Hoda E. Mahmoud

There is a growing global interest in developing greener and safer pharmaceutical formulations that minimize environmental impact. In this study, we present a biotechnological nanoformulation combining prodigiosin (PG), a water-insoluble, microbially derived red pigment with multifunctional bioactivity and surfactin (SF), a lipopeptide biosurfactant known for its diverse surface-active properties. PG was produced by Serratia marcescens, spectrally characterized, and subsequently incorporated into preformed SF nanomicelles (nSF) via thermal sonication at 50 °C, yielding PG-loaded nanomicelles (nPG/SF). Physicochemical characterization of nPG/SF revealed spherical nanostructures with an average diameter of 227 ± 18.95 nm, a moderate polydispersity index (PDI) of 0.59 ± 0.17, a negative surface charge (-27.1 ± 0.97 mV), high entrapment efficiency (98%), and physical stability at 4 °C for at least 14 days. In terms of bioactivity, nanomicellization appeared to enhance the antibacterial effect of PG against Staphylococcus aureus and a clinical isolate of Pseudomonas aeruginosa, while significantly (p < 0.05) improving SF's cytotoxic activity against two breast cancer cell lines, MCF-7 and MDA-MB-231. Furthermore, using nSF as a carrier slightly increased PG’s anticancer activity, suggesting the potential for dose reduction of both PG and SF. Overall, this study provides a proof of concept for an eco-friendly, biosurfactant-based nanomicellar PG formulation with improved solubility, stability, and bioactivity, supporting its potential in pharmaceutical and biotechnological applications. Further investigations are warranted to validate and extend these findings.

Monascus red pigment (MRP) is a highly pigmented microbial secondary metabolite having a therapeutic potential, which can be further enhanced through incorporation into various drug carriers. In this study, MRP produced by Monascus purpureus ATCC16436 was microencapsulated using Saccharomyces cerevisiae ( S . cerevisiae ) ghosts (ScGs) as a biocarrier, resulting in an innovative bioformulation that integrates the properties of both components. Morphological analysis using light, electron, and confocal microscopy confirmed successful evacuation of S . cerevisiae cells, generating ScGs with a well-preserved three-dimensional structure. The ghosts showed a relatively large internal volume (~ 26 µm ³ ) surrounded by intact, negatively charged cell walls with distinct pores that facilitated the discharge of intracellular contents. Optimization of the microencapsulation process using a Box–Behnken experimental design (BBD) and response surface methodology (RSM) considering temperature, MRP concentration, shaking speed, and incubation time as independent variables, yielded an optimal formulation with a loading efficiency of 61.4 ± 2.3% at 25 °C, 300 mg/mL MRP, 125 rpm shaking rate, and 90 min incubation time. Digital, light, electron, and differential interference contrast (DIC) confocal microscopy confirmed dense MRP encapsulation, with uniform distribution of the pigment throughout the ScGs. The microencapsulated MRP demonstrated a biphasic sustained release profile in PBS (pH 7.4) containing 1.6% Tween 80. In terms of bioactivity, microencapsulation enhanced MRP cytotoxicity against the A549 lung cancer cell line (IC20 > 40, 10 and 3 µg/mL for ScGs, MRP and MRP-ScGs, respectively), consistent with increased cellular uptake observed via confocal microscopy. The MRP-ScGs represent a promising bio-microcapsule platform for biomedical applications, offering structural stability and enhanced therapeutic potential. Additionally, in silico bioinformatic analysis predicted multiple molecular targets associated with vital cellular functions, further supporting their potential in targeted drug delivery.

Lactobacillus acidophilus ghosts (LAGs) with the unique safety of a probiotic, inherent tropism for colon cells and multiple bioactivities offer great promise as drug carrier for colon targeting. We report herein on a novel bioinspired drug delivery system against colorectal cancer (CRC) cells based on LAGs functionalized with prodigiosin (PG), a proapoptotic bacterial metabolite. LAGs were prepared by a chemical method and highly purified by density gradient centrifugation. Multiple microscopic and staining techniques characterized LAGs by a relatively small size, size uniformity, a relatively large internal volume devoid of cytoplasmic and genetic materials and an intact negatively charged envelop. PG was highly bound to LAGs cell wall, generating a physiologically stable bioactive entity (PG-LAGs) active against HCT116 CRC cells at the cellular and molecular levels. Cell viability data underlined cytotoxicity of PG and LAGs and LAGs-induced enhancement of PG selectivity for HCT116 cells. Combination and Dose reduction indices anticipating dose reduction of PG and LAGs. Molecularly, PG-LAGs significantly modulated the expression of apoptosis-related biomarkers, caspase 3, P53 and BCL2, in favor of cytotoxicity against HCT116 cells relative to PG and 5-fluorouracil. Accordingly, LAGs offer promise as novel drug carrier for targeted colon delivery and PG-LAGs may bring therapeutic benefits in colorectal carcinoma.