The systemic use of non-steroidal anti-inflammatory drugs (NSAIDs) which act by inhibiting cyclooxygenase (COX) is severely hampered by gastric and peptic ulcers. The topical delivery of NSAIDs has the advantages of avoiding gastric and peptic ulcers and delivering the drug to the inflammation site. Importance of aceclofenac as a new generational NSAID has inspired the development of topical dosage forms. This mode of administration may help to avoid typical side effects of NSAIDs associated with oral and systemic administration such as gastric irritation, particularly diarrhoea, nausea, abdominal pain and flatulence. The aim of this study was to formulate topical gel containing 1% of aceclofenac in carbopol and PEG base and to evaluate it for analgesic and antiinflammatory activity using carrageenan-induced thermal hyperalgesia and paw oedema in rats. Carrageenan administration into the hind paw produced a significant inflammation associated with hyperalgesia as shown by decreased rat paw withdrawal latency in response to a thermal stimulus (47+/-0.5 degrees C) 4 h after carrageenan injection. Topical application of AF1 significantly attenuated the development of hypersensitivity to thermal stimulus as compared to control (P<0.05) and other formulation treated groups (P<0.05). All the AF semisolid formulations, when applied topically 2 h before carrageenan administration, inhibited paw edema in a timedependent manner with maximum percent edema inhibition of 80.33+/-2.52 achieved with AF1 after 5 h of carrageenan administration However, topical application of AF2 markedly prevented the development of edema as compared to other formulation (AF2 and AF3) treated groups (P<0.05). Among all the semisolid formulations, Carbopol gel base was found to be most suitable dermatological base for aceclofenac.
Arthritic disease is one of the most common diseases in adults and a leading cause of joint degeneration. Dexibuprofen (DEX) is routinely used for the treatment of rheumatoid arthritis, acute postoperative pain, primary dysmenorrheal, and in lower back pain. However, it is poorly water soluble with compromised bioavailability, and hence has limited therapeutic activity. In order to overcome these issues, we studied the formulation and characterization of nanoemulsion based system i.e nanoemulgel of DEX. This study aimed to prepare topical nanoemulgel containing 2 % DEX and solubility-enhanced DEX via ternary inclusion complexation (DEX-SE-T) and to compare it with commercially available 5 % Ibuprofen gel as there is no topical formulation of DEX is available in the market currently. A pseudoternary phase diagram was constructed using the spontaneous water titration method. Blank and drug-loaded nanoemulgel were prepared using a high-speed homogenization method. All the formulations were evaluated in terms of particle size, pH, conductivity, viscosity, zeta potential, and ex vivo drug permeation. DEX loaded nanoemulgel yield enhanced in vitro skin permeation than the commercially available 5 % ibuprofen gel. The optimized nanoemulgel formulation (DEX-SE-T) was tested in in vivo anti-inflammatory models including cotton pellets-induced abdominal granuloma (chronic inflammation) and carrageenan-induced paw edema (acute inflammation). DEX-SE-T loaded nanoemulgel has improved in vivo anti-inflammatory activity as compared to ibuprofen gel. DEX-SE-T could be a promising option for effective topical treatment of inflammatory conditions.
The present study was conducted with the aim to investigate the immuno-modulatory and histological stabilization effects of nanocarrier-based transcutaneous co-delivery of hydrocortisone (HC) and hydroxytyrosol (HT). In this investigation, the clinical and pharmacological efficacies of nanoparticle (NP)-based formulation to alleviate 2,4-dinitrofluorobenzene (DNFB)-induced atopic dermatitis (AD) was explored by using an NC/Nga mouse model. Ex vivo visual examination of AD induction in experimental mice indicated remarkable control of NP-based formulations in reducing pathological severity of AD-like skin lesions. Therapeutic effectiveness of NP-based formulations was also evaluated by comparing skin thickness of AD-induced NP-treated mice (456±27 µm) with that of atopic mice (916±37 µm). Analysis of the immuno-spectrum of AD also revealed the dominance of NP-based formulations in restraining immunoglobulin-E (IgE), histamine, prostaglandin-E2 (PGE2), vascular endothelial growth factor-α (VEGF-α), and T-helper cells (TH1/TH2) producing cytokines in serum and skin biopsies of tested mice. These anti-AD data were further supported by histological findings that revealed alleviated pathological features, including collagen fiber deposition, fibroblasts infiltration, and fragmentation of elastic fibers in experimental mice. Thus, NP-mediated transcutaneous co-delivery of HC and HT can be considered as a promising therapy for managing immunological and histological spectra associated with AD.