Development of Pharmabiotic Gel-Serums with Lacticaseibacillus casei Postbiotics and Paraprobiotics Using Chitosan and Carbopol

Postbiotic and paraprobiotic preparations are increasingly investigated as non-viable microbial-derived components for topical formulation development, offering an alternative to systems containing live microorganisms. However, their physicochemical and biological performance may depend strongly on the polymeric carrier, and direct comparisons of postbiotic and paraprobiotic fractions derived from the same microbial source in different gel matrices remain limited. This study aimed to develop and comparatively evaluate Carbopol®- and chitosan-based pharmabiotic gel-serums containing Lacticaseibacillus casei-derived postbiotic (PB) and paraprobiotic (PPB) fractions. The formulations were characterized in terms of macroscopic appearance, pH, spreadability, and rheological behavior, and their antimicrobial activity, effects on preformed biofilm biomass, and DPPH radical-scavenging activity were evaluated. Blank Carbopol® and chitosan formulations and free PB and PPB fractions were included as controls to distinguish formulation-matrix-associated effects from those observed for the complete formulations. The developed gel-serums exhibited homogeneous initial macroscopic characteristics, pH values ranging from 4.22 to 5.66, and pseudoplastic shear-thinning behavior. Among the PB-containing systems, CA-CS-PB exhibited pronounced antimicrobial activity, with inhibition-zone diameters of 18.00 mm against Candida albicans and 19.93 mm against Candida krusei, and MIC values of 1156 μg/mL against both species. CA-CS-PB also reduced preformed Staphylococcus aureus and Pseudomonas aeruginosa biofilm biomass by 92.89% and 87.63%, respectively, and exhibited the highest DPPH radical-scavenging activity (73.50%). Among the PPB-containing systems, CA-C-PPB produced reductions of 94.63% and 93.71% in preformed S. aureus and P. aeruginosa biofilm biomass, respectively. Blank formulations also exhibited measurable biological responses, indicating that the activities of the complete formulations should be interpreted as formulation-level effects rather than being attributed exclusively to the incorporated PB or PPB fractions. Because PB and PPB were incorporated at different concentrations (5% and 1% w/w, respectively), these findings should not be interpreted as an equivalent-dose comparison of their intrinsic biological potency. Overall, the findings demonstrate the feasibility of incorporating L. casei-derived PB and PPB fractions into different polymeric gel-serum systems and highlight the influence of both the pharmabiotic fraction and carrier matrix on formulation performance. These results support further investigation of these systems as topical formulation platforms; however, storage stability, release behavior, compositional characterization, and skin-relevant safety and performance require further evaluation before dermocosmetic or dermatological applicability can be established.