Lipid Nanoparticles (LNPs) protect payloads like mRNA/siRNA and enable cytosolic delivery. Creative Biolabs offers end-to-end LNP formulation/optimization for nucleic acids and small molecules, focusing on precision delivery and extrahepatic targeting for cancer, infectious diseases, and rare genetic disorders.
It leverages ML to speed up lead selection, uses targeted surface modification, conquers the IVIVC gap, ensures superior stability/efficacy, minimizes toxicity and risk, shortens development cycles and time-to-market, solving poor lab-animal study correlation and non-liver targeting issues.
Discover How We Can Help - Request a ConsultationThe core functionality of an LNP relies on the ionizable lipid. At the neutral pH of the bloe microscope to evaluate the transfection ability of LNP preparations.odstream, this lipid is uncharged, providing stability and low toxicity. Upon cellular uptake via endocytosis, the LNP enters the endosome, where the lower, acidic pH causes the ionizable lipid to become protonated (positively charged). This charge destabilizes the endosomal membrane, facilitating the endosomal escape and releasing the therapeutic payload (mRNA, siRNA, or small molecule) into the cytoplasm, where it can be translated or act on its target.
Fig.1 mRNA lipid nanoparticles consist of representative lipids for therapeutic nucleic acid delivery, with structures including multi-layered vesicles, nanostructured-core particles, or homogeneous core-shell structures.1,3
Precision Targeting: Ligand/antibody functionalization enables specific cell-level delivery (e.g., splenic DCs, T-cells), moving beyond common passive liver uptake.
Enhanced Stability: Optimized lipid ratios and PEG-lipid selection boost shelf stability and circulation time, reducing reliance on ultra-cold chain storage.
Safety by Design: Careful ionizable lipid selection and controlled manufacturing manage inherent adjuvanticity, lowering unwanted inflammatory side effects.
Superior Encapsulation: Systematic component screening achieves >90% encapsulation efficiency for diverse payloads, minimizing waste and maximizing dose uniformity.
Targeted LNP Synthesis Services further enhance this process by engineering surface ligands that guide LNPs to specific cell types, ensuring payload delivery is both efficient and precisely localized.
Creative Biolabs' approach to LNP development is built on a clear, systematic framework, ensuring predictable outcomes and a clear path to regulatory submission.
Virtual screening of thousands of core LNP component combinations (ionizable lipid, helper lipid, cholesterol, PEG-lipid) is done via multivariate analysis and ML, based on payload properties (solubility, pKa, size). It replaces tedious traditional screening, identifying the top 5-10 leads with optimally predicted encapsulation efficiency and stability.
Lead formulations are produced via high-precision microfluidics, strictly controlling CQAs (particle size <100 nm, PDI < 0.1). Delivers verified leads for biological testing and complete physicochemical characterization reports.
Rigorous biological testing exceeds simple immortalized cell lines. Evaluates LNP adjuvanticity and immune activation (TLR4/CD1d binding) to engineer controlled immune profiles, down-selecting top 1-3 candidates based on predictive clinical relevance (not just basic in vitro performance).
For extrahepatic delivery, the top candidate's PEG-lipid layer is functionalized with ligands/antibodies/peptides for targeted uptake by desired cells (e.g., T-cells, DCs) or tissues (e.g., lung), yielding specialized LNPs for precise delivery to hard-to-reach tissues.
The typical timeframe for systematic LNP formulation ranges from 10 to 16 weeks, depending on the complexity of the payload (e.g., novel ionizable lipid synthesis for extrahepatic targeting can extend the duration) and the required scope of in vivo validation.
Creative Biolabs provides modular services designed to fit any stage of your therapeutic development, from early discovery to preclinical optimization. We offer comprehensive solutions that range from LNP Design for novel payloads to Process Optimization for established candidates, all backed by our advanced data science platform. Our core offerings include:
Customized, De Novo LNP Design
optimized for diverse payloads, including mRNA, siRNA, and lipophilic small molecules.
Precision Extrahepatic Targeting
achieved through custom surface functionalization with ligands, antibodies, or peptides to reach specific cell types (T-cells, DCs, cardiac fibroblasts) beyond passive liver uptake.
Systematic Lead Identification
powered by Machine Learning (ML) and multivariate analysis drastically reduces the trial-and-error R&D phase and speeds up candidate selection.
Controlled Adjuvanticity Engineering
to precisely manage the LNP's immune profile, ensuring superior efficacy while minimizing off-target inflammation and improving the safety margin.
End-to-End Formulation and Manufacturing
using scalable microfluidic technology, ensuring tight control over critical quality attributes (CQAs) for seamless transition to preclinical studies.
Comprehensive Analytical Package
including advanced CQA assessment, stability testing, and predictive in vivo efficacy modeling to bridge the IVIVC gap.
Four different LNP preparations were designed, and their components are all different. The same GFP-mRNA was transfected with them, and the transfection effect was observed under a fluorescence microscope to evaluate the transfection ability of LNP preparations.
Fig.2 The formulation and composition of some lipid nanoparticles with different components.2,3
Fig.3 The transfection effects of different lipid nanoparticles that transfected GFP-mRNA into different target cells.2,3
A: Yes. We specialize in extrahepatic targeting. Beyond liver-accumulating LNPs, our platform uses surface functionalization with targeting ligands (peptides, antibodies) to enable specific uptake in tissues like spleen, lung, or tumor microenvironment. Discuss your target organ with our team.
A: Absolutely. Our versatile framework optimizes Solid Lipid Nanoparticles (SLNs) and Nanostructured Lipid Carriers (NLCs) to enhance solubility, stability, and bioavailability of poorly performing lipophilic small molecules—this is a core competency.
A: LNP stability is prioritized. Final deliverables include comprehensive stability data, with systematic screening of stabilizing components (e.g., cholesterol, helper lipids) to optimize thermal and shelf stability, supporting informed storage/distribution decisions.
A: Generic LNPs are often liver-optimized for non-specific use. Our service delivers custom-engineered LNPs tailored to your payload's chemistry, target cell receptors, and desired immune response. Systematic design and predictive IVIVC reduce preclinical failure risk, supporting clinical success.
Creative Biolabs' Custom Lipid Nanoparticle Development Services offer systematic solutions for therapeutic delivery challenges. Combining advanced data science and formulation expertise, it ensures optimal stability, controlled immune response, and extrahepatic precision for payloads like mRNA, siRNA, and small molecules.
Contact Our Team for More Information and to Discuss Your Project| Cat. No | Product Name | Promoter |
|---|---|---|
| CAT#: GTVCR-WQ001MR | IVTScrip™ pT7-mRNA-EGFP Vector | T7 |
| CAT#: GTVCR-WQ002MR | IVTScrip™ pT7-VEE-mRNA-EGFP Vector | T7 |
| CAT#: GTVCR-WQ003MR | IVTScrip™ pT7-VEE-mRNA-FLuc Vector | T7 |
| CAT#: GTVCR-WQ87MR | IVTScrip™ pT7-VEE-mRNA-Anti-SELP, 42-89-glycoprotein Vector | T7 |
| Cat. No | Product Name | Type |
|---|---|---|
| CAT#: GTTS-WQ001MR) | IVTScrip™ mRNA-EGFP (Cap 1, 30 nt-poly(A)) | Reporter Gene |
| CAT#: GTTS-WK18036MR | IVTScrip™ mRNA-Human AIMP2, (Cap 1, Pseudo-UTP, 120 nt-poly(A)) | Enzyme mRNA |
| (CAT#: GTTS-WQ004MR) | IVTScrip™ mRNA-Fluc (Cap 1, 30 nt-poly(A)) | Reporter Gene |
| (CAT#: GTTS-WQ009MR) | IVTScrip™ mRNA-β gal (Cap 1, 30 nt-poly(A)) | Reporter Gene |
References
