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

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 t1/2 (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.

Preparation, characterization and targeted delivery of serratiopeptidase immobilized on amino-functionalized magnetic nanoparticles.

Targeted delivery of serratiopeptidase enzyme immobilized on magnetic nanoparticles (MNPs) of Fe3O4 has been reported for the treatment using this enzyme. The enzyme was immobilized by covalent bonding through glutaraldehyde after amino functionalization of MNPs and parameters was studied. The enzyme bound MNPs (EMNPs) were characterized for size, crystallographic identity, phase purity, zeta potential and magnetic properties along with elemental and thermal analysis. The binding of enzyme had little effect on sizes (~10-17 nm) and on magnetic properties, but the zeta potential increased from -25 mV to +14.5 mV with surface amino groups up to 350 µmoles g(-1) MNPs, to stabilize its suspensions. In the molecular level, maximum of 17 molecules of enzyme could bind to each particle of MNPs that showed residual activity 67%, decreased KM and Vmax, good storage stability. Magnetic targeting of EMNPs increased the delivery (permeation) of drug through the membrane in in vitro study and enhanced the anti-inflammatory effect on carrageenan induced paw oedema in rats in in vivo study at much lower doses of enzyme than the doses required for treatment with free enzyme.