Magainin-2vsGramicidin

Molecular Formula

C₁₁₄H₁₈₀N₃₀O₂₉S

Molecular Weight

2,466.9 g/mol (magainin-2); Pexiganan (MSI-78): ~2,500 Da

Half-Life

Plasma half-life: minutes (rapid proteolytic degradation by serum proteases); local tissue persistence in wound environment: hours at therapeutic concentrations

Bioavailability

Topical bioavailability: local tissue concentrations achieve bactericidal levels with 1-2% cream formulation; systemic bioavailability minimal — rapidly degraded by tissue proteases if absorbed; poor oral bioavailability

CAS Number

108433-95-0

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)

Common

• Application site burning/stinging
• Local erythema
• Mild pruritus
• Increased wound exudate

Uncommon

• Contact sensitization

Serious

• No serious systemic adverse effects documented

Common

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

Uncommon

• Superinfection

Serious

• Hemolytic toxicity with systemic absorption

Evidence Level

Moderate human trials (Phase 1-2)

FDA Status

Research compound

Safety Overview

Magainin-2 demonstrates favorable safety in topical antimicrobial wound care studies with minimal systemic absorption through intact skin. Local tissue irritation minimal at therapeutic concentrations (0.1-1% w/w); hemolytic activity negligible at concentrations <10 μM. No serious adverse events in Phase II wound healing trials. Peptide stability dependent on formulation pH; activity preserved at physiologic pH. Resistance development slower than traditional antibiotics.

Contraindications

• xKnown hypersensitivity to magainin peptides or amphibian-derived proteins
• xPregnancy and breastfeeding — insufficient safety data for magainin-derived therapeutics
• xDeep tissue infections requiring systemic antimicrobial therapy — topical magainin has limited tissue penetration depth
• xSevere peripheral vascular disease with non-viable tissue — antimicrobial peptides require viable tissue interface for effective action

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