroquine loaded ethosomal gel for topical treatment of rheumatoid arthritis.

PURPOSE: Hydroxychloroquine (HCQ) has been used conventionally for the management of RA. However, due to its high dose and adverse effects associated with the long-term use, its therapeutic utility is often limited. This research was undertaken to develop an ethosomes based topical dosage form of HCQ, to improve the transdermal delivery of HCQ in patients with RA.

METHODS

Ethosomes were developed by varying the concentration of ethanol, phospholipids and surfactants in the formulations. The developed ethosomal formulation was characterized for particle size, zeta potential, PDI, % entrapment efficiency, etc. Ethosomes were then incorporated into Carbopol gel and evaluated for in vitro drug release, ex vivo skin permeation and in vivo anti-inflammatory/anti-arthritic activity.

RESULTS

The ethosomes were nanometric in size (~ 210 nm), with a narrow particle size distribution (PDI =  ~ 0.25), zeta potential of around -30 mV, and high entrapment efficiency (~ 80%). The formulation exhibited controlled release of HCQ over time (~ 77% in 24 h) and improved permeation through the skin (~ 70% in 24 h) compared to conventional gel formulation. The in vivo studies demonstrated a significant decrease in the inflammatory symptoms of RA (~ 19% paw swelling inhibition compared to 22% for marketed gel) and the HCQ-loaded ethosomal gel was well tolerated by the skin with no signs of irritation. The stability studies indicated very slight drug loss (< 2%) at the end of 3 months, demonstration excellent stability of the formulation).

CONCLUSION

The ethosomes based gel formulation of HCQ has a potential to serve as an alternative to the conventional oral dosage form of the drug for the better management of RA.