Increased localized delivery of piroxicam by cationic nanoparticles after intra-articular injection

Abstract

Piroxicam (PRX), a potent nonsteroidal anti-inflammatory drug, is prescribed to relieve postoperative and/or chronic joint pain. However, its oral administration often results in serious gastrointestinal adverse effects including duodenal ulceration. Thus, a novel cationic nanoparticle (NP) was explored to minimize the systemic exposure and increase the retention time of PRX in the joint after intra-articular (IA) injection, by forming micrometer-sized electrostatic clusters with endogenous hyaluronic acid (HA) in the synovial cavity. PRX-loaded NPs consisting of poly(lactic-co-glycolic acid), Eudragit RL, and polyvinyl alcohol were constructed with the following characteristics: particle size of 220 nm, zeta potential of 11.5 mV in phosphate-buffered saline, and loading amount of 4.0% (w/w) of PRX. In optical and hyperspectral observations, the cationic NPs formed more than 50 μm-sized aggregates with HA, which was larger than the intercellular gaps between synoviocytes. In an in vivo pharmacokinetic study in rats, area under the plasma concentration–time curve (AUC0–24 h) and maximum plasma concentration (Cmax) of PRX after IA injection of the cationic NPs were <70% (P<0.05) and 60% (P<0.05), respectively, compared to those obtained from drug solution. Moreover, the drug concentration in joint tissue 24 h after dosing with the cationic NPs was 3.2-fold (P<0.05) and 1.8-fold (P<0.05) higher than that from drug solution and neutrally charged NPs, respectively. Therefore, we recommend the IA cationic NP therapy as an effective alternative to traditional oral therapy with PRX, as it increases drug retention selectively in the joint.

Intra-articular injection of kartogenin-conjugated polyurethane nanoparticles attenuates the progression of osteoarthritis

“…Positively charged drug-carriers showed faster penetration and higher uptake than their neutral same-sized counterpart (Bajpayee et al., 2014 ). It is also reported that cationic polymeric nanoparticles had increased retention time and prolonged release profile in joints after IA injection, by forming electrostatic clusters with endogenous hyaluronic acid (Morgen et al., 2013 ; Kim et al., 2016 ). As previously reported, pendant amino groups (–NH 2 ) could increase the cationic nature of polyurethane (Fang et al., 2014 ), we speculated that the amino groups could promote electrostatic interactions with anionic proteoglycans and provide longer retention in cartilage matrix.…”

Poly(ester amide) particles for controlled delivery of celecoxib

“…Several different classes of drug delivery systems have been studied for intra‐articular use including hydrogels, nanoparticles, and crystalline drug formations . Although each of these systems has different structures and properties, they are all designed to release the drug over prolonged periods after injection into the joint without adverse reactions of the joint tissue to the delivery platform.…”

“…5,6 The intra-articular injection of the drug using a delivery system can potentially lead to a higher delivered dose while minimizing the side effects to off-target tissues by reducing systemic drug levels. 7 Several different classes of drug delivery systems have been studied for intra-articular use including hydrogels, 8 nanoparticles, 9,10 and crystalline drug formations. 11 Although each of these systems has different structures and properties, they are all designed to release the drug over prolonged periods after injection into the joint without adverse reactions of the joint tissue to the delivery platform.…”

Polymeric Nanoparticles for Increasing Oral Bioavailability of Curcumin

“…This non-biodegradable, water insoluble and positively-charged polymer is often used to prepare sustained-release formulations adapted to oral routes. Nanotechnology takes has taken advantage of ERL’s bioadhesive properties in the proposed drug delivery systems for oral [ 22 , 23 ], ocular [ 24 ] and intraarticular [ 25 ] administration. Owing to the above-mentioned properties, ERL is a promising material for preparing nanocarriers for oral delivery of curcumin.…”