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Solid nanoemulsion as antigen and immunopotentiator carrier for transcutaneous immunization
- Source :
- Cellular Immunology. 308:35-43
- Publication Year :
- 2016
- Publisher :
- Elsevier BV, 2016.
-
Abstract
- Imiquimod, a toll-like receptor 7 (TLR7) agonist, is an active pharmaceutical ingredient (API) established for the topical treatment of several dermal cancerous and precancerous skin lesions. Within this work, the immunostimulatory effect of imiquimod is further exploited in a transcutaneous immunization (TCI) approach based on a solid nanoemulsion (SN) formulation. SN contains a combination of imiquimod with the model peptide antigen SIINFEKL as a novel approach to omit needle and syringe and optimize dermal antigen administration. Excipients including sucrose fatty acid esters and the pharmaceutically acceptable oils MCT (middle chain triglycerides), avocado oil, jojoba wax and squalene are high pressure homogenized together with the antigen SIINFEKL. Freeze drying was performed to eliminate water and to achieve spreadable properties of the formulation for dermal administration. The influence of the different oil components was assessed regarding in vitro drug permeation in a Franz diffusion cell model using a murine skin setup. In vivo performance in terms of cytotoxic T-cell response was assessed in a C57BL/6 mouse model. Whereas Aldara® cream contains imiquimod in a dissolved state, the SN formulations carry the active in a suspended state. This resulted in a reduction of imiquimod permeation across murine skin from the SN when compared to Aldara® cream. In spite of this permeation rate reduction, each SN induced an in vivo immune response by specific T-cell lysis. A stabilized solid nanosuspension containing squalene/tocopherol exhibited a significantly higher performance (p⩽0.05) in comparison with Aldara® cream. MCT based SN exerted an in vivo effect comparable to Aldara®. In conclusion, anhydrous highly dispersed vehicles containing imiquimod in a submicron particle size distribution can represent promising formulations for TCI. The choice of the oil component has a strong influence on SN performance, independent of in vitro drug permeation.
- Subjects :
- 0301 basic medicine
Skin Neoplasms
Chemistry, Pharmaceutical
Immunology
Antineoplastic Agents
Imiquimod
Immunopotentiator
Biology
Administration, Cutaneous
030226 pharmacology & pharmacy
Mice
03 medical and health sciences
Freeze-drying
Squalene
chemistry.chemical_compound
Drug Delivery Systems
0302 clinical medicine
Adjuvants, Immunologic
Antigen
In vivo
medicine
Animals
Humans
Active ingredient
Chromatography
Vaccination
Permeation
Nanostructures
Mice, Inbred C57BL
030104 developmental biology
chemistry
Langerhans Cells
Aminoquinolines
Immunization
Oils
Precancerous Conditions
medicine.drug
Subjects
Details
- ISSN :
- 00088749
- Volume :
- 308
- Database :
- OpenAIRE
- Journal :
- Cellular Immunology
- Accession number :
- edsair.doi.dedup.....7fe5f7281a80c392be05dda12cb5c700