Defensin (HBD-2)vsLL-37

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

C₂₀₅H₃₄₀N₆₀O₅₃

Molecular Weight

4,493.26 Da

Half-Life

Short systemic half-life (minutes) due to protease susceptibility; local tissue persistence at wound sites is longer due to binding to extracellular matrix components and lipid membranes

Bioavailability

Topical application achieves high local wound-bed concentrations; systemic bioavailability limited by rapid proteolytic degradation and serum protein binding; not intended for oral delivery

CAS Number

154947-66-7

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 stinging or burning
• Mild perilesional erythema
• Increased wound exudate

Uncommon

• Allergic contact reaction

Serious

• Hemolytic activity at systemic 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

LL-37 is an endogenous cathelicidin antimicrobial peptide naturally produced by immune cells and epithelial tissues, conferring inherent biocompatibility and low toxicity at physiological concentrations. Synthetic LL-37 shows excellent safety in in vitro immune assays and animal models with no hepatotoxicity, nephrotoxicity, or genotoxicity at relevant doses. At elevated concentrations, the cationic amphipathic structure can cause hemolysis and cell membrane damage, but therapeutic doses are far below these thresholds. Injection site reactions are minimal in research applications.

Contraindications

• xKnown hypersensitivity to cathelicidin peptides or formulation components
• xActive hemolytic conditions — LL-37 demonstrates concentration-dependent hemolytic activity
• xPregnancy and breastfeeding — insufficient reproductive safety data from clinical trials
• xSevere renal impairment — peptide clearance may be altered