Search

Designing efficient drug delivery systems for optimum therapeutic outcomes and minimum adverse effects remains a pivotal focus in pharmaceutical research. Understanding the nature of interactions between drugs and drug carriers and the drug-release mechanism are the key aspects for the development of effective delivery systems. This work presents a detailed investigation into the intricate interactions between niosomes and the drug Phenosafranin (PSF), and the subsequent release induced by a variety of cyclodextrins (CDs) employing a multifaceted approach. Ensemble average spectroscopic and single molecular level investigations based on fluorescence correlation spectroscopy (FCS), are employed to explore the binding interactions of PSF with the niosome membrane. Subsequently, the release of the drug was studied by disrupting the niosome structure using various CDs, and their efficacy was accessed through steady-state and time-resolved photophysical responses. FCS experiments provided precise insights into the binding and drug release process at the single-molecule level through the variation in translational and diffusion characteristics of the drug. Additionally, isothermal titration calorimetric (ITC) investigations further revealed the thermodynamics governing the CD-niosome host:guest interactions and the varying potential of different CDs in disrupting the niosome to release the drug which were further validated by electron microscopy and confocal fluorescence microscopy analyses. A broader analysis of niosomes prepared with various nonionic surfactants highlighted the influence of cavitand size and structure on the interaction with different niosome constituents. This comprehensive analysis sheds light on the complex interplay of these components and their interactions, providing insights into drug delivery systems and their potential therapeutic applications.

Basal Cell Carcinoma (BCC) and Actinic Keratosis (AK) are prevalent skin conditions with significant health complications. The molecular mechanisms underlying these conditions and their potential shared pathways remain ambiguous despite their prevalence. Therefore, this study aims to elucidate the common molecular pathways and potential therapeutic targets for BCC and AK through comprehensive computational network analysis. Linkage analysis was performed to identify common liable genes between BCC and AK. Protein-protein interactions (PPIs), Topological properties, GO enrichment, pathway enrichment, and gene regulatory network analyses were also performed to reveal potential molecular mechanisms and pathways. Furthermore, we evaluated protein-drug interactions (PDIs) to identify potential therapeutic targets. Our analysis revealed 22 common genes between BCC and AK: TP53 , EGFR , CDKN2A , MMP9 , PTGS2 , VDR , BCL2 , MMP2 , EZH2 , TP63 , FOXP3 , MSH2 , MMP14 , FLG , MC1R , CDKN2B , TIMP3 , TYR , SOX10 , IRF4 , KRT17 , and NID1 . PPI network analysis highlighted TP53 and EGFR as central hubs, validated using RNA-seq data. Co-expression and physical interaction analysis revealed a strong interplay between the common genes at the transcriptional and functional levels. GO analysis identified skin cancer-relevant terms: "skin development", "immune system development", and "response to radiation" as significantly enriched biological processes, while pathway enrichment analysis highlighted several cancer-related pathways enrichment. Gene regulatory network analysis revealed complex interactions between genes, miRNAs, and transcription factors, with TP53 , BCL2 , and EGFR playing central roles. PDI network analysis identified ibuprofen as a potential therapeutic agent targeting PTGS2 and BCL2, while other proteins VDR, MMP2, MMP9, and TYR showed interactions with multiple drugs. This computational analysis provides valuable insights into the shared molecular mechanisms of BCC and AK, revealing common pathways and potential therapeutic targets for developing novel treatment strategies and repurposing existing drugs for these prevalent skin cancers. Therefore, these findings may guide future research in understanding and developing targeted therapies for both conditions., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2025 The Authors.)