Stratum Corneum Deposition Mechanics at the Nano-Scale: How Carrier Size Shapes Delivery Pathway

The relationship between nanoparticle diameter and stratum corneum deposition pathway – and how the NanoBase™ tri-domain Architecture is designed around three domains rather than a single carrier.

DOI Reference: 10.5281/zenodo.18616576

The Stratum Corneum as a Nano-Scale Selective Barrier

The stratum corneum (SC) is a 10-20 μm barrier comprising 15-25 layers of terminally differentiated corneocytes embedded in a structured lipid matrix. This “brick and mortar” architecture creates three distinct surface transport pathways: intercellular (between corneocytes through lipid lamellae), transcellular (through corneocytes), and appendageal (via hair follicles and sweat glands). At the macro-scale, conventional formulations rely primarily on passive diffusion governed by Fick’s law, with surface uptake determined by partition coefficient and molecular weight. At the nano-scale, the literature proposes that carrier diameter strongly influences which pathway dominates.

Size frameworks in the skin literature generally propose that particles above 500 nm stay on the skin surface, that between 200-500 nm carrier-skin interaction occurs mainly through appendageal structures (follicles and furrows), and that below 200 nm closer interaction with the intercellular lipids becomes possible; results vary by carrier and test method. NanoBase™ is engineered to a ~185 nm design target (DLS-characterised every batch, DOI: 10.5281/zenodo.18616576); that size is a formulation-design parameter, and NanoBase™ makes no deposition or penetration claim of its own.

Intercellular Lipid Channel Architecture and Carrier Compatibility

SC intercellular channels are organized as repeating lipid bilayers composed primarily of ceramides (ceramide NP, ceramide AP, ceramide EOS), cholesterol, and free fatty acids (predominantly lignoceric acid, C24:0). These lamellae maintain a characteristic repeat distance of approximately 13 nm (long periodicity phase) and 6 nm (short periodicity phase). For a nanoparticle to engage this matrix, it must either occupy the aqueous domains between lamellae or transiently interact with the lipid organization at the surface.

NanoBase™ is designed with this architecture in mind. The nanocolloidal domain hosts lipophilic actives, the nanoliposomal domain (phospholipid bilayer vesicles) hosts amphiphilic actives, and the nanomicellar domain hosts water-soluble actives.

Why Single-Carrier Systems Fail at Multi-Active Delivery

Single-carrier nano systems employ one carrier type - typically either a nanoemulsion or a liposomal system. This forces all actives, regardless of their physicochemical properties (log P, molecular weight, charge state), through one carrier environment. A hydrophilic peptide (e.g., palmitoyl tripeptide-1, MW ~623 Da, water-soluble) loaded into a nanoemulsion will exhibit poor encapsulation efficiency and rapid premature release before reaching the intended surface target. Conversely, a lipophilic active (e.g., retinol, log P ~6.3) loaded into a nanomicellar system will partition out of the hydrophilic core and accumulate at the carrier surface.

The NanoBase™ tri-domain architecture is designed to address this incompatibility by giving each active ingredient a carrier domain suited to its physicochemical profile: lipophilic actives (log P > 3) to the nanocolloidal domain, amphiphilic actives to the nanoliposomal domain, and hydrophilic actives (log P < 1) to the nanomicellar domain. Each active sits in a domain suited to it, designed to limit cross-domain interference (design specification).

Functional Category and Target Skin Layer

Different active categories behave differently in a formula, and carrier domain assignment should reflect their chemistry rather than treating all actives identically. Peptides (e.g., palmitoyl tripeptide-1, copper peptides) need protection from hydrolysis in the formula. Antioxidants need protection from oxidation. Hydrating and humectant actives need to stay evenly distributed for a consistent hydrating feel. NanoBase™ is designed so that each functional category can be placed in the domain best matched to its chemistry, rather than forcing every active into one carrier environment.

Temperature and Hydration Effects on Nano-Scale Deposition

SC barrier function is not static. Skin temperature (typically 32°C at the surface) increases lipid fluidity in the intercellular matrix, widening effective channel dimensions. Occlusion or high ambient humidity increases SC hydration, swelling corneocytes and expanding intercellular spaces. Both conditions are reported to affect nano-scale deposition in the literature, so any deposition testing of a finished formula should specify occluded and non-occluded conditions at controlled temperature (32 ± 1°C).

For brand partners developing product claims, deposition data belongs to the finished formula: test protocols should simulate actual use conditions (post-cleansing skin temperature, typical ambient humidity, and realistic application thickness). NanoBase™ itself makes no deposition claim; the brand substantiates its finished formula’s claims.

Implications for Formulation Design

Understanding SC mechanics at the nano-scale reduces the guesswork in formula design. Rather than optimizing a single carrier, the NanoBase™ tri-domain Architecture assigns each active to a domain matched to its physicochemical profile. The Architecture is DLS-characterised every batch and documented in a published technical preprint (DOI: 10.5281/zenodo.18616576); the finished formula built on it is the delivery system.