NisinvsLL-37

Molecular Formula

C₁₄₃H₂₃₀N₄₂O₃₇S₇

Molecular Weight

3,354.12 Da

Half-Life

Rapidly degraded in GI tract by digestive proteases; stable for hours to days in food matrices at acidic pH; lanthionine ring structures resist most environmental proteases; thermostable (survives pasteurization)

Bioavailability

Degraded by pancreatic proteases in GI tract (does not affect gut microbiome at dietary levels); topical application achieves effective local concentrations; optimal activity at pH 2-6; lanthionine bridges provide significant protease resistance compared to linear peptides

CAS Number

1414-45-5

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

• No significant effects at dietary levels
• Mild GI discomfort at research doses
• Local irritation (topical use)

Uncommon

• Milk protein allergic reaction
• Gram-negative overgrowth

Serious

• No documented serious adverse effects

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

Strong human trials (Phase 3 or FDA approved)

FDA Status

FDA approved for this use

Safety Overview

Nisin holds FDA GRAS status since 1988 with over 50 years of documented safe human consumption, making it the only antimicrobial peptide with this comprehensive long-term safety record. Oral LD50 of 174 mg/kg in mice (comparable to table salt) demonstrates extraordinary safety margin. Acceptable daily intake established at 0.13 mg/kg body weight with no reported serious adverse events at this or higher levels. Primary risk is milk protein contamination during production, requiring screening for lactose-intolerant or milk-allergic individuals.

Contraindications

• xKnown hypersensitivity to nisin or Lactococcus lactis-derived products
• xMilk protein allergy — nisin production involves dairy-associated bacteria and preparations may contain trace milk proteins
• xPregnancy and breastfeeding at therapeutic (non-dietary) doses — standard dietary exposure through preserved foods is considered safe
• xActive inflammatory bowel disease — potential for local irritation at high oral concentrations exceeding normal dietary levels

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