Preparation and Characterization of Capsaicin Encapsulated Polymeric Micelles and Studies of Synergism with Nicotinic Acids as Potential Anticancer Nanomedicines.

Background/Objective/Methods: Capsaicin micelles were prepared by the direct dissolution using the amphiphilic copolymer Pluronic P123 and advanced for substantially novel submicro-nanocytotoxicity. Results: Superior cytotoxicity of capsaicin loaded nanomicelles vs. both the raw capsaicin and reference cisplatin in pancreatic PANC1, breast MCF7, colorectal resistant CACO2, skin A375, lung A549 and prostate PC3 cancer cell lines were delineated. Nicotinic acid (NA) derivative 39 (2-Amino IsoNA) had antiinflammatory potential but consistently lacked antiproliferation in MCF7, PANC1 and CACO2. Besides NA derivatives 8 (5-MethylNA) and 44 (6-AminoNA) exhibited lack of antiinflammation but had comparable antitumorigenesis potency to cisplatin in PANC1 cells. Though capsaicin loaded nanomicelles exerted pronounced antiinflammation (with IC50 value of 510 nM vs. Indomethacin's) in lipopolysacchride-induced inflammation of RAW247.6 macrophages; they lacked DPPH scavenging propensities. Free capsaicin proved more efficacious vs. its loaded nanocarriers to chemosensitize cytotoxicity of combinations with NAs 1(6-Hexyloxy Nicotinic Acid), 5(6-OctyloxyNA), 8(5-MethylNA), 12(6-Thien-2yl-NA), 13(5,6-DichloroNA) and 44(6-AminoNA) in CACO2, PANC1 and prostate PC3. Conclusion: Capsaicin loaded nanomicelles proved more efficacious vs. free capsaicin to chemo-sensitize antiproliferation of cotreatments with NA derivatives, 1, 5, 8, 12, 13 and 44 (in skin A375), 1, 5, 8 and 12 (in breast MCF7), and 1, 5, 12 and 44 (in lung A549).

Preparation and Characterization of Rutin-Encapsulated Polymeric Micelles and Studies of Synergism with Bioactive Benzoic Acids and Triazolofluoroquinolones as Anticancer Nanomedicines.

BACKGROUND: The study aimed to examine rutin micelles of advanced superlative dual cytotoxicity-antiinflammtion bioefficacies in substantially novel submicro-nanoaffinities vs. both the raw rutin and reference proapoptotic cisplatin. METHODOLOGY: Antiproliferative capabilities of rutin, benzoic acid (BA) and triazolofluoroqunolone (TFQ) derivatives were reported; hence chemosensitizing effects of rutin or its polymeric micelles (of improved solubility and bioavailability via direct dissolution using the amphiphilic copolymer Pluronic P123) in co-incubations with 5 BAs or 3 TFQ derivatives in a panel of 6 cancer cell lines were verified. RESULTS: Rutin loading in micelles was achieved with a loading efficiency of 59.5 ± 2.9%. The particle size of the micelles was found to be 18 ± 2 nm. Though Rutin loaded nanomicelles were of minimal DPPH radical scavenging activity; they had nitrogen oxide (NO) radical scavenging activity in lipopolysaccharide-induced RAW264.7 macrophages with equipotency to indomethacin (IC50 values (µM) 73.03 vs. 60.88; p=0.057). Remarkably nano-micelle formulation of rutin was proved of significantly more potent antineoplastic bioactivity with submicro-nanomolar affinities in the 6 cancer cell lines vs. both free rutin's and cisplatin's (except A549 lung cancer cell line). Rrutin nanomicelles chemo-sensitized all selected 8 cotreatments with BA derivatives and TFQs and, thus reducing the dose used against breast cancer MCF7 cells to submicro-nanomolar affinities of greater potencies than cisplatin's. Except for Triazolo-4-anisidine cipro butyl acid in PANC1, 2-Amino-3,5-Di iodo BA in A375 and 4-Nitrophenol in A549 incubations; rutin loaded nanomicelles chemosensitized 7/8 cotreating selected benzoic acid (BAs) derivatives and TFQs and chemosensitized pancreatic PANC1, skin A375 and lung A549 cancer cell lines, thus reducing the dose to submicro-nanomolar affinities of greater potencies than cisplatin's. Rutin loaded nanomicelles chemosensitize 6/8 cotreating selected benzoic acid (BA) derivatives and TFQs (except for 2-Amino-5-Bromo Benzoic Acid and Triazolo-4-anisidine cipro butyl acid), thus reducing the dose used against resistant CACO2 colorectal cancer cells.