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MP2
Formulation & Performance
Formulation & Performance
Study-specific compositions, preparation conditions and experimental outcomes for MP2.
User-supplied full article and publisher supplementary PDF reviewed, including local rectal delivery and chronic-colitis experiments.
1. Formulations and component amounts
Reported composition and calculated mass are separate. Molecular-weight inputs use the current catalog values; DMG-PEG2000 is fixed initially at 2507. Edit inputs only when using a verified alternative material.
MP2 LNP
molar parts (sum 90.75)Main Methods: LNP formulation
| Component | Molecular weight | Molar parts | Normalized mol% | Amount (µmol) | Weight (mg) |
|---|---|---|---|---|---|
| MP2 | 22.039 | 30.7010 | 39.1090 | ||
| DOPE | 33.058 | 46.0514 | 34.2636 | ||
| Cholesterol | 44.077 | 61.4019 | 23.7410 | ||
| DMG-PEG2000 | 0.826 | 1.1513 | 2.8863 |
Calculated total: 100.0000 mg lipid. RNA, solvent and process loss are excluded.
How component weights are calculated
For total lipid mass M (mg), molar parts rᵢ and molecular weight MWᵢ: component mass = M × rᵢ × MWᵢ / Σ(r × MW). Component amount (µmol) = component mass (mg) × 1000 / MWᵢ. Molar parts are normalized only for the displayed percentage. The calculation does not infer N/P or RNA dose.
2. Preparation and experimental setup
| Parameter | Reported procedure / limitation | Source |
|---|---|---|
| Assembly | Organic lipid solution and aqueous mRNA combined using a microfluidic mixer, followed by PBS dialysis. | Methods; solvent identity, buffer pH, phase ratio and total flow not specified in the reviewed passage |
| RNA ratio | Reported lipid:mRNA mass ratio 10:1; the passage does not explicitly identify total lipid versus ionizable lipid as the numerator. | Methods; not treated as N/P |
| Local delivery vehicle | All in vivo formulations were mixed with Pluronic F127 solution to prolong colonic residence. The concentration is not established in the reviewed passage. | Methods: in vivo delivery |
| Frozen-storage procedure | 10 wt% sucrose in Tris and liquid-nitrogen freezing are discussed separately from the dosing formulation. | Methods; do not assume the final rectal formulation has the same buffer composition |
3. Particle characterization
| Measurement / batch | Reported result | Evidence context |
|---|---|---|
| Composition convention | 20:30:40:0.75 is explicitly a molar ratio, not a 100% table | Methods |
| Physical properties | Individual particle-size / PDI values should be read for the corresponding formulation in Fig. 1 and SI | No single value is inferred for every MP2/cargo batch |
| Reporter versus therapeutic cargo | Fluc, GFP, Cre and IL-35 experiments are distinct | Main Figs. 1–5 |
4. Performance by experiment
| Experiment and dose | Readout and comparator | Result and source |
|---|---|---|
| Cell reporter screen Caco-2 cells; Fluc mRNA 0.5 µg/mL | Readout: 18 h Comparator: Benchmark lipid formulations in the screen | The screen identifies potent glucocorticoid-derived formulations. Reporter expression is a cell-assay endpoint, not colitis efficacy.Fig. 1; cell-transfection Methods |
| Rectal reporter delivery TNBS-colitis mice; Fluc mRNA; rectal 0.5 mg/kg with F127 | Readout: 6 h Comparator: SM-102 study formulation | MP2 produces approximately 15-fold greater reported colonic reporter expression. Helper composition also differs between formulations.Fig. 1; n=3 |
| Cell-type delivery Ai14 reporter mice; Cre mRNA; rectal 0.5 mg/kg on two consecutive days | Readout: Day 5 tissue assessment Comparator: Reporter controls | Recombined reporter expression maps transfected cell populations. Cre recombination is not an IL-35 therapeutic outcome.Main Fig. 2; Methods |
| Chronic colitis Female IL-10-knockout mice; IL-35 mRNA; rectal 1 mg/kg once weekly, starting at 11 weeks of age | Readout: Endpoint at 18 weeks of age Comparator: SM-102–IL-35 and other study arms | Reported disease activity index 0.38 for MP2–IL-35 versus 3.75 for SM-102–IL-35. This is an age-defined follow-up, not 18 weeks of treatment.Fig. 4; n=8; chronic-model Methods |
| Human tissue delivery Ex vivo IBD biopsy cultures; GFP mRNA 1 µg/well | Readout: 24 h Comparator: Ex vivo culture controls | Expression was detected across immune, epithelial and endothelial populations. This is tissue-culture evidence, not dosing of patients.Fig. 5; human-biopsy Methods |
| Human tissue immune response Ex vivo Crohn’s-disease biopsy cultures; MP2–IL-35 | Readout: Study ex vivo endpoint Comparator: Study culture controls | Reported changes include reduced Th1/Th17 populations and increased Treg populations. Donor and gating context is retained in the paper.Fig. 5; SI gating figures |
Mechanistic evidence
Uptake and galectin-9 membrane-damage assays were evaluated. Similar Caco-2 uptake does not by itself explain expression differences; uptake, endosomal disruption and the lipid’s own anti-inflammatory activity must be considered separately.
5. Interpretation and unresolved details
- The recipe total is 90.75 molar parts. The mass table normalizes these parts for calculation and does not change the reported recipe.
- The methylprednisolone-derived lipid may contribute pharmacological activity itself. IL-35 expression and steroid-derived effects cannot be assumed independent.
- The paper calls for further repeat-dose, metabolism and long-term tolerability work. Rectal mouse and ex vivo biopsy results do not establish systemic human efficacy.
Results apply to the stated LNP composition, cargo, process, dose, route and model. LNP experimental measurements are not batch-release specifications for the isolated lipid.
6. References and data access
Cao D, et al. Anti-inflammation lipid nanoparticles enable localized mRNA therapy for inflammatory bowel disease. Nature Communications (2026). doi:10.1038/s41467-026-78302-5
DOI: 10.1038/s41467-026-78302-5
Download experiment table (CSV) · Open printable Formulation & Performance guide
Revision FP-20261022 · Source review: 22 October 2026 · DC Chemicals