LL-37 5mg vial

                                      NOT FOR HUMAN CONSUMPTION

LL-37 is the 37–amino-acid, C-terminal human cathelicidin peptide generated from the *CAMP* gene product hCAP18by proteolysis (e.g., proteinase-3). It is an amphipathic α-helical host-defense peptide (HDP) that combines direct, rapid microbicidal activity (bacteria, some fungi and enveloped viruses) with potent immunomodulation: chemotaxis, dendritic-cell licensing, angiogenesis, epithelial repair, endotoxin neutralization, and biofilm disruption. Unlike conventional antibiotics, LL-37 acts via membrane perturbation and immune signalling, reducing classical resistance pressure; however, organisms can adapt (surface charge remodeling, proteases). No LL-37 product is FDA/EMA-approved; several topical/inhaled candidates and analogs are in clinical development.

Additional Benefits of LL-37 Now Under Investigation

2. Molecular Mechanism of Action

2.1 Pharmacodynamics / Receptors

• Direct antimicrobial: Amphipathic helix inserts into microbial membranes → carpet/pore mechanisms → rapid lysis.

• Pattern neutralization: Binds LPS/LTA and nucleic acids, reducing TLR over-activation.

• Immunomodulation: Engages FPR2/ALX, P2X7, and transactivates EGFR on epithelia; chemoattracts neutrophils, monocytes, T cells; promotes angiogenesis.

• Autoimmunity context: Complexes with self-DNA/RNA can trigger pDC TLR9/7 and type-I IFN—implicated in psoriasis pathogenesis (caution in susceptible patients).

2.2 Down-stream Biology

3. Pharmacokinetics

• Route/formulations: Topical gels/creams, wound dressings, intranasal/inhaled aerosols; parenteral use is experimental.

• Half-life: Short minutes–hours in protease-rich environments (wounds, lung); activity extended by hydrogels, liposomes, PEGylation, D-amino-acid analogs, or cyclization.

• Distribution: Predominantly local at administration site; strong binding to GAGs and extracellular matrix.

• Clearance: Proteolysis (neutrophil elastase, trypsin-like proteases); minimal CYP involvement.

4. Pre-clinical and Translational Evidence

4.1 Chronic Wounds

Topical LL-37/analogs improved healing rates and time-to-closure in small RCTs of venous leg ulcers and pilot diabetic foot ulcer studies; reductions in bioburden and improved granulation were reported.

4.2 ENT / Respiratory

OP-145 (LL-37-derived) showed clinical signals in chronic suppurative otitis media; intranasal/inhaled candidates reduce pathogen burden and mucus viscosity in CF/bronchiectasis models.

4.3 Dentistry

Locally delivered LL-37 adjuncts improved clinical attachment level and reduced pathogen counts vs debridement alone in early trials.

4.4 Antiviral / ARI

In vitro inhibition of influenza and coronaviruses; small, phenotype-selected trials are exploring upper-airway symptom duration and viral load outcomes.

Evidence quality note: Many studies are early-phase/small; heterogeneity in peptide versions, delivery systems, and endpoints remains a limitation.

5. Emerging Clinical Interests

6. Safety and Tolerability

• Common (topical): Mild stinging, erythema, transient pruritus.

• Systemic/respiratory (investigational): Occasional cough/bronchial irritation with inhaled forms.

• Cytotoxicity window: High micromolar levels can injure host cells—necessitates controlled delivery.

• Autoimmune caution: LL-37–nucleic acid complexes may exacerbate psoriasis/lupus-like pathways in predisposed individuals.

• Microbiome: More sparing than broad antiseptics; resistance risk exists (charge remodeling, proteases) but is lower/different than for antibiotics.

Comparative safety matrix

7. Regulatory Landscape

• Approvals: None (major markets).

• Clinical programs: Topical gels/dressings and inhaled/nasal formulations in early trials; LL-37-derived analogs(e.g., OP-145, SAAP-class) advancing as antibiofilm agents.

• Manufacturing: Peptide synthesis under GMP; stability and protease susceptibility drive formulation innovation.

8. Future Directions

• Formulation engineering: Protease-resistant analogs, nanocarriers, and smart hydrogels for sustained local delivery.

• Phenotype-guided trials: Target biofilm-heavy, chronic wounds, CF bronchiectasis, and recalcitrant sinus disease with standardized biofilm endpoints.

• Combination therapy: Synergy with β-lactams/vancomycin/quinolones to shorten courses and curb resistance.

• Biomarker strategy: Measure LPS-neutralization, cytokine signatures, and microbiome shifts alongside clinical outcomes.

• Safety focus: Screen for autoimmune flare risk (psoriasis history), optimize local dosing windows.

Selected References

• Antimicrobial Agents & Chemotherapy; Journal of Antimicrobial Chemotherapy — Antimicrobial and antibiofilm profiles, synergy with antibiotics.

• Infection & Immunity; Shock — Endotoxin/LTA neutralization and cytokine modulation.

• Wound Repair & Regeneration; The Lancet EBioMedicine — Clinical signals in venous/diabetic ulcers and tissue repair mechanisms.

• American Journal of Respiratory Cell and Molecular Biology; Thorax — Airway defence and inhaled peptide studies.

• Journal of Clinical Periodontology; Journal of Periodontal Research — Periodontal adjunctive therapy data.

• Investigative Ophthalmology & Visual Science; Cornea — LL-37 analogs in corneal infection/repair.

• Nature Communications; Journal of Immunology — FPR2/ALX signalling, immune tuning, NET biology.

• Cancer Research; Oncogene — Context-dependent oncologic roles and tumor-selective analog development.