In Vitro Skin Penetration of Dendrimer Nanoparticles

Abstract

Introduction: Dendrimers are highly branched, stable polymeric nanoparticles with functional groups capable of binding other molecules and may increase delivery of chemicals into skin. Materials and Methods: We examined the skin penetration of generation 3 (G3) to generation 6 (G6) polyamidoamine (PAMAM) amine-terminated (positively charged) dendrimer nanoparticles conjugated with a fluorophore (Alexa Fluor 568) for confocal imaging. The PAMAM dendrimers were further conjugated with succinic anhydride (negative surface charge) or glycidol to impart no charge (neutral). Dendrimers were applied (0.2% concentration) in aqueous solutions or cosmetic formulation onto viable pig or human cadaver skin assembled in diffusion cells. Results: After a 24-hour exposure, most fluorescence appeared in the stratum corneum (SC) or in hair follicles of both pig and human skin. We then examined the skin penetration of radiolabeled generation 4 (G4) dendrimer (0.2% concentration), conjugated with glycidol (OH) and G4 dendrimer bound to glycolic acid (GA), to determine if enhanced skin penetration of GA could occur. The skin penetration of a radiolabeled GA solution and a GA G4-OH dendrimer solution mixture was also evaluated. Most of the radioactive G4-OH dendrimer penetrating human skin remained in the SC (4.7%), with less than 1% absorbing into the epidermis and dermis. When the radiolabeled G4 dendrimer was bound to GA, penetration into SC increased significantly to 29%, and to 4% in the epidermis and dermis compared with the radiolabeled GA treatment alone (4.6%) and the radiolabeled GA G4-OH dendrimer mixture (3.4%). Using radioactivity as a marker, when labeled G4 dendrimer was bound to GA and applied to skin, there was an increase in total skin levels and total penetration levels when compared with GA and GA-dendrimer mixture. Discussion and Conclusion: It appears that the G4 dendrimer may increase the penetration of GA, demonstrating that dendrimer terminal group functionality and charge may alter skin absorption of associated chemicals.

Nanocarriers for Skin Applications: Where Do We Stand?

“…In as imilar study,K raeling et al investigated and compared the skin penetration of PA MAM dendrimers (G3 to G6, MW (g mol À1 ) % 8000-66 000) conjugated with amine moieties (positively charged), succinic anhydride (negative surface charge), and glycidol (neutral) in cosmetic formulations on viable pig or human cadaver skin using diffusion cells. [33] Confocal laser scanning micrographs showed greater penetration of G3-NH 2 dendrimer into the dermal layers of human skin compared to greater penetration of G4-OH dendrimer into the dermis of pig skin. Thei ncreased penetration of cationic dendrimers could be explained based on their interaction with negatively charged biological membranes,r esulting in an increase in permeability.…”

“…Thei ncreased penetration of cationic dendrimers could be explained based on their interaction with negatively charged biological membranes,r esulting in an increase in permeability. [33] Another efficient pathway for the penetration of particles through the skin layers is the hair follicle route as explored by Sahle et al [13] Thes tudy revealed that thermoresponsive nanogels (tNGs) with ap hase transition temperature of 32-37 8 8Cand particle sizes between 300-500 nm penetrated more effectively than smaller NGs into the hair follicle,w ith penetration depths proportional to the particle size. [13] The follicular penetration of the NPs can be explained by the "ratchet effect", defined as directed particle motion generated by anon-equilibrium perturbation of aperiodic system.…”

Recent advances and development in epidermal and dermal drug deposition enhancement technology

“…In nanocapsules, the drug is entrapped in the core whereas in nanoparticle, drug is dispersed in polymeric matrix, abdorbed, complexed, or conjugated on the surface of the particle. 80 They enhance epidermal drug deposition via a variety of mechanisms. 79 and it is still a topic of discussion.…”

“…Furthermore, dendrimers are mainly localized to the epidermal layers and hair follicles. 80 They enhance epidermal drug deposition via a variety of mechanisms.…”

The transdermal penetration of novel amphiphilic MTC-Y carrier

“…Numerous skin penetration enhancers are proposed to improve topically applied drug delivery. Hybrid terpene-amino acid enhancers, esters of terpene alcohols, niosomesdendrimer nanoparticles, peptides [8][9][10][11][12][13][14] .The another method for increased/decreased skin permeability is the use of mechanical factors such as electric devices or ultrasound, iontophoresis, sonophoresis 6,15,16 .…”