Jing Yu1,2, Sachin Dubey2,3, Yogeshvar N Kalia2. 1. a State Key Laboratory of Microbial Metabolism, Sheng Yushou Center of Cell Biology and Immunology, Department of Genetics and Developmental Science, School of Life Sciences and Biotechnology , Shanghai Jiaotong University , Shanghai , China. 2. b School of Pharmaceutical Sciences , University of Geneva & University of Lausanne , Geneva , Switzerland. 3. c Glenmark Pharmaceuticals SA , La Chaux de Fond , Switzerland.
Abstract
BACKGROUND: Dermatological diseases, including most skin cancers and rare genetic conditions frequently originate in the epidermis. Targeted, topical cell-based therapy is a promising therapeutic strategy. Here, we present the first report demonstrating that fractional laser ablation enables local 'needle-free' intraepidermal delivery of living human cells. METHODS: The cells penetrated porcine ear skin via microchannels created by Er:YAG fractional laser ablation; cell delivery was quantified using a haemocytometer. Cutaneous distribution was confirmed visually by laser scanning confocal microscopy and histological analysis. RESULTS: Total cell delivery (sum of amounts permeated and deposited) after 24 h increased from 5.7 ± 0.1 x105 to 9.6 ± 1.6 x105 cells/cm2 when increasing pore density from 300 to 600 pores/cm2, - corresponding to 19- and 32-fold increases over the control. At 600 pores/cm2, cell deposition was 136-fold greater than cell permeation - the latter most likely due to transport from micropores into appendageal pathways. Production of GFP post-delivery confirmed cell remained viability. CONCLUSION: The results demonstrate the feasibility of using controlled laser microporation to achieve local 'needle-free' cutaneous delivery of living human cells to the epidermis and dermis. This raises the possibility of using this technique for targeted new approaches for dermatological therapy in these regions.
BACKGROUND: Dermatological diseases, including most skin cancers and rare genetic conditions frequently originate in the epidermis. Targeted, topical cell-based therapy is a promising therapeutic strategy. Here, we present the first report demonstrating that fractional laser ablation enables local 'needle-free' intraepidermal delivery of living human cells. METHODS: The cells penetrated porcine ear skin via microchannels created by Er:YAG fractional laser ablation; cell delivery was quantified using a haemocytometer. Cutaneous distribution was confirmed visually by laser scanning confocal microscopy and histological analysis. RESULTS: Total cell delivery (sum of amounts permeated and deposited) after 24 h increased from 5.7 ± 0.1 x105 to 9.6 ± 1.6 x105 cells/cm2 when increasing pore density from 300 to 600 pores/cm2, - corresponding to 19- and 32-fold increases over the control. At 600 pores/cm2, cell deposition was 136-fold greater than cell permeation - the latter most likely due to transport from micropores into appendageal pathways. Production of GFP post-delivery confirmed cell remained viability. CONCLUSION: The results demonstrate the feasibility of using controlled laser microporation to achieve local 'needle-free' cutaneous delivery of living human cells to the epidermis and dermis. This raises the possibility of using this technique for targeted new approaches for dermatological therapy in these regions.
Authors: Aditya R Darade; Maria Lapteva; Thomas Hoffmann; Markus Mandler; Achim Schneeberger; Yogeshvar N Kalia Journal: Pharmaceutics Date: 2022-01-08 Impact factor: 6.321
Authors: Martin Bauer; Edith Lackner; Peter Matzneller; Valentin Al Jalali; Sahra Pajenda; Vincent Ling; Christof Böhler; Werner Braun; Reinhard Braun; Maximilian Boesch; Patrick M Brunner; Markus Zeitlinger Journal: Front Med (Lausanne) Date: 2021-07-16