Abstract
Despite recent advances in the treatment of human colon cancer, the chemotherapeutic efficacy against colon cancer is still unsatisfactory. The complexity in colorectal cancer treatment leads to new research in combination therapy to overcome multidrug resistance in cancer and increase apoptosis. The objective of the present research work was to develop polyplexes for co-delivery of plasmid DNA with retinoic acid against colorectal cancer cell line (HCT-15). Plain polyplexes were prepared using chitosan and hyaluronic acid solution (0.1% w/v), whereas retinoic acid polyplexes were prepared using ethanol: water (1:9 v/v) system. The particle size was observed in the order of chitosan solution > blank polyplex > retinoic acid-loaded polyplex. Encapsulation efficiency of retinoic acid was found to be 81.51 ± 4.33% for retinoic acid-loaded polyplex formulation. The drug release was observed to be in a controlled pattern with 72.23 ± 1.32% release of retenoic acid from polyplex formulation. Cell line studies of the formulation displayed better cell inhibition and low cytotoxicity for the retinoic acid-loaded polyplexes in comparison to pure retinoic acid, thus demonstrating better potential action against colorectal cancer cell line HCT-15. Retinoic acid-loaded polyplexes indicated higher potential for the delivery of the active whereas the cell line studies displayed the efficacy of the formulation against colorectal cancer cell line HCT-15.
Highlights
According to the latest statistical studies, colorectal cancer (CRC) stands third most common cancer worldwide after blood and lung cancers [1]
CS solution of equal volume was added to sodium sulphate solution; the solution was vortexed for 30 s and submerged in an ice bath to maintain the temperature at 5 °C. 0.1% w/v hyaluronic acid (HA) solution was added to 5 mM sodium sulphate and CS mixture
On the basis of evaluations tests like particle size, % EE and in vitro drug release, formulation P3 without retinoic acid and formulation P4 containing retinoic acid, CS, HA, sodium sulphate and DNA were found to be suitable against CRC cell line HCT-15
Summary
According to the latest statistical studies, colorectal cancer (CRC) stands third most common cancer worldwide after blood and lung cancers [1]. Recent trends in nanomedicine include the use of combined therapy of cytotoxic drugs loaded with nanocarriers to offer prolonged release, sitespecific delivery and reduction or elimination of first-pass metabolism. Polymer-based nanoparticulate systems like polymer nanocapsules, polymeric mesoporous nanoparticles, nanogels, polyplexes, polymer-lipid hybrid nanosystems, polymer-drug/protein complex, polymeric dendrimers, etc. The combined therapy includes DNA or RNA to assemble the nanoparticles for the expression or knockdown of genes to enhance the effectiveness of cytotoxic drugs like cisplatin, doxorubicin, etc. Cationic polymers such as chitosan (CS), poly(allylamine hydrochloride), polyethylenimine, etc. CRC demonstrated the presence of high levels of protein in the intestinal tissues and expressed poor degradation of retinoic acid in comparison to healthy individual. Using externally supplemented retinoic acid in the intestine or blocking the enzyme degradation significantly reduce the burden of cancer growth in the patients [10]
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