Nanocrystals for improved dermal drug delivery

Nanocrystals of Fusidic Acid for Dual Enhancement of Dermal Delivery and Antibacterial Activity: In Vitro, Ex Vivo and In Vivo Evaluation

“…It has been reported that particles below 1 µm preferentially accumulate in the hair follicles [58] and it is acknowledged that the smaller the particle is the deeper the localization in the hair follicles will be [59,60]. Also, FA-NC might possess, as previously reported for nanosized materials, an increased adhesiveness to biological membranes [35], thus resulting in longer retention time at the site of application leading to higher drug percutaneous absorption. From a translational point of view, FA-NC can be tuned in term of PS to either localize drugs into the skin layers to result in a local action with reduced systemic drug delivery and toxicity or can be tailored for transdermal delivery to result in high systemic drug bioavailability due to high down deeper permeation through the entire skin.…”

“…Although the application of FA-NC suspension to the skin is expected to increase the rate of penetration of FA into the skin [34]; yet, from a translational point of view, the developed FA-NC should be incorporated into a dermal product such as cream, ointment, or gel to assess its antibacterial Pharmaceutics 2020, 12, 199 7 of 27 activity. Creams were reported to be more effective vehicles for the incorporation of NC compared to other vehicles such as oleogels and hydrogels [35]. FA-NC-F12 and FA-NC-F12/L were admixed with the water phase of a cream as a vehicle to form a topical product for further studies.…”

“…Optimization results revealed that formulation "F12" is the optimized system when the optimization conditions were set to the smallest PS and the lowest SV with a composite desirability factor of 0.909. A more uniform size distribution of NC was reported to provide a higher physical stability, while a smaller PS was found to improve the passive diffusion of poorly soluble actives and promote their penetration deeper into the skin layers [35]. The selected optimum formulation (F12) was prepared using PVA 4-88 as a stabilizer, a drug to stabilizer ratio of 1:4 and a homogenization time of 10 min.…”

“…In one study, it was shown that the local concentration of dissolved drug on the site of application and not the concentration in the whole formulation is the determining factor for optimal dermal penetration of actives from NC formulations [54]. In another study, it was reported that the excipients used in the NC formulation have a tremendous influence on the dermal penetration of actives [35].…”

“…From a translational point of view, the developed FA-NC should be incorporated into a dermal product such as cream, ointment or gel to assess its antibacterial activity. Not only creams are reported to be effective vehicles for the incorporation of NC for enhanced skin permeation compared to other vehicles [35] but also vehicles and excipients are reported to greatly affect the penetration of incorporated actives into the skin [35,61]. For these reasons, a cream formulation was chosen to incorporate FA-NC to eliminate the vehicle effect when using marketed Fucidin cream as a control in the following studies.…”