EtoGel for Intra-Articular Drug Delivery: A New Challenge for Joint Diseases Treatment

Ethosomes® have been proposed as potential intra-articular drug delivery devices, in order to obtain a longer residence time of the delivered drug in the knee joint. To this aim, the conventional composition and preparation method were modified. Ethosomes® were prepared by using a low ethanol concentration and carrying out a vesicle extrusion during the preparation. The modified composition did not affect the deformability of ethosomes®, a typical feature of this colloidal vesicular topical carrier. The maintenance of sufficient deformability bodes well for an effective ethosome® application in the treatment of joint pathologies because they should be able to go beyond the pores of the dense collagen II network. The investigated ethosomes® were inserted in a three-dimensional network of thermo-sensitive poloxamer gel (EtoGel) to improve the residence time in the joint. Rheological experiments evidenced that EtoGel could allow an easy intra-articular injection at room temperature and hence transform itself in gel form at body temperature into the joint. Furthermore, EtoGel seemed to be able to support the knee joint during walking and running. In vitro studies demonstrated that the amount of used ethanol did not affect the viability of human chondrocytes and nanocarriers were also able to suitably interact with cells.

Development and evaluation of a heparin gel for transdermal delivery via laser-generated micropores

Aim: Our study investigated the feasibility of transdermal delivery of heparin, an anticoagulant used against venous thromboembolism, as an alternative to intravenous administration. Materials & methods: Skin was pretreated using ablative laser (Precise Laser Epidermal System [P.L.E.A.S.E.®] technology) for enhanced delivery of heparin. In vitro permeation studies using static Franz diffusion cells provided a comparison between delivery from 0.3% w/v heparin-loaded poloxamer gel and solution across untreated and laser-treated dermatomed porcine ear skin. Results: No passive delivery of heparin was observed. Laser-assisted delivery from solution (26.07 ± 1.82 μg/cm2) was higher (p < 0.05) than delivery from heparin gel (11.28 ± 5.32 μg/cm2). However, gel is likely to sustain the delivery over prolonged periods like a maintenance dose via continuous intravenous infusion. Conclusion: Thus, ablative laser pretreatment successfully delivered heparin, establishing the feasibility of delivering hydrophilic macromolecules using the transdermal route.

Formulation and Physical Characterization of Bio-Degradable Chitosan-Poloxamer Gel Base for Local Drug Delivery

Objective: Thermo-modulated in-situ hydrogel (TSHG) are formulated routinely utilizing poloxamer for extended drug release. However physical properties of such formulations may have some flaws, which can be rectified using a combination of polymers with better physical properties such as chitosan. The purpose of the present study was to fabricate biodegradable chitosan-poloxamer-based in-situ drug delivery systems and assessment of their physical properties. Methods: The present chitosan-poloxamer gel base was formulated using a two-stage method. Initially, chitosan gel was prepared by dissolving 1% w/w chitosan in glacial acetic acid. The poloxamer gel was prepared using “cold method”. The final chitosan-poloxamer gel base was prepared by mixing equal amounts of both solutions and evaluated for physical and mechanical properties. Result and Discussion: The DSC thermogram demonstrated no obvious interactions among ingredients or micellization temperature. The gelation temperature of the gel was between 27 and 330C. The pH was 7 with slight clarity. The viscosity of the gel ranged from 15.14 to 41.19 pa.s. The gel was syringable between 4-300C and biodegradable under physiological conditions. The mean particle size of the gel under SEM was found in the range of 300-554 nm. Conclusion: After the evaluation of the formulation, it can be concluded that all the ingredients in the gel showed good compatibility with each other, which could form a stable and homogeneous gel with favorable mechanical and physical properties. Keywords: chitosan, drug delivery system, hydrogels, poloxamer

Formulation of Chitosan-Ethylenediaminetetraacetic Acid/Poloxamer Gel Containing Fruit’s Hull of Garcinia mangostana Extract

The purpose of this study was to develop the formulation of chitosan-ethylenediaminetetraacetic acid (EDTA)/poloxamer containing GM extract gel. The GM extract with a concentration of 0.5% wt was incorporated into a gel formulation. The physical appearance, pH, viscosity and percentage label amount of GM extract gel were performed. The in vitro antioxidant activity of gel were evaluated using (2,2-diphenyl-1-picrylhydrazyl (DPPH) method. The antibacterial activity against Staphylococcus aureus was evaluated by the zone of inhibition method. The mucoadhesive property was investigated using viscosity technique. The results illustrate that the chitosan-EDTA/poloxamer containing GM extract gel had a yellow colour of GM extract. The pH of a gel was in the range of 4.47 – 6.87. The percentage label amount of gel was in the range of 98.71 – 99.37% and the viscosity of gel were in the range of 14767 – 14784 mPa/s and 9607 – 9641 mPa/s. The TSol-Gel temperature was 35 oC. The antioxidant activities (IC50) which evaluated by DPPH method of all gel was in the range of 13.20 – 13.57 mg/ml. The zone of inhibition of gel against S.aureus was in the range of 8.17 – 10.52 mm. The chitosan-EDTA may improve the mucoadhesive property of gel. In conclusion, the chitosan-EDTA/poloxamer containing GM extract gel may have the potential for pharmaceutical and wound healing application.

Dexamethasone and Dexamethasone Phosphate Entry into Perilymph Compared for Middle Ear Applications in Guinea Pigs

Dexamethasone phosphate is widely used for intratympanic therapy in humans. We assessed the pharmacokinetics of dexamethasone entry into perilymph when administered as a dexamethasone phosphate solution or as a micronized dexamethasone suspension, with and without inclusion of poloxamer gel in the medium. After a 1-h application to guinea pigs, 10 independent samples of perilymph were collected from the lateral semicircular canal of each animal, allowing entry at the round window and stapes to be independently assessed. Both forms of dexamethasone entered the perilymph predominantly at the round window (73%), with a lower proportion entering at the stapes (22%). When normalized by applied concentration, dexamethasone phosphate was found to enter perilymph far more slowly than dexamethasone, in accordance with its calculated lipid solubility and polar surface area properties. Dexamethasone phosphate therefore has a problematic combination of kinetic properties when used for local therapy of the ear. It is relatively impermeable and enters perilymph only slowly from the middle ear. It is then metabolized in the ear to dexamethasone, which is more permeable through tissue boundaries and is rapidly lost from perilymph. Understanding the influence of molecular properties on the distribution of drugs in perilymph provides a new level of understanding which may help optimize drug therapies of the ear.