Tissue peptides
LL-37 (human cathelicidin antimicrobial peptide)
Also known as LL37, cathelicidin LL-37, hCAP18-derived LL-37, cathelicidin antimicrobial peptide
Endogenous host-defense (antimicrobial) peptide; investigational, not FDA-approved
Not FDA-approved. Not on FDA's 503A category lists (May 14, 2026). Source, May 14, 2026
Identity. LL-37 is the 37-amino-acid C-terminal fragment of human cathelicidin (hCAP18). A cited case report describes it as 'a naturally occurring 37-amino-acid peptide that is part of the innate immune system in human skin'. The human trials below used synthetic LL-37 as a topical solution or cream, not a subcutaneous injection. The formulary vial (5 mg) is a different dosage form from every studied product. The injectable practice doses below have no trial behind them. Intratumoral oncology exposure (250-500 ug per tumor, weekly) is a different route, indication and population. Do not use it to bound or justify the practice dose. FDA also flags peptide-related impurities and API characterization complexities, so product identity and purity depend on the dispensing pharmacy's certificate of analysis.
At a glance
These dosages are a helpful guide, not a prescription. Every clinician is expected to do their own due diligence before prescribing.
Start
0.5 mg/mL, topical application to venous leg ulcer1
Human study
Dosing detail
Human studies
Human studyHard-to-heal venous leg ulcers; first-in-man randomized double-blind, placebo-controlled dose-response trial (three LL-37 concentrations vs placebo)
0.5, 1.6, 3.2 mg/mL1
- Route
- Topical application to ulcer
- Frequency
- Twice weekly
- Duration
- 4-week randomized treatment phase (after 3-week placebo run-in), then 4-week follow-up
- n
- 34
- Design
- Randomized, double-blind, placebo-controlled dose-ranging
Source quote
The healing rate constants for 0.5 and 1.6 mg/mL of LL-37 were approximately six- and threefold higher than for placebo (p = 0.003 for 0.5 mg/mL and p = 0.088 for 1.6 mg/mL). | No difference in healing was observed between the groups receiving 3.2 mg/mL of LL-37 and placebo.
Finding. Healing rate constant about 6-fold (0.5 mg/mL, p=0.003) and 3-fold (1.6 mg/mL, p=0.088, not significant) higher than placebo; no difference at 3.2 mg/mL. Small exploratory trial; the signal was not reproduced in the full phase IIb population. No local or systemic safety concerns reported.
Hard-to-heal venous leg ulcers on compression therapy; phase IIb HEAL LL-37 trial
0.5, 1.6 (12.5 and 40 per cm2 ulcer area respectively) mg/mL (solution); ug/cm2 (active dose)2
- Route
- Topical, applied to wound bed
- Frequency
- Twice weekly (every 3 +/- 1 days)
- Duration
- 13 weeks
- n
- 148 treated (149 randomized)
- Design
- Multicentre, double-blind, randomized, placebo-controlled, phase IIb; allocation 1:1:1.
Source quote
at concentrations 0.5 or 1.6 mg/mL of LL-37 and active doses of 12.5 and 40 μg/cm2, respectively | All treatments were applied twice weekly (every 3 ± 1 days) | After randomization, participants received placebo or active treatment for a period of 13 weeks.
Finding. No significant healing improvement in the full population versus placebo; post hoc subgroup with ulcers of at least 10 cm2 improved. Well tolerated.
Diabetic foot ulcer with mild infection; LL-37 cream versus placebo cream (Jakarta)
0.5 (cream concentration); 0.025 mL cream per cm2 mg/g; mL/cm23
- Route
- Topical cream
- Frequency
- Twice a week
- Duration
- 4 weeks
- n
- 25 (13 LL-37, 12 placebo)
- Design
- Randomized, double-blind, placebo-controlled.
Source quote
to reach an LL-37 concentration of 0.5 mg/g | The cream requirement for each participant in both groups was 0.025 mL/cm2 | twice a week for 4 weeks
Finding. Granulation index increase was consistently greater with LL-37 cream; no effect on IL-1alpha, TNF-alpha or bacterial colonization. One mild irritant contact dermatitis in the LL-37 group.
Advanced melanoma; phase 1/2 intratumoral LL-37 (NCT02225366, registry record). Oncology exposure, different route and population; not usable to set subcutaneous dosing.
250 (cohort 1), 500 (cohort 2) ug per tumor4
- Route
- Intratumoral injection into 2-4 tumors
- Frequency
- Once a week
- Duration
- Up to 8 weeks
- n
- 4 enrolled (3 reported in results)
- Design
- Phase 1/2 dose-escalation; status completed. Registry lists 4 enrolled but results report 3 participants (2 in cohort 1, 1 in cohort 2).
Source quote
starting dose of 250 ug/tumor injection once a week | 500 ug/tumor injection once a week | One (1) time a week for 8 weeks, LL37 will be injected into 2-4 tumors.
Finding. No deaths or serious adverse events reported. Other adverse events are listed under safety. Causality not established.
What clinics and vendors publish
These ranges come from clinic and vendor publications, not studies.
No peer-reviewed review, non-commercial prescriber protocol, textbook, or controlled trial of subcutaneous LL-37 was identified. The practice numbers come from two information pages that carry vendor or supplier-referral banners, a publisher page that states the doses are not derived from dose-ranging studies, and a community wiki that calls them anecdotal. Treat them as unvalidated community convention. All human trial doses are topical and cannot be converted to a subcutaneous dose.
- StartCommunity-reported
- 50 mcg/day
- TypicalCommunity-reported
- Roughly 100 mcg per day (50-100 mcg/day conservative; 100 mcg/day most cited)
- CeilingCommunity-reported
- 200-300 mcg/day quoted for short courses only; no source supports a safe ceiling
- FrequencyCommunity-reported
- Sources disagree: once daily (7 days/week) per two pages; once daily 5 days/week per a third community wiki (100-200 mcg). None are trial-derived.
- RouteCommunity-reported
- Subcutaneous injection
- TimingCommunity-reported
- Morning or early afternoon (one source)
- CycleCommunity-reported
- 4 weeks on, 2 weeks off (one information page); 2-4 week runs (second page)
This involves starting at a lower dose (e.g., 50 mcg daily) and gradually increasing if the treatment is well tolerated.
4 weeks of active treatment | 2 weeks of washout (no treatment)
Inject in the morning or early afternoon with proper site rotation to minimize local reactions.
roughly 100 mcg per day subcutaneously, sometimes quoted up to 300 mcg, for short runs of two to four weeks.
They are not derived from dose-ranging studies.
100-200 mcg daily (SC); topical per formulation | Once daily, 5 days per week (SC); as directed (topical) | Based on anecdotal protocols; no established human SC dosing from clinical trials
Safety
Serious warnings
- FDA safety-risk page: 'FDA lacks sufficient safety-related information regarding cathelicidin LL-37'.9
- FDA safety-risk page: 'Compounded drugs containing cathelicidin LL-37 may pose risk for immunogenicity for certain routes of administration'.9
- FDA safety-risk page: 'Nonclinical research findings suggest detrimental effects on male reproduction'; the page also says LL-37 'can be protumorigenic in some tissues'.9
- Case report: in a melanoma patient given 8 weekly intratumoral LL-37 injections, verrucous papules and a vesiculo-bullous lesion with atypical squamous proliferation appeared about 45 days after starting; all lesions resolved within 2 months of stopping. A possible cutaneous class signal to watch for.10
Contraindications
- Avoid in psoriasis and other autoimmune or autoinflammatory disease (including SLE-type disease). Mechanistic basis, not label-derived: LL-37 binds self-DNA and self-RNA and converts them into triggers of plasmacytoid and myeloid dendritic cell activation (TLR9, TLR7, TLR8), and self-RNA-LL37 complexes are present in psoriatic skin lesions. No injected-LL-37 outcome data in autoimmune patients exist.11
- Avoid in active malignancy or recent cancer history, particularly ovarian, breast and lung. Preclinical and FDA-statement basis, not label-derived: LL-37 stimulates proliferation, migration and invasion of cancer cells in vitro, overexpression accelerates tumor growth in vivo, neutralizing LL-37 reduced ovarian xenograft growth, and FDA states LL-37 'can be protumorigenic in some tissues'.12
- Not studied: pregnancy, lactation, pediatrics, and men trying to conceive (FDA cites nonclinical male reproductive effects). No label contraindications exist.9
- One non-peer-reviewed page calls 'psoriasis, rosacea and lupus' 'reasonable contraindications on mechanistic grounds' (opinion, not trial-derived). A community wiki says 'Avoid in autoimmune conditions where immune stimulation may cause flares'. Neither source is peer reviewed.7
Adverse effects
- Phase IIb topical trial: 'The study drug was well tolerated and safe in both dose strengths.' 12 non-fatal serious adverse events in 11 patients (7.4%), none assessed as related to study drug.2
- First-in-man topical trial: 'There were no safety concerns regarding local or systemic adverse events.'1
- Diabetic foot ulcer cream trial: no side effect directly caused by the cream; 1 of 13 in the LL-37 group had mild irritant contact dermatitis.3
- NCT02225366 (intratumoral LL-37, 250-500 ug/tumor weekly, advanced melanoma): reported adverse events included squamous cell carcinoma, actinic keratosis, skin hypopigmentation, hypothyroidism and anemia (cohort 1, n=2; SCC and actinic keratosis each 1 of 2) and anemia, lymphocyte count decrease, white blood cell decrease and blood bilirubin increase (cohort 2, n=1). No deaths or serious adverse events reported. Causality not established; advanced melanoma population with prior therapy. Reinforces the single-case skin signal in the case report.4
- Injection-related effects reported on a non-peer-reviewed page: 'Reported effects are mostly local: stinging on injection, a red raised weal, itching'.7
Monitoring
- This plan is derived from the cited case report and registry adverse events. No source publishes a monitoring protocol, and no laboratory monitoring has been validated. Do a baseline and periodic full-skin exam for new verrucous, bullous or atypical lesions, especially from about week 4-6 (stop and biopsy if they appear). Take a baseline autoimmune history and review for flares during the course. Confirm age-appropriate cancer screening status before starting. Watch for injection-site reactions.10
Handling
Reconstitution
No source gives a validated diluent volume. Community sources disagree on dilution and one says to use bacteriostatic water. Dose in mcg, never in mg, and confirm concentration on the dispensing pharmacy's label. Worked arithmetic for a 5 mg (5,000 mcg) vial, not a sourced recommendation: at 1 mL diluent (5,000 mcg/mL) a 100 mcg dose is 0.02 mL; at 2 mL (2,500 mcg/mL) it is 0.04 mL; at 5 mL (1,000 mcg/mL) it is 0.1 mL. At 100 mcg/day the vial holds about 50 doses. At small volumes a modest syringe-reading error produces a 2x or larger dosing error.
Storage before mixing
Community source only (not a beyond-use date): lyophilized peptide at -20 C for long-term storage.
Storage after mixing
Community source only (not a beyond-use date): refrigerate at 2-8 C and use within 2-3 weeks. Defer to the dispensing pharmacy's beyond-use date.8
Evidence
No human data exist for subcutaneous LL-37, the route of the formulary vial. Human trials are topical only: a 34-patient phase I/II and a 148-patient phase IIb venous leg ulcer trial, plus a 25-patient diabetic foot ulcer cream trial. The phase IIb trial found no significant healing benefit in the full population. The only injected human exposure is a 4-patient intratumoral melanoma study (NCT02225366). FDA states it lacks sufficient safety information and notes possible pro-tumorigenic effects.
Mechanism
Host-defense peptide with antimicrobial activity. A cited trial reports that it 'induces angiogenesis, and keratinocyte migration and proliferation'. In oncology studies, intratumoral injection is described as stimulating the innate immune system through activation of plasmacytoid dendritic cells. The same LL-37 to nucleic-acid to pDC/TLR pathway is implicated in psoriatic autoimmune activation. The mechanism of systemic subcutaneous use has not been established in humans.3101113
Availability
Amounts offered
- 5 mg
Custom strengths on request.
References
According to PubMed
- 1Treatment with LL-37 is safe and effective in enhancing healing of hard-to-heal venous leg ulcers: a randomized, placebo-controlled clinical trial.Wound Repair Regen 2014;22(5):613-21, 2014
- 2Evaluation of LL-37 in healing of hard-to-heal venous leg ulcers: A multicentric prospective randomized placebo-controlled clinical trial.Wound Repair Regen 2021;29(6):938-950 (PMC9298190), 2021
- 3Efficacy of LL-37 cream in enhancing healing of diabetic foot ulcer: a randomized double-blind controlled trial.Arch Dermatol Res 2023;315(9):2623-2633 (PMC10514151), 2023
- 4Induction of Antitumor Response in Melanoma Patients Using the Antimicrobial Peptide LL37 (NCT02225366)ClinicalTrials.gov registry record
- 5LL-37 Antimicrobial Peptide Dosage Charts and CalculatorAllAboutPeptides.com; author Dr. Michael Fortunato, MD; last updated October 29, 2025; page carries a third-party vendor banner, 2025
- 6LL-37 DosingPeptides.wiki; author and date not stated; page carries a supplier referral banner, 2026
- 7LL-37 Peptide: Dosage, Protocols, Evidence & Legal Status (2026) | Peptide DossierPeptide Dossier (Gangotri46 Ventures LLC); author and date not stated, 2026
- 8LL-37 dosing | Peptide Protocol WikiPeptide Protocol Wiki, community wiki; author and date not stated, 2026
- 9Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety RisksU.S. FDA (content current as of 04/22/2026), 2026
- 10Dermatologic toxicity from novel therapy using antimicrobial peptide LL-37 in melanoma: A detailed examination of the clinicopathologic features.J Cutan Pathol 2018;45(7):539-544, 2018
- 11Plasmacytoid dendritic cells sense self-DNA coupled with antimicrobial peptide.Nature 2007;449(7162):564-9, 2007
- 12Leucine leucine-37 uses formyl peptide receptor-like 1 to activate signal transduction pathways, stimulate oncogenic gene expression, and enhance the invasiveness of ovarian cancer cells.Mol Cancer Res 2009;7(6):907-15, 2009
- 13Self-RNA-antimicrobial peptide complexes activate human dendritic cells through TLR7 and TLR8.J Exp Med 2009;206(9):1983-94, 2009
- 14The pro-inflammatory peptide LL-37 promotes ovarian tumor progression through recruitment of multipotent mesenchymal stromal cells.Proc Natl Acad Sci U S A 2009;106(10):3806-11, 2009
Last reviewed 2026-10-14. 33 figures checked against their sources. How this works