| The objective of this research was to develop the novel cosmetic products containing phytoestrogenic extracts loaded in nanoniosomes and to evaluate in vitro and in vivo for their anti-skin-aging properties. Among 13 herbal extracts, 8 phytoestrogenic extracts (i.e. Pueraria candollei var. mirifica, Linum usitatissimum, Glycine max, Comosa aeruginosa, Cissus quadrangularis, Tadehagi godefroyanum, Curcuma comosa, Butea superb, and P. granatum) were recommended to be selected as the potentially active ingredients for the treatment of skin aging in postmenopausal women. The phytoestrogenic model (quercetin, quercetin-3-rhamnoglucoside) could be incorporated into various types of niosomes. The permeation of phytoestrogens-loaded niosomes (particle sizes larger than 500 nm) was limited to superficial layer of the skin. The smaller in particle sizes of niosomes (100-200 nm in size) were capable to delivery that actives into the fibroblast cells. However, their toxic effects associated with induction of cell apoptosis should be concerned. The niosomes with particles in the size range of about 200 nm were most appropriate candidates as percutaneous cosmetic carriers for phytoestrogen delivery. The in vivo skin irritation test showed the niosomes tested displayed primary irritation indexes of zero, with comparable to normal saline solution. No alteration in erythema indexes could be detected for those formulations, indicating they were negligible irritants. The extracts of Aspergillus oryzae TISTR 3018-fermented G. max (FGE) and concentrated P. candollei var. mirifica (PME) were selected for subsequent experiments as phytoestrogenic extract models. The phytoestrogens-derived from these extracts could be incorporated into a wide variety of niosomal formulations. The nanoniosomes could dictate several advantages such as skin permeation, cellular uptake, release, and stability of phytoestrogenic markers. The successful in vivo studies were demonstrated that those extract loaded into the negatively and positively charged nanoniosomes could improve moisture content, total epidermal water loss, coloration, firmness, and elasticity of the skin in ovaritomized rat models. Four freeze-drying parameters to affect the redispersibility of freeze-dried niosomes were examined= variation of cryoprotectant to lipid ratio, total lipid content, cryoprotectant types, and non-ionic surfactant types. Addition of the suitable cryoprotectants to niosomes could provide ability to re-disperse into their original sizes, concentrate the niosomes, and improve stabilities of the phytoestrogens loaded nanoniosomes. A comparison of the in vitro and in vivo data showed a positive correlation for their bioavailability. Development of phytoestrogenic extracts into nanoniosomes is a promising alternative of choice to conventional cosmetic products. These results support an important role of nanoniosomes to enhance the efficacy of phytoestrogens against signs of skin aging associated with deficiency of estrogen in menopause. |