title: Non-invasive Oil-Based Method to Increase Topical Delivery of Nucleic Acids to Skin.
abstract: Topical delivery of nucleic acids to skin has huge prospects in developing therapeutic interventions for cutaneous disorders. In spite of initial success, clinical translation is vastly impeded by the constraints of bioavailability as well as stability in metabolically active environment of skin. Various physical and chemical methods used to overcome these limitations involve invasive procedures or compounds that compromise skin integrity. Hence, there is an increasing demand for developing safe skin penetration enhancers for efficient nucleic acid delivery to skin. Here, we demonstrate that pretreatment of skin with silicone oil can increase the transfection efficiency of non-covalently associated peptide-plasmid DNA nanocomplexes in skin ex vivo and in vivo. The method does not compromise skin integrity, as indicated by microscopic evaluation of cellular differentiation, tissue architecture, enzyme activity assessment, dye penetration tests using Franz assay, and cytotoxicity and immunogenicity analyses. Stability of nanocomplexes is not hampered on pretreatment, thereby avoiding nuclease-mediated degradation. The mechanistic insights through Fourier transform infrared (FTIR) spectroscopy reveal some alterations in the skin hydration status owing to possible occlusion effects of the enhancer. Overall, we describe a topical, non-invasive, efficient, and safe method that can be used to increase the penetration and delivery of plasmid DNA to skin for possible therapeutic applications.
authors.affiliation: CSIR-Institute of Genomics and Integrative Biology, South Campus, Mathura Road, New Delhi 110020, India; Academy of Scientific and Innovative Research (AcSIR), Anusandhan Bhawan, 2 Rafi Marg, New Delhi 110001, India.
authors.forename: Manika
authors.initials: M
authors.lastname: Vij
authors.affiliation: CSIR-Indian Institute of Toxicology Research, Post Box 80, Mahatma Gandhi Marg, Lucknow (Uttar Pradesh) 226001, India.
authors.forename: Shamshad
authors.initials: S
authors.lastname: Alam
authors.affiliation: Delhi Technological University, Shahbad Daulatpur, Main Bawana Road, New Delhi 110042, India.
authors.forename: Nidhi
authors.initials: N
authors.lastname: Gupta
authors.affiliation: CSIR-Institute of Genomics and Integrative Biology, South Campus, Mathura Road, New Delhi 110020, India; Academy of Scientific and Innovative Research (AcSIR), Anusandhan Bhawan, 2 Rafi Marg, New Delhi 110001, India.
authors.forename: Vishvabandhu
authors.initials: V
authors.lastname: Gotherwal
authors.affiliation: CSIR-Institute of Genomics and Integrative Biology, South Campus, Mathura Road, New Delhi 110020, India.
authors.forename: Hemlata
authors.initials: H
authors.lastname: Gautam
authors.affiliation: CSIR-Indian Institute of Toxicology Research, Post Box 80, Mahatma Gandhi Marg, Lucknow (Uttar Pradesh) 226001, India.
authors.forename: Kausar M
authors.initials: KM
authors.lastname: Ansari
authors.affiliation: Delhi Technological University, Shahbad Daulatpur, Main Bawana Road, New Delhi 110042, India.
authors.forename: Deenan
authors.initials: D
authors.lastname: Santhiya
authors.affiliation: CSIR-Institute of Genomics and Integrative Biology, South Campus, Mathura Road, New Delhi 110020, India; Academy of Scientific and Innovative Research (AcSIR), Anusandhan Bhawan, 2 Rafi Marg, New Delhi 110001, India.
authors.forename: Vivek T
authors.initials: VT
authors.lastname: Natarajan
authors.affiliation: CSIR-Institute of Genomics and Integrative Biology, South Campus, Mathura Road, New Delhi 110020, India; Academy of Scientific and Innovative Research (AcSIR), Anusandhan Bhawan, 2 Rafi Marg, New Delhi 110001, India. Electronic address: mganguli@igib.res.in.
authors.forename: Munia
authors.initials: M
authors.lastname: Ganguli
mesh_terms: D000287:Administration, Topical; D000818:Animals; D002460:Cell Line; D002470:Cell Survival; D057846:Cell-Penetrating Peptides / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D005434:Flow Cytometry; D015870:Gene Expression; D018014:Gene Transfer Techniques; D017930:Genes, Reporter; D006801:Humans; D051379:Mice; D053758:Nanoparticles; D009696:Nucleic Acids / Q000008:administration & dosage / Q000737:chemistry / Q000235:genetics; D010539:Permeability; D010957:Plasmids / Q000008:administration & dosage / Q000737:chemistry / Q000235:genetics; D012827:Silicone Oils / Q000737:chemistry; D012867:Skin / Q000378:metabolism*; D017550:Spectroscopy, Fourier Transform Infrared; D014162:Transfection
chemical_list: D057846:Cell-Penetrating Peptides; D016207:Cytokines; C000611834:Mgpe9 peptide; D009696:Nucleic Acids; D012827:Silicone Oils
keywords: cell-penetrating peptide; nanocomplex; nucleic acid delivery; penetration enhancers; silicone oil; skin; topical; transfection