Penetration enhancer-containing vesicles for cutaneous drug delivery

The function of vesicles as topical delivery systems is controversial with variable effects being reported in relation to the type of vesicles and their composition. A wide variety of lipids and surfactants can be used to prepare vesicles, and vesicle composition and preparation method influence their physicochemical properties (size, charge, lamellarity, thermodynamic state, deformability) and, therefore, their efficacy as drug delivery systems. In this chapter, composition, preparation, and results obtained by using penetration enhancer-containing vesicles, liposomes prepared by associating different penetration enhancers to phospholipids, are described. These systems have shown to improve cutaneous drug delivery, thanks to a combination of properties of vesicle carriers and penetration enhancers

Structural studies of lipid based nanosystems for drug delivery: X-Ray Diffraction (XRD) and Cryogenic Transmission Electron Microscopy (cryo-TEM)

Lipid based nanosystems have potential use as matrixes able to dissolve and deliver active molecules in a controlled fashion, thereby improving their bioavailability and reducing side-effects. In particular nanoparticles based on lipids have been widely proposed as novel drug carrier systems. For instance solid lipid nanoparticles (SLN) join the advantages of colloidal lipid emulsions with those of solid matrix particles. The second generation of SLN is represented by nanostructured lipid carriers (NLC), which are composed of a solid lipid matrix with a certain content of a liquid lipid phase. Another type of lipid dispersion that can provide matrixes for the sustained release of drugs is represented by monooleine aqueous dispersions (MAD). MAD are heterogeneous systems generated by the dispersion of an amphiphilic lipid, such as monoolein, in water. They are constituted of complex lyotropic liquid crystalline nanostructures like micellar, lamellar, hexagonal, and cubic phases. In order to characterize nanosystems it is important to carry out detailed systematic investigations. X-ray diffraction and microscopy give informations about shape, inner structure and dimensions of powders and dispersions that could not otherwise be identified. This chapter provides an overview about the use of x-ray diffraction and cryogenic transmission electron microscopy as techniques for characterizing lipid nanosystems recently developed by our research group

Hydroxyzine from topical phospholipid liposomal formulations: Evaluation of peripheral antihistaminic activity and systemic absorption in a rabbit model

Hydroxyzine, an effective but sedating H1-antihistamine is given orally to treat allergic skin disorders. This study was performed to assess the peripheral H1-antihistaminic activity and extent of systemic absorption of hydroxyzine from liposomes applied to the skin. Using L-α-phosphatidylcholine (PC), small unilamellar vesicles (SUVs) and multilamellar vesicles (MLVs) containing hydroxyzine were prepared. Hydroxyzine in Glaxal Base (GB) was used as the control. Using a randomized, crossover design, each formulation, containing 10 mg of hydroxyzine, was applied to the shaved backs of 6 rabbits (3.08±0.05 kg). Histamine-induced wheal tests and blood sampling were performed at designated time intervals up to 24 hours. Compared with baseline, hydroxyzine from all formulations significantly suppressed histamine-induced wheal formation by 75% to 95% for up to 24 hours. Mean maximum suppression, 85% to 94%, occurred from 2 to 6 hours, with no differences among the formulations. The areas of plasma hydroxyzine concentration versus time area under the curve (AUCs) from PC-SUV and PC-MLV, 80.1±20.8 and 78.4±33.9 ng/mL/h, respectively, were lower than that from GB, 492±141 ng/mL/h (P<.05) over 24 hours. Plasma concentrations of cetirizine arising in-vivo as the active metabolite of hydroxyzine, from PC-SUV, PC-MLV, and GB, were similar with AUCs of 765±50, 1035±202, and 957±227 ng/mL/h, respectively (P<.05). Only 0.02% to 0.06% of the initial hydroxyzine dose remained on the skin after 24 hours. In this model, hydroxyzine from SUV and MLV had excellent topical H1-antihistaminic activity, and minimal systemic exposure occurred. Cetirizine formed in-vivo contributed to some of H1-antihistaminic activity

Drug-Cyclodextrin-Vesicles Dual Carrier Approach for Skin Targeting of Anti-acne Agent

In the present study attempt was made for preparation of isotretinoin-hydroxypropyl β cyclodextrin (HP-β-CD) inclusion complex and encapsulate this complex in elastic liposomes to study the effect of dual carrier approach on skin targeting of isotretinoin. The isotretinoin HP-β-CD complex was prepared by freeze-drying method and characterized by IR spectroscopy. The drug and drug-CD complex loaded elastic liposomal formulation were prepared and characterized in vitro, ex-vivo and in vivo for shape, size, entrapment efficiency, no. of vesicles per cubic mm, in vitro skin permeation and deposition study, photodegradation and skin toxicity assay. The transdermal flux for different vesicular formulations was observed between 10.5 ± 0.5 to 13.9 ± 1.6 μg/cm2/h. This is about 15-21 folds higher than that obtained from drug solution (0.7 ± 0.1 μg/cm2/h) and 4-5 folds higher than obtained with drug-CD complex solution (2.7 ± 0.1 μg/cm2/h). The amount of drug deposit was found to increase significantly (p < 0.05) by cyclodextrin complexation (30.1 ± 0.1 μg). The encapsulation of this complex in elastic liposomal formulation further increases its skin deposition (262.2 ± 21 μg). The results of skin irritation study using Draize test also showed the significant reduction in skin irritation potential of isotretinoin elastic liposomal formulation in comparison to free drug. The results of the present study demonstrated that isotretinoin elastic liposomal formulation possesses great potential for skin targeting, prolonging drug release, reduction of photodegradation, reducing skin irritation and improving topical delivery of isotretinoin