Curcumin-in-Cyclodextrins-in-Liposomes: An Alternative for Osteoarthritis Treatment

Abstract

Osteoarthritis (OA) is one of the most frequent degenerative joint diseases characterized by joint pain and stiffness traditionally treated with symptomatic drugs such as oral nonsteroidal anti-inflammatory drugs (NSAIDs )and, in extreme cases, with intra-articular corticoids. However, both these drugs are not exempt from adverse effects. Curcumin (Cur) has proven its anti-inflammatory properties and its potential as an anti-osteoarthritic drug. However, its low solubility hinders its usage and limits its therapeutic efficacy. To overcome this issue, drug-in-cyclodextrin–double-loaded liposomes (DCL–DL) were developed. These liposomes contained free drug in the lipid bilayer and drug–cyclodextrin complex in the aqueous compartment. The aim of this work was to evaluate the actual effectiveness of Cur–DCL–DL formulations in the OA treatment by intra-articular treatment. For this purpose, the monoiodoacetate (MIA) model of OA pain in rats was used. A single dose of samples containing Cur as DCL–DL, conventional liposomes (SL), and empty liposomes (EL, as control) were injected once intra-articularly. Paw pressure, beam balance, and incapacitation tests were performed to evaluate OA progression at 7 and 14 days. After ending the assay, animals were sacrificed, and histological evaluation of the ankle-joint tissue was performed. Results showed that DCL–DL significantly reduced pain and ameliorated the balance and gait of rats over the 14 days, compared to SL. Histological tests showed that DCL–DL had protective properties in some aspects of OA.

Drugs in Cyclodextrin in Liposomes: How a Suitable Formulation of an Active Substance Can Improve Its Efficiency?

“…A typical example is the intensive effort made in order to improve the bioavailability of curcumin [31][32][33][34][35][36][37]. Curcumin is a natural product extracted from the rhizomes of Curcuma longa that could be useful to treat, for instance, osteoarthritis.…”

Analysis of Nanomedicine Efficacy for Osteoarthritis

“…[ 112 ] Similarly, using curcumin as the drug, Maestrelli et al proved that the use of a cyclodextrin double‐loaded liposome, with the drug encapsulated in the lipid bilayer, reduced pain and improved gait in rats suffering from OA, and the effect of this double‐loaded liposome on improving OA was also demonstrated by histological analysis of the ankle joint. [ 113 ] In contrast to liposomes, lipid NPs are typically 100–200 nm in diameter and are capable of forming multiple micelles at the core of the particle. The main components of lipid NPs include ionizable and cationic lipids that avoid degradation of the carried cargo, cholesterol that acts as a stabilizer and helps with membrane fusion, phospholipids that serve as the structure of particles, and PEG lipids that improve the stability of the lipid NPs entering the body.…”