Data Interpretation Paradoxes in a Nanoencapsulated α-Mangostin Hydrogel Film for Anti-Acne Therapy [Response to Letter]

Dear editor

We sincerely thank the correspondent for their valuable comments regarding our published paper “Nanoencapsulated α-Mangostin Loaded Chitosan-Alginate Hydrogel Films for Enhanced Topical Anti Acne Therapy”.1,2

On their first point, the values reported in Table 5 represent bacterial loads expressed as CFU/g rather than the raw colony numbers observed on the agar plates. Accordingly, the apparent values below 30 in Table 5 should not be interpreted as plate colony counts. The observed reductions in bacterial burden were further supported by the corresponding histopathological findings and improvement in inflammatory parameters, which together corroborate the antibacterial efficacy of the formulations.

On their second point, we appreciate the correspondent’s careful evaluation regarding the interpretation of the polydispersity index (PDI). We acknowledge that our original statement, namely that a moderate PDI (<0.5) indicates a relatively homogeneous size distribution supporting formulation stability and uniform drug release, may have been overly general in the context of the DLS analysis. In the present formulation, the measured PDI of 0.450 is more appropriately interpreted as reflecting a moderately polydisperse particle size distribution. The polydispersity index (PDI) should not be interpreted as a standalone indicator because nanoparticle quality and stability are determined by multiple physicochemical parameters rather than particle size distribution alone. Therefore, PDI values obtained by dynamic light scattering (DLS) should be interpreted together with other complementary physicochemical characteristics to provide a more comprehensive assessment of nanoparticle systems.3,4

Despite a PDI value of 0.450, our formulation exhibited a high positive zeta potential (+40.9 ± 1.91 mV), which is generally considered indicative of good electrostatic stability. Furthermore, the nanoparticles exhibited high encapsulation efficiency, sustained α-mangostin release, preserved film integrity, and significantly improved antibacterial and anti-inflammatory performance. Therefore, the formulation remained physically and functionally stable, despite exhibiting a moderately broad particle size distribution.

On their third point, we respectfully clarify that our intention was to describe the electrostatic association between chitosan and sodium alginate rather than imply the presence of a perfectly continuous alginate shell. The nanoparticles were prepared by sequential ionic gelation, in which chitosan was first crosslinked with sodium tripolyphosphate (TPP) and subsequently allowed to interact electrostatically with sodium alginate. Under these conditions, the final surface charge is governed by the polymer stoichiometry, degree of chitosan protonation, and extent to which amino groups remain exposed at the particle surface. Accordingly, the positive zeta potential observed (+40.9 mV) does not necessarily indicate the absence of alginate incorporation; rather, it suggests that a fraction of the protonated amino groups of chitosan remained accessible at the slipping plane, likely because chitosan was present in excess relative to alginate. FTIR analysis further revealed characteristic spectral changes consistent with electrostatic interactions between the protonated amino groups of chitosan and the carboxylate groups of alginate, supporting the formation of a chitosan-alginate polyelectrolyte complex rather than a fully coated core–shell structure. Therefore, the zeta potential alone cannot be used as definitive evidence for the presence or absence of alginate incorporation. Similar behavior has been reported for chitosan-alginate polyelectrolyte complexes, whose surface charge is strongly influenced by the polymer ratio and preparation conditions.5,6

Disclosure

The authors declare no conflicts of interest in this communication.