Recombinant scFv-Fc Anti-kallikrein 7 Antibody-Loaded Thermosensitive Hydrogels Against Skin Desquamation Disorders

ACS Appl Bio Mater. 2024 Jul 15;7(7):4486-4496. doi: 10.1021/acsabm.4c00371. Epub 2024 Jun 17.

Abstract

Human tissue kallikrein-related peptidase 7 (KLK7) is a serine protease implicated in the physiology of skin desquamation, and its uncontrolled activity can lead to chronic diseases such as psoriasis, atopic dermatitis, and Netherton syndrome. For this reason, kallikrein 7 has been identified as a potential therapeutic target. This work aimed to evaluate Pluronic (PL) hydrogels as topical carriers of four specific scFv-Fc antibodies to inhibit KLK7. The hydrogels comprised PL F127 (30% w/v) alone and a binary F127/P123 (28-2% w/v) system. Each formulation was loaded with 1 μg/mL of each antibody and characterized by physicochemical and pharmaceutical techniques, considering antibody-micelle interactions and hydrogel behavior as smart delivery systems. Results showed that the antibodies were successfully loaded into the PL-based systems, and the sol-gel transition temperature was shifted to high values after the P123 addition. The antibodies released from the gels preserved their rheological properties (G' > G'', 35- to 41-fold) and inhibitory activity against KLK7, even after 24 h. This work presented potential agents targeting KLK7 that may provide strategies for treating skin abnormalities.

Keywords: Pluronic; atopic dermatitis; hydrogel; kallikreins; scFv-Fc antibodies.

MeSH terms

  • Biocompatible Materials / chemistry
  • Biocompatible Materials / pharmacology
  • Humans
  • Hydrogels* / chemistry
  • Hydrogels* / pharmacology
  • Kallikreins* / antagonists & inhibitors
  • Kallikreins* / metabolism
  • Materials Testing
  • Particle Size
  • Poloxamer / chemistry
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / pharmacology
  • Single-Chain Antibodies / chemistry
  • Single-Chain Antibodies / pharmacology
  • Skin Diseases / drug therapy
  • Skin Diseases / pathology
  • Temperature

Substances

  • Hydrogels
  • Kallikreins
  • KLK7 protein, human
  • Single-Chain Antibodies
  • Biocompatible Materials
  • Poloxamer
  • Recombinant Proteins