The material at the heart of the study comes from the sponge Haliclona sp., whose skeleton is built from spicules—slender, needle-shaped rods of biosilica. In earlier work, the same group showed that intact spicules, massaged briefly into the skin, create dense fields of nanometer-scale microchannels that boost penetration of small drugs. Those channels, however, proved too narrow for biomacromolecules, which typically range from a few to hundreds of kilodaltons. The researchers’ new idea was to etch the spicules themselves, dissolving away the tip and, unexpectedly, the entire axial core to leave a continuous hollow channel running the length of each needle. This transformation converts each spicule from a solid puncturing pin into something closer to a microscopic drinking straw embedded in the skin.

Manufacturing the hollow structures required careful optimization of an alkaline etching process. The team immersed purified spicules in sodium hydroxide solutions of varying concentration and duration, then evaluated how many spicules developed open tips, how large the resulting channels were, and whether the etched structures retained the mechanical strength needed to pierce skin. The harshest condition tested—2 molar sodium hydroxide for 72 hours—produced the widest openings and highest opening rates but visibly degraded structural integrity. The sweet spot turned out to be 2 molar NaOH for 48 hours, which maximized hollow-channel formation while preserving the spicules’ ability to withstand handling and skin insertion. Scanning electron microscopy of cross-sections taken at the tip, mid-shaft, and base revealed a continuous internal lumen, and confocal microscopy after Nile Red staining confirmed that the channels readily admit fluid and dissolved compounds.

The etching pattern itself has an elegant biological explanation. Siliceous sponge spicules are built around a proteinaceous axial filament, and the alkaline treatment appears to preferentially dissolve along this central core, carving out the hollow channel along a pre-existing biological template. This means the manufacturing process exploits the sponge’s own architecture rather than fighting it—a rare example of a natural biomaterial being upgraded through a one-step chemical modification into something functionally analogous to an engineered hollow microneedle array, but without any of the cleanroom microfabrication that synthetic microneedles demand.

With the hollow spicules in hand, the researchers benchmarked them against a formidable lineup of competitors in Franz diffusion cell experiments using fresh porcine skin: intact spicules, conventional microneedle patches, dermaroller devices, iontophoresis, and plain subcutaneous injection. For sodium fluorescein, a small hydrophilic tracer, hollow spicules alone achieved total skin absorption of roughly 24 percent, rising to nearly 43 percent when paired with a 15-minute course of low-current iontophoresis. The combination produced a synergistic index of 1.44, meaning the two techniques together outperformed the sum of their individual effects. For larger fluorescent dextrans of 20, 40, and 150 kilodaltons, the gap widened dramatically. With the 20-kilodalton dextran, hollow spicules plus iontophoresis pushed absorption to about 35 percent with a synergistic index of 3.29, while intact spicules combined with iontophoresis showed no synergy at all—clear evidence that the hollow channels, not merely the puncture sites, were doing the heavy lifting.

Dose dependence and distribution uniformity emerged as two further advantages. When the team varied the amount of hollow spicules applied, penetration of the 150-kilodalton dextran scaled accordingly, giving clinicians a tunable knob for dosing. More striking was the spatial pattern: biomacromolecules delivered through spicule-treated skin spread evenly across the entire treated area, with no significant concentration differences among randomly sampled sites. Subcutaneous injection, by contrast, produced a hot spot at the needle entry point with essentially no detectable drug 5 millimeters or 1 centimeter away. For depot drugs, that pooling is sometimes desirable, but for vaccines and immunotherapies meant to engage skin-resident immune cells, uniform distribution could translate into more consistent uptake and fewer local adverse effects.

The platform’s most clinically resonant demonstration involved an antibody fragment. The team compared hollow spicules against laboratory-fabricated dissolving microneedle patches—10-by-10 arrays of quadrangular pyramidal needles, each about 820 micrometers tall and mechanically robust enough to withstand roughly 0.8 newtons of compressive force—for delivering a shark-derived anti-PD-L1 variable new antigen receptor, a model antibody-like therapeutic. The hollow spicules achieved total skin absorption of about 25 percent, roughly doubling the microneedle patch result of 11.5 percent and more than quadrupling the untreated control. Because antibody drugs represent one of the fastest-growing classes of biologics yet remain almost entirely injection-bound, a topical route that outperforms microneedles would be a meaningful advance for patients who self-administer these therapies.

To test whether the effect matters biologically, not just chemically, the researchers delivered ovalbumin, a classic model antigen, to guinea pigs over consecutive days and tracked immune activation. Both the injection group and the hollow-spicule group showed visible immune reactions by day 2, and by day 8 the spicule group’s responses, while milder than injection, remained significantly stronger than controls and intact-spicule groups. Blood analysis told the same quantitative story: ovalbumin-specific IgE levels were markedly elevated in the spicule group, and interleukin-4 concentrations showed no significant difference from the injection group. In other words, a topical massage of sponge-derived microneedles provoked an immune response functionally comparable to a needle in the flesh—a result with obvious implications for needle-free vaccination.

Safety data were encouraging but appropriately caveated. Mild redness and swelling after application resolved within 48 to 72 hours, and histological counts of immune cells in treated skin spiked to roughly 550 cells per analyzed region at 24 and 48 hours before falling back to baseline levels by day 10, statistically indistinguishable from untreated controls. Repeated application produced no chronic inflammatory infiltration, and examination of major organs revealed no abnormalities. The authors are candid, however, about a longer-term concern: silica is a recognized granulomatogenic material, and cutaneous silica granulomas can appear months or even years after exposure. Their 10-day observation window cannot rule out such delayed reactions, and the team calls for extended follow-up studies, including polarized-light assessment for birefringent particles, before the platform moves toward human use.

The study also contributes a quantitative framework for predicting how drugs will behave under spicule treatment. Because hollow spicules remain embedded in skin during use, they generate annular channels rather than the funnel-shaped perforations left by removable microneedles. Building on established microporous-skin permeability models, the researchers derived and fitted an equation capturing the dependence of permeability on molecular weight and oil-water partitioning across six test compounds, with the expected inverse relationship to molecular weight dominating the tested range. The team notes that validation in ex vivo human skin and clinical studies will be essential, since animal skin differs from human skin in barrier structure and immune responsiveness. Still, the combination of natural abundance, batch-to-batch dimensional consistency, low manufacturing cost, tunable dosing, uniform drug spread, and demonstrated vaccine-grade immune activation makes hollow sponge spicules one of the more compelling entries yet in the race to retire the hypodermic needle.

Subject of Research: Transdermal delivery of biomacromolecules using hollowed marine sponge spicules as natural microneedles

Article Title: Enhanced skin delivery of biomacromolecules using hollow sponge spicules

Article References: Mou, D., Yang, M., Jia, M., Liu, Y., Chen, J., Xiao, X., & Chen, M. (2026). Enhanced skin delivery of biomacromolecules using hollow sponge spicules. Bioengineering & Translational Medicine, 11(5), Article e70149. https://doi.org/10.1002/btm2.70149

Image Credits: AI Generated

DOI: 10.1002/btm2.70149

Keywords: drug delivery, microneedles, sponge spicules, transdermal, biomacromolecules, vaccination, biologics, iontophoresis, biosilica, skin barrier, antibody delivery, marine biotechnology