In this study, the encapsulation of curcumin (Cur) in “drug-in-cyclodextrin-in-liposomes (DCL)” by following the double-loading technique (DL) was proposed, giving rise to DCL–DL. The aim was to analyze the effect of cyclodextrin (CD) on the physicochemical, stability, and drug-release properties of liposomes. After selecting didodecyldimethylammonium bromide (DDAB) as the cationic lipid, DCL–DL was formulated by adding 2-hydroxypropyl-α/β/γ-CD (HPβCD)–Cur complexes into the aqueous phase. A competitive effect of cholesterol (Cho) for the CD cavity was found, so cholesteryl hemisuccinate (Chems) was used. The optimal composition of the DCL–DL bilayer was obtained by applying Taguchi methodology and regression analysis. Vesicles showed a lower drug encapsulation efficiency compared to conventional liposomes (CL) and CL containing HPβCD in the aqueous phase. However, the presence of HPβCD significantly increased vesicle deformability and Cur antioxidant activity over time. In addition, drug release profiles showed a sustained release after an initial burst effect, fitting to the Korsmeyer-Peppas kinetic model. Moreover, a direct correlation between the area under the curve (AUC) of dissolution profiles and flexibility of liposomes was obtained. It can be concluded that these “drug-in-cyclodextrin-in-deformable” liposomes in the presence of HPβCD may be a promising carrier for increasing the entrapment efficiency and stability of Cur without compromising the integrity of the liposome bilayer.

No abstract

Curcumin (Cur) is an anti-inflammatory polyphenol that can be complexed with polymeric cyclodextrin (CD) to improve solubility and bioavailability. The aim of the present work was to prepare a CurCD hydrogel to treat inflammatory skin conditions. Epichlorohydrin-β-CD (EpiβCD) was used as polymeric CD. To characterize the binary system, solid-state and in-solution studies were performed. Afterwards, an experimental design was performed to optimize the hydrogel system. Finally, the CurEpiβCD hydrogel system was tested for anti-inflammatory activity using a HaCat psoriasis cell model. Co-grinded Cur/EpiβCD binary system showed a strong interaction and Curcumin solubility was much improved. Its combination with Pluronic® F-127/hyaluronate hydrogel demonstrated an improvement in release rate and Curcumin permeation. After testing its anti-inflammatory activity, the system showed a significant reduction in IL-6 levels. Hydrogel-containing CurEpiβCD complex is a great alternative to treat topical inflammatory diseases.

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.