Defensin (HBD-3)vsLL-37

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)

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
• Mild wound bed changes

Uncommon

• Localized allergic reaction
• Mild cytotoxicity at high concentrations

Serious

• No serious adverse effects documented at therapeutic concentrations

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-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

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