Sublingual delivery of chondroitin sulfate conjugated tapentadol loaded nanovesicles for the treatment of osteoarthritis

Abstract

Recent treatment approaches of osteoarthritis (OA) face a number of obstacles due to the progressive multitude of pain generators, nociceptive mechanisms, first pass mechanism, less efficacy and compromised safety. The present study was aimed to bring a novel approach for the effective management of OA, by developing sublingual targeted nanovesicles (NVs) bearing tapentadol HCl (TAP), surface modified with chondroitin sulfate (CS). Optimized nontargeted nanovesicle formulation (MB-NV) was developed by an ultrasound method, characterized as spherical in shape, nanometric in size (around 150 nm) with narrow size distribution (polydispersity index <0.5), and good entrapment efficiency (around 50%). MB-NV conjugated with CS which was confirmed by IR and ¹H NMR spectroscopy. C-MB-NV showed improved pharmacokinetics parameters i.e. increased t_1/2 (9.7 h), AUC (159.725 μg/mL*h), and MRT (14.99 h) of TAP than nontargeted formulation and plain drug soln. C-MB-NV in in vitro release studies proved sustained drug release pattern for more than 24 h following Higuchi model kinetics with Fickian diffusion (n ≤ 0.5).Targeted nanovesicles exhibited an improved bioavailability and enhanced analgesic activity in a disease-induced Wistar rat model which indicated the superior targeting potential of C-MB-NV exploiting CD44 receptors as mediators, overexpressed at the affected joints in the OA model. It could be a propitious approach to accustomed therapies for methodical and efficient management in advanced OA therapy.

Keywords:

• Osteoarthritis
• chondroitin sulfate
• nanovesicles
• opioids
• sublingual delivery
• tapentadol
• analgesics

Acknowledgements

We are thankful to Innova Captab, Baddi (H.P.) for providing TAP as a gift sample. The authors also thank AIIMS, New Delhi, for carrying out TEM studies and Jamia Hamdard, New Delhi, for providing the facility of ¹H NMR spectroscopy.

Disclosure statement

The authors declare no competing financial interest, direct or indirect, in the subject matter or materials discussed in the manuscript.