Properties and Application of Recombinant Human Lactoferrin to Enhance Healing of Diabetic Wounds

J. Engelmayer, PhD, MBA; A. Varadhachary, MD, PhD

Disclosures

Wounds. 2003;15(9) 

In This Article

Abstract and Introduction

Lactoferrin (LF) is a naturally occurring protein found in mammalian exocrine secretions, such as milk, with broad immunomodulatory, anti-inflammatory, and anti-infective properties. Recent in-vitro and in-vivo studies suggest that LF also promotes wound healing. Recombinant human lactoferrin (rhLF), which is identical to native human LF in all material respects, is being produced in large quantities as a pharmaceutical grade material and is currently in phase 2 clinical trials. rhLF appears to be safe and well tolerated in animal and clinical studies and holds out promise as a novel agent for the treatment of diabetic ulcers.

Lactoferrin (LF) is a member of the transferrin family of nonheme iron-binding proteins.[1] LF is found mainly in external secretions of mucosal epithelia, such as milk, saliva, tears, seminal fluid, sweat, and nasal mucus, as well as in bile, pancreatic fluid, and intestinal secretions in mammals. LF is also found in the secondary granules of neutrophils, which are the main source of LF in plasma as it is secreted upon neutrophil stimulation. As shown in Table 1 , several physiological functions, such as broad-spectrum anti-infective, immunomodulatory, and anti-inflammatory activities, have been attributed to LF.[2,3]

Pharmaceutical grade recombinant human lactoferrin (rhLF), produced in Aspergillus niger var. awamori, is a 78,000 Dalton glycoprotein and is identical in all material respects to its natural counterpart, native lactoferrin (LF).[4,5] rhLF is a 692-amino acid glycoprotein with a molecular weight of approximately 80 kDaltons. The protein has two lobes, each containing a binding site for ferric iron (Fe3+).[6] rhLF is structurally equivalent to native human LF, as demonstrated by a comparison of the three-dimensional structure, molecular weight, biological activity, and other physicochemical properties, and differs only in the nature of glycosylation.[7]

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