SAXS for Drug Delivery Systems

Nanoscale structural characterization of liposomes, lipid nanoparticles (LNPs), nanoemulsions, and advanced delivery carriers using small‑angle X‑ray scattering.

Lipid‑Based Nanoparticles Evaluated with SAXS

For various drug delivery systems — such as liposomes, nanoemulsions, solid lipid nanoparticles, and nanostructured lipid carriers — SAXS (Small‑Angle X‑ray Scattering) is a valuable tool to reconstruct the nanoscale structure of the carrier, either in its unloaded form or when loaded with a drug.

The structural information obtained can include the type of lipid phase (e.g., lamellar, hexagonal, or disordered), periodicity, electron density distribution, and the spatial arrangement of different components within the nanoparticle.

Understanding how these structural properties depend on factors such as temperature, pH, and concentration is crucial for optimizing and designing effective drug delivery carriers.

SAXS Applications for Drug Delivery

Liposomal Formulations

Characterization of lipid bilayer thickness and density, PEG corona dimensions, and nanocrystalline drug loading within liposomes.

Lipid Nanoparticles (LNPs)

Structural analysis of mRNA‑LNP assemblies, lipid organization, and particle morphology for gene therapy and vaccine applications.

Micelle Structure

Determination of micelle size, shape, and internal structure for surfactant‑based delivery systems.

Nanoemulsions

Size distribution and interfacial properties of oil‑in‑water and water‑in‑oil nanoemulsions.

Solid Lipid Nanoparticles

Crystalline structure of lipid matrix and drug distribution within solid lipid nanoparticles (SLN).

Nanostructured Lipid Carriers

Mixed lipid phase characterization and drug encapsulation efficiency in NLC systems.

mRNA & siRNA Lipid Nanoparticle Characterization

SAXS provides critical structural insights for nucleic acid-loaded lipid nanoparticles used in mRNA vaccines, siRNA therapeutics, and gene therapy applications.

From early formulation development through cGMP batch release, SAXS reveals the internal organization that determines delivery efficiency and stability.

Ionizable Lipid Systems

Characterization of LNPs containing ionizable lipids (SM-102, ALC-0315, MC3/DLin-MC3-DMA) — the key components enabling endosomal escape and cytoplasmic delivery.

mRNA Encapsulation

Structural analysis of mRNA organization within the LNP core, lipid phase behavior, and electron density distribution affecting payload protection.

siRNA-LNP Assemblies

Characterization of siRNA lipid nanoparticles for RNAi therapeutics, including those similar to approved products like Onpattro (patisiran).

Multilamellar LNPs (MLNPs)

Analysis of multi-layered lipid nanoparticles offering enhanced payload capacity and sustained release profiles for nucleic acid delivery.

Key Parameters for mRNA/siRNA-LNP Development

Lipid Phase

Lamellar, hexagonal, or disordered organization

Core Structure

Electron density profiles and RNA localization

Size & PDI

Particle distribution for regulatory compliance

Thermal Stability

Structure under storage and stress conditions

Oncology Drug Delivery Applications

Lipid nanoparticles and liposomes are at the forefront of cancer therapeutics — from established chemotherapy reformulations to next-generation mRNA cancer vaccines and targeted delivery systems.

mRNA Cancer Vaccines

Structural characterization of personalized neoantigen vaccines and cancer immunotherapy formulations delivered via LNPs.

Liposomal Chemotherapy

SAXS analysis for Doxil-like pegylated liposomal formulations, encapsulation verification, and bilayer characterization.

Targeted Delivery Systems

Characterization of actively-targeted LNPs with surface ligands for tumor-specific accumulation and EPR-optimized particle sizes.

Combination Therapy Carriers

Multi-drug co-loaded nanoparticles for synergistic cancer treatment — structural analysis of multi-component systems.

Stimuli-Responsive LNPs

pH-sensitive, temperature-responsive, and enzyme-triggered delivery systems for tumor microenvironment-activated release.

In Vivo Gene Therapy

LNP carriers for CAR-T mRNA delivery and CRISPR-based oncology applications requiring precise structural control.

Aerosols for Lung & Nasal Delivery Routes

The lung and nasal delivery routes are commonly used for aerosols. This is a promising delivery route, yet accurate and repeatable dosing remains a technological challenge.

Once a pressurized dose of an aerosol is delivered to the sampling surface, the most important factors to control using XRPD are:

  • Polymorphic content of the API
  • Quantity of the API within one dose
  • Dose repeatability

Drug carriers (i.e., microspheres, liposomes, nanoparticles) may be assessed using SAXS and complementary methods when entering the fluid phase.

Ophthalmic & Otic Delivery Routes

The characterization of liquid formulations is similar to that used for the characterization of drugs with an injection delivery route, and are performed using the SAXS methodology.

Characterization of liquid‑crystal‑based formulations is performed using a combination of SAXS and XRPD techniques.

Liquid Formulations

SAXS characterization of nanoparticles, vesicles, and colloidal structures in ophthalmic and otic solutions.

Liquid‑Crystal Systems

Combined SAXS/XRPD analysis of lyotropic liquid crystals for controlled release applications.

In‑Situ Gel Systems

Structural transitions and gel formation monitoring under physiological conditions.

Transdermal Delivery Route

For transdermal delivery systems including patches and topical formulations, XRPD provides critical information about API solid state and distribution within matrices.

Learn more about transdermal patch characterization →

Key Structural Parameters

SAXS analysis of drug delivery systems provides quantitative structural parameters:

Lipid Phase Type

Identification of lamellar, hexagonal, cubic, or disordered lipid phases.

Bilayer Dimensions

Thickness, repeat spacing, and electron density profiles of lipid bilayers.

Particle Size & Shape

Radius of gyration (Rg), particle size distribution, and morphology determination.

PEGylation

Characterization of PEG corona thickness and density in stealth liposomes.

Drug Loading

Detection and localization of crystalline or amorphous drug within carriers.

Temperature Dependence

Phase transitions and structural stability as a function of temperature, pH, and ionic strength.

DANNALAB Capabilities

cGMP SAXS Testing

cGMP‑compliant SAXS characterization with 21 CFR Part 11 traceable data and QA‑approved deliverables.

Method Development

Collaborative development of fit‑for‑purpose SAXS methods for novel delivery systems.

Temperature Control

In‑situ SAXS with precise temperature control for phase transition and stability studies.

Model Fitting

Advanced modeling including core‑shell, bilayer, and multi‑component systems.

Small Sample Volumes

Analysis possible with minimal sample quantities in native formulation buffers.

Combined SAXS/XRPD

Integrated characterization using both techniques for comprehensive structural understanding.

Regulatory & Development Support

DANNALAB provides SAXS characterization data suitable for regulatory submissions across multiple pathways — from IND-enabling studies through commercial batch release.

505(b)(2) Applications

Structural characterization supporting new formulations of approved drugs, including LNP-based reformulations of existing therapeutics.

IND-Enabling Studies

CMC characterization data packages for Investigational New Drug applications with cGMP-compliant documentation.

Batch Release Testing

Routine SAXS testing for manufacturing consistency and critical quality attribute verification.

Comparability Studies

Structural comparison between batches, manufacturing sites, or process changes to demonstrate product consistency.

SAXS Method Information

Detailed technical information about our SAXS methods and capabilities.

Learn more about SAXS →

Nanoparticles

Characterization of inorganic and organic nanoparticles for pharmaceutical applications.

Nanoparticle services →

Biopharmaceuticals

SAXS for proteins, peptides, and biologics in native environments.

Biologics services →

Discuss Your Drug Delivery Project

Contact our technical team to discuss your drug delivery system characterization needs, request a quote, or get expert advice on SAXS method development.

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