GramicidinvsLL-37

Molecular Formula

C₉₉H₁₄₀N₂₀O₁₇ (gramicidin A)

Molecular Weight

1,882.3 Da (gramicidin A); Gramicidin D mixture: ~1,880-1,900 Da average

Half-Life

Local tissue persistence: hours to days at topical application sites (protease-resistant D-amino acid structure); systemic half-life: not applicable (hemolytic — never administered systemically); single channel lifetime: ~1 second (open/close kinetics in electrophysiology)

Bioavailability

Topical: local tissue concentrations at application site; systemic absorption negligible through intact skin and eye; oral bioavailability: not applicable (not used orally for systemic effect; would cause GI hemolysis); intrinsically resistant to proteases due to D-amino acid content

CAS Number

11029-61-1 (gramicidin A); 1405-97-6 (gramicidin D mixture)

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

• Ophthalmic stinging/burning
• Local skin irritation
• Temporary blurred vision
• Contact sensitization

Uncommon

• Superinfection

Serious

• Hemolytic toxicity with systemic absorption

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

Gramicidin is a cyclic peptide antibiotic derived from Bacillus brevis with a 70+ year track record of topical safety. It functions as a pore-former in bacterial membranes and shows minimal systemic absorption when applied to intact skin or mucous membranes, making it extremely low-toxicity for localized use. The primary safety concern is sensitization reactions in 1-5% of users with prolonged exposure, not organ toxicity. Gramicidin is FDA-approved for topical antibacterial applications and generally well-tolerated across age groups.

Contraindications

• xKnown hypersensitivity to gramicidin or any component of topical/ophthalmic formulations
• xSystemic administration by any route — gramicidin is hemolytic and toxic to red blood cells; strictly topical/ophthalmic use only
• xDeep puncture wounds or severe burns requiring systemic antimicrobial coverage
• xProlonged use on large open wounds — even topical gramicidin may cause hemolysis if absorbed systemically through extensive denuded skin

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