Solid-in-oil nanodispersions for transdermal drug delivery systems

Abstract

Transdermal administration of drugs has advantages over conventional oral administration or administration using injection equipment. The route of administration reduces the opportunity for drug evacuation before systemic circulation, and enables long-lasting drug administration at a modest body concentration. In addition, the skin is an attractive route for vaccination, because there are many immune cells in the skin. Recently, solid-in-oil nanodisperison (S/O) technique has demonstrated to deliver cosmetic and pharmaceutical bioactives efficiently through the skin. S/O nanodispersions are nanosized drug carriers designed to overcome the skin barrier. This review discusses the rationale for preparation of efficient and stable S/O nanodispersions, as well as application examples in cosmetic and pharmaceutical materials including vaccines. Drug administration using a patch is user-friendly, and may improve patient compliance. The technique is a potent transcutaneous immunization method without needles.

Keywords: Nanocarrier; Solid-in-oil nanodispersion; Transcutaneous immunotherapy; Transdermal drug delivery; Vaccine.

Figure 1

Preparation and application methods (A) and physical appearances and size distribution curves (B) of S/O dispersions. W/O emulsions prepared by ultrasound, rotor‐stator or high pressure homogenization are subjected to lyophilization, and then the surfactant/drug complex is redispersed in oilvehicles to form S/O nanodispersions. The nanodispersions are applied to the intact skin using patches. Sucrose laurate (L‐195), sucrose palmitate (P‐170), sucrose stearate with HLB 1 and 2 (S‐170 and S‐270, respectively), sucrose oleate (O‐170), and sucrose erucate (ER‐290) were examined to prepare S/O nanodispersions containing OVA, and L‐195, O‐170 and ER‐290 formed stable nanosized dispersions, while naked OVA was insoluble in IPM. Particle size distribution was measured by dynamic light scattering using Zetasizer NanoZS (Malvern). Reproduced with permission 66. Coypright 2014, Royal Society of Chemistry.

Figure 2

Fluorescence microscopic images of Yucatan micropig skin sections (A), and mouse ear epidermal sheet (B), adapted with permission 66. Coypright 2014, Royal Society of Chemistry and adapted with permission 70. Coypright 2008, Elsevier, respectively. The Yucatan micropig skin was treated with S/O nanodispersions composed of fluorescein isothiocyanate (FITC)‐labeled insulin and rhodamine‐labeled 1,2‐dioleoyl‐sn‐glycero‐3‐phosphoethanolamine (rhodamine‐) for 48 h, and sectioned for observation by fluorescence microscopy. Another S/O nanodispersion consisting of FITC‐labeled OVA and rhodamine‐DOPE was applied to mouse ear for 24 h, and then the epidermal sheet was isolated from the ear and observed by confocal laser scanning fluorescence microscopy. Rhodamine‐DOPE mostly remained in the stratum corneum, whereas, FITC‐protein permeated the viable epidermis and dermis. The lipid and proteins penetrated the intercellular pathways.

Figure 3

Concept of transcutaneous immunotherapy using S/O nanodispersions. Antigens are released in the stratum corneum and permeate the epidermis and dermis. LCs and dDCs capture antigen and migrate to lymphatic vessels and skin‐draining lymph nodes. They present antigens to nearby CD4+ and CD8+ T cells, or pass them to other DCs. LCs may activate T regulatory cells under steady‐state conditions by the existence of antigen, thereby inducing alleviation of allergic responses. Dendritic epidermal γδ T cells may promote Th2 cell induction, and dermal γδ T cells may induce CD4+ T cells under inflammatory conditions.

Figure 4

Time schedule of immunization and tumor cell inoculation (A), and antitumor effect of OVA administered by topical patch or s.c. injection (B). OVA in the S/O nanodispersion system induced antigen‐specific cancer immunity comparable to that in a PBS solution administered by s.c. injection. Adapted with permission 131. Coypright 2015, Royal Society of Chemistry.