Defensin (HBD-2)vsDefensin (HBD-3)

Molecular Formula

Approximately C₁₈₅H₂₉₀N₅₄O₅₇S₆ (₄₁-amino acid peptide with ₃ disulfide bonds)

Molecular Weight

~4,328 Da (mature peptide)

Half-Life

Short plasma half-life (minutes); locally stable at wound and epithelial sites due to disulfide-bonded structure; degraded by metalloproteinases in chronic wound environments

Bioavailability

Topical application provides local antimicrobial activity; three disulfide bonds confer resistance to proteolytic degradation; salt-sensitive — activity reduced above 150 mM NaCl; not intended for oral or systemic delivery

CAS Number

Not assigned (endogenous human peptide; research-grade available from multiple suppliers)

Molecular Formula

Approximately C₂₂₀H₃₄₀N₆₄O₆₂S₆ (₄₅-amino acid peptide with ₃ disulfide bonds)

Molecular Weight

~5,155 Da (mature peptide)

Half-Life

Short systemic half-life (minutes) typical of cationic peptides; disulfide-bonded form provides protease resistance at local tissue sites; linear form shows adequate stability for topical applications

Bioavailability

Topical application achieves high local concentrations; maintains activity in physiological salt environments (unique); linear form retains activity enabling simplified formulation; not intended for oral or systemic delivery

CAS Number

Not assigned (endogenous human peptide; research-grade available from peptide suppliers)

Common

• Local site irritation
• Transient inflammatory response
• Reduced activity in saline environments

Uncommon

• Localized allergic reaction
• Inflammatory amplification

Serious

• No serious adverse effects documented

Common

• Local site irritation
• Transient inflammatory response
• Mild wound bed changes

Uncommon

• Localized allergic reaction
• Mild cytotoxicity at high concentrations

Serious

• No serious adverse effects documented at therapeutic concentrations

Evidence Level

Moderate human trials (Phase 1-2)

FDA Status

Research compound

Safety Overview

Defensin HBD-2 is not FDA-approved and has no completed human clinical trials, with all safety data limited to in vitro mechanistic studies and animal models. Animal toxicology studies show no significant systemic toxicity or organ damage at doses exceeding therapeutic levels. However, human immunological responses to exogenously administered antimicrobial peptides are not fully characterized. Concerns exist regarding potential immune activation, cross-reactivity with self-antigens, and development of antibodies to the synthetic peptide. Bacterial resistance development to defensin-based therapeutics is theoretically possible. No human pharmacokinetics, dose-escalation studies, Phase 1 safety data, or clinical efficacy trials have been conducted.

Contraindications

• xKnown hypersensitivity to defensin peptides or formulation components
• xPregnancy and breastfeeding — insufficient safety data for exogenous defensin administration
• xActive autoimmune skin conditions where defensin overexpression may contribute to pathology (e.g., psoriasis flare)
• xCystic fibrosis patients — elevated airway NaCl concentrations inactivate HBD-2 antimicrobial activity

Evidence Level

Moderate human trials (Phase 1-2)

FDA Status

Research compound

Safety Overview

Defensin HBD-3 is not FDA-approved and has no completed human clinical trials, existing only in research contexts with in vitro and animal study data. Animal toxicology studies demonstrate no major systemic toxicity at doses exceeding therapeutic levels, but human immunological responses to exogenously administered defensin peptides have not been characterized. Risks include potential immune activation, cross-reactivity with self-antigens (due to HBD-3 expression in healthy epithelial cells), development of anti-peptide antibodies, and possible tolerance development with repeated dosing. Bacterial and fungal resistance to defensin-based therapy is theoretically possible. No human pharmacokinetics, dose-ranging studies, Phase 1 safety assessments, or clinical efficacy data exist.

Contraindications

• xKnown hypersensitivity to defensin peptides or formulation components
• xPregnancy and breastfeeding — insufficient safety data for exogenous defensin administration
• xActive autoimmune conditions — potential for immune activation through monocyte/macrophage recruitment
• xSevere hepatic or renal impairment — peptide clearance may be altered for any systemic exposure