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Pharmaceutical Services

Part 4: Inorganic Nanoparticles

Introduction:
Nanotechnology in the Pharmaceutical Industry

Part 4 of 4: Inorganic Nanoparticles

Drug-containing nanoparticles are often won or lost on how they’re made. In many cases, the formulation technique is as important as—if not more important than—the excipients themselves in determining particle size, stability, drug loading, and performance versus traditional dosage forms. Common approaches include (a) top-down size reduction (e.g., homogenization, nanomilling), (b) bottom-up assembly from solution (e.g., precipitation/nanoprecipitation, solvent evaporation), and (c) self-assembly via non-covalent interactions (e.g., microfluidics, dialysis).

Part 4: Inorganic Nanoparticles – Core Materials, Clinical Examples, and Emerging Theranostics

Inorganic nanotechnology is a wide-ranging category with applications across diagnostics, imaging, and materials science—and, more selectively, drug delivery. Unlike polymeric or lipid systems (where the nanoparticle is primarily a carrier), inorganic nanoparticles are often used when the core material itself provides unique physical functionality (e.g., magnetic or optical properties), or when a rigid inorganic matrix enables a specific release or tolerability profile.

Therapeutic use of inorganic nanoparticles can be powerful. However, it also demands careful material selection and safety justification, since many inorganic cores (especially heavy metals) raise additional toxicology and long-term fate questions. As Paracelsus famously observed, “the dose makes the poison”—and this is especially relevant here, because certain inorganic materials carry heightened neurotoxicity and/or carcinogenicity concerns if exposure is not tightly controlled. For that reason, inorganic nanoparticles are often treated as a last resort, and at Callan Pharma Services we generally recommend exploring polymeric or lipid-based approaches first.

This is Part 4 of our 4-part series, focused on inorganic nanoparticles—what they are, common design approaches, and how they’re used in real products and emerging technologies.

What Are Inorganic Nanoparticles?

Inorganic nanoparticles are engineered nanoscale particles built from inorganic materials such as metals, metal oxides, silica/ceramics, or semiconductors (e.g., quantum dots). They are typically stabilized with surface coatings (polymers, surfactants, or ligands) to control dispersion and biological interactions.

In pharma, inorganic nanoparticles appear in two main roles: (1) as carriers for more traditional delivery concepts, and (2) as functional materials where the inorganic core contributes directly to the therapeutic effect. While they are used more selectively than organic nanotechnologies, they can be justified in niche applications where unique physical properties outweigh the added development burden and risk.

Common Types of Inorganic Nanoparticles

1. Metal Nanoparticles

Metal nanoparticles are elemental metallic cores whose clinical value often comes from surface-area-driven reactivity or optical behavior. In medicine, many prominent uses are in devices, topical antimicrobial applications, and emerging “theranostic” concepts rather than classic systemic drug delivery.

Examples of metals:

  • Silver (Ag)
  • Gold (Au)

Pros:

  • Strong size-dependent surface activity (useful for antimicrobial surfaces/dressings)
  • Gold enables optical interactions (photothermal / imaging concepts) that are difficult to replicate with organic carriers

510(k) Example:

ACTICOAT™ FLEX: a wound dressing that incorporates nanocrystalline silver to provide a broad-spectrum antimicrobial barrier at the wound surface, helping reduce bioburden and infection risk during healing.

2. Metal Oxide Nanoparticles

Metal oxide nanoparticles are among the most clinically established inorganic nanomaterials, because certain oxides can be biocompatible (or biologically handled) and can provide useful magnetic or contrast properties.

Examples of metal oxides:

  • Iron oxide (superparamagnetic iron oxide (SPIO) & ultra-small superparamagnetic iron oxide (USPIO))
  • Emerging examples include cerium oxide, zinc oxide, titanium dioxide

Pros:

  • Can provide intrinsic physical functionality (e.g., superparamagnetism for imaging)
  • With the right coating, can achieve stable colloids and controlled in vivo handling

Drug Product Example:

  • FERAHEME® (ferumoxytol): an FDA-approved IV iron replacement therapy composed of a superparamagnetic iron oxide core coated with polyglucose sorbitol carboxymethylether, with an overall colloidal particle size of ~17–31 nm. While not approved as an MRI contrast agent, ferumoxytol is used off-label at some centers for MRI due to its superparamagnetic properties.

3. Ceramic / Silica-Based Nanoparticles

Ceramic nanoparticles (especially silica-based materials) are attractive because they can be engineered to have tunable surface chemistry and, in some architectures, can act as porous matrices or shells that modulate local exposure and tolerability.

Examples of ceramic / silica materials:

  • Silicon dioxide (silica; including shell/microcapsule architectures)
  • Emerging examples include calcium phosphate, alumina (Al2O3), and titania (TiO2)

Pros:

  • Tunable surface chemistry (charge, hydrophilicity, and ligand attachment)
  • Can be used as a barrier/shell to reduce local irritation and enable controlled release of irritating actives

Drug Product Example:

EPSOLAY® (benzoyl peroxide) cream: uses a microencapsulation approach in which benzoyl peroxide is housed within silica-based microcapsules, creating a physical barrier between the active and the skin surface. This helps improve tolerability (e.g., less irritation) while enabling a more controlled release of benzoyl peroxide over time at the application site.

4. Quantum Dots

Quantum dots are nanoscale semiconductors with distinctive photoluminescence. In pharma/biomedicine they are most often explored for imaging and specialized applications where their optical behavior is a core part of the mechanism.

Examples:

  • Cadmium selenide (CdSe)–based quantum dots
  • Indium phosphide (InP)–based quantum dots (cadmium-free alternative for bioimaging / biomedical exploration)

Pros:

  • Unique optical behavior (photoluminescence) enabling imaging/photonic applications that are hard to match with organic carriers
  • Size-tunable, narrow emission (and broad excitation) — supports multiplexed imaging and cleaner spectral separation than many organic dyes

Clinical-Stage Example:

  • 2C Tech’s 2C-QD Quantum Dots (CdSe 655): Clinical success has been limited, but 2C Tech’s 2C-QD keeps quantum dots on the ophthalmology radar by positioning them as “miniature light converters” that shift incoming light to better stimulate retinal cells. In early clinical exploration, the company evaluated an intravitreal cadmium/selenium (CdSe) ~655 nm quantum dot for retinitis pigmentosa (RP), a genetic disease marked by progressive photoreceptor degeneration.

Key Advantages of Inorganic Nanoparticles

Across these different subclasses, inorganic nanoparticles can offer:

  • Access to functions organic carriers can’t easily replicate (magnetic, high electron density for contrast, optical/photothermal behavior).
  • Structural rigidity and stability, which can be useful for surface functionalization, shell/barrier designs, and certain controlled-exposure concepts.
  • Theranostic potential: the same particle can support diagnostics + therapy, enabling imaging-guided dosing, patient selection, or response monitoring.
  • Formulation “toolbox expansion” for niche cases where polymers/lipids underperform—particularly when the inorganic material is part of the mechanism, not just a passive carrier.

Formulation Design Considerations & Challenges

Designing an inorganic nanoparticle drug product usually succeeds or fails on surface chemistry, colloidal stability, analytics, and long-term fate:

Material selection and safety justification

  • Choose cores/coatings with the strongest available clinical/regulatory precedent (or be prepared for heavier nonclinical packages).
  • Address elemental impurities, leachables, and long-term tissue fate early—especially for heavy metals or non-biodegradable cores.

Surface coating, stability, and biodistribution

  • Surface coatings often determine whether the system is viable (aggregation control, protein corona behavior, macrophage uptake, circulation time).
  • Balance charge (stability) vs tolerability (irritation, complement, opsonization) and route-specific constraints (IV vs topical vs intravitreal).

Manufacturing and sterilization strategy

  • Process selection matters (top-down vs bottom-up vs self-assembly) because it changes particle size distribution, surface defects, and reproducibility.
  • Sterilization can be non-trivial (filtration feasibility, heat sensitivity of coatings, particle robustness).

Analytics and control strategy

  • Expect a multi-method characterization package: size/PDI (e.g., DLS/NTA), morphology (TEM/SEM), surface charge, coating integrity, free vs bound species, and elemental analysis (e.g., ICP-MS) where relevant.
  • Tight control of particulates/specs is essential for injectables (and often ocular products).

Emerging Technology Spotlight: Theranostic Gadolinium-Based Nanoparticles (AGuIX®)

One of the clearest “next wave” opportunities for inorganic nanoparticles is theranostics—particles designed to combine imaging + therapy in a single platform.

What it is

  • AGuIX® nanoparticles are reported as ultra-small (sub-5 nm) polysiloxane-based particles bearing gadolinium chelates, developed for MRI visibility and radiosensitization concepts.

Why it’s interesting

  • The gadolinium component supports MRI contrast, enabling visualization of distribution and tumor localization.
  • The platform has been evaluated in clinical contexts alongside radiotherapy (e.g., brain metastases / glioma-oriented programs are described in the literature and trial records).

What it means for sponsors

  • AGuIX® is a good example of where inorganic nanoparticles can truly differentiate—not by improving solubility, but by adding a measurable function (imaging) that can be paired with therapy. For development teams, the value proposition shifts toward image-guided dosing, patient selection, and response monitoring, where the nanoparticle’s physical behavior is part of the mechanism and part of the clinical story.