Scientific article

Erbium:YAG fractional laser ablation for the percutaneous delivery of intact functional therapeutic antibodies

Published inJournal of controlled release, vol. 156, no. 1, p. 53-59
Publication date2011

The physicochemical properties and stability requirements of therapeutic proteins necessitate their parenteral administration even for local therapy; however, unnecessary systemic exposure increases the risk of avoidable side-effects. The objective of this study was to use fractional laser ablation to enable the delivery of intact, functional therapeutic antibodies into the skin in vitro and in vivo. The laser-assisted delivery of Antithymocyte globulin (ATG) and Basiliximab - FDA-approved therapeutics for the induction of immunosuppression - was investigated. In vitro delivery experiments were performed using dermatomed porcine ear and human abdominal skins; an in vitro/in vivo correlation was shown using C57 BL/10 SCSnJ mice. Antibody transport was quantified by using ELISA methods developed in-house. Results showed that increasing the pore number from 300 to 450 and 900, increased total antibody delivery (sum of amounts permeated and deposited); e.g., for ATG, from 1.18±0.10 to 3.98±0.64 and 4.97±0.83 μg/cm(2), respectively - corresponding to 19.7-, 66.3- and 82.8-fold increases over the control (untreated skin). Increasing laser fluence from 22.65 to 45.3 and 135.9J/cm(2) increased total ATG delivery from 1.70±0.65 to 4.97±0.83 and 8.70±1.55 μg/cm(2), respectively. The Basiliximab results confirmed the findings with ATG. Western blot demonstrated antibody identity and integrity post-delivery; human lymphocyte cytotoxicity assays showed that ATG retained biological activity post-delivery. Immunohistochemical staining was used to visualize ATG distribution in the epidermis. Total ATG delivery across porcine ear and human abdominal skin was statistically equivalent and an excellent in vitro/in vivo correlation was observed in the murine model. Based on published data, the ATG concentrations achieved in the laser-porated human skins were in the therapeutic range for providing local immunosuppression. These results challenge the perceived limitations of transdermal delivery with respect to biopharmaceuticals and suggest that controlled laser microporation provides a less invasive, more patient-friendly "needle-less" alternative to parenteral administration for the local delivery of therapeutic antibodies.

  • Administration, Cutaneous
  • Animals
  • Antibodies, Monoclonal/administration & dosage/pharmacokinetics/pharmacology
  • Antilymphocyte Serum/administration & dosage/pharmacology
  • Cell Survival/drug effects
  • Drug Delivery Systems/instrumentation/methods
  • Enzyme-Linked Immunosorbent Assay
  • Humans
  • Immunohistochemistry
  • Lasers, Solid-State
  • Lymphocytes/drug effects
  • Mice
  • Mice, Inbred C57BL
  • Microscopy, Fluorescence
  • Porosity
  • Recombinant Fusion Proteins/administration & dosage/pharmacokinetics/pharmacology
  • Skin/metabolism
  • Skin Absorption
  • Swine
  • Tissue Distribution
Citation (ISO format)
YU, Jing, KALARIA, Dhaval, KALIA, Yogeshvar. Erbium:YAG fractional laser ablation for the percutaneous delivery of intact functional therapeutic antibodies. In: Journal of controlled release, 2011, vol. 156, n° 1, p. 53–59. doi: 10.1016/j.jconrel.2011.07.024
Main files (1)
Article (Published version)
ISSN of the journal0168-3659

Technical informations

Creation09/04/2012 12:39:00 PM
First validation09/04/2012 12:39:00 PM
Update time03/14/2023 5:40:51 PM
Status update03/14/2023 5:40:51 PM
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