A recent increase in the use of biomolecules as carrier systems has led to the development of biomolecule-based nanoparticles (NPs) for the treatment of cancer. In a recent article in the journal Materials Today Communications, the authors developed polymeric NPs of polycaprolactone (PCL) and polyhydroxybutyrate (PHB) decorated with hyaluronic acid (HA) encapsulated with encorafenib (ECF) to treat colorectal cancer. They hypothesized that synthesized NPs reduced reactive oxygen species (ROS) by cell internalization and subsequent apoptotic arrest.
Study: Development and characterization of surface scaffolds of hyaluronic acid with polymeric nanoparticles loaded with Encorafenib for the targeting of colorectal cancer. Image credit: Kateryna Kon / Shutterstock.com
Polymers in drug delivery
Targeting site-specific drugs improves the bioavailability of a drug at a target receptor site, and the conjugation of drug molecules with polymer macromolecules could serve the purpose. To this end, the limited background reported the combination of HA with PCL and PHB, suggesting that the manufacture of these polymer-based therapeutic agents may protect the drug molecules from any enzymatic or chemical degradation, thereby improving the its physicochemical stability. Nanoformulation involving these polymer-based therapeutic agents could be potential carrier systems in the treatment of cancer to improve the specificity of the target in drug release and the consequent cell absorption.
The exceptional solubility and biocompatibility of PCL are suitable properties for drug encapsulation. Due to its degradation by microbial esterase and lipase, PCL could be used for the encapsulation of colon-specific drugs. In addition, surface modification of NPs with ligands and PCLs can improve drug delivery to cells. The hydrophobicity of PCL is advantageous for the transport of hydrophobic chemotherapeutics such as class II and IV drugs of the biopharmaceutical classification system (BCS). Thus, by encapsulating a BSC class II drug, ECF could improve its delivery and bioavailability to the target site. PHB is a biological polyester found in eukaryotic and bacterial cells. The combination of PHB with 5-fluorouracil and cellulose acetate phthalate may facilitate the treatment of colorectal cancer.
HA, a natural mucopolysaccharide, has properties such as non-immunogenicity, biocompatibility, chemical versatility, biodegradability, and non-toxicity. In addition, because HA is an unsulfated glycosaminoglycan, it has a strong affinity for colon cancer cells that overexpress CD44. N-acetyl-d-glucosamine and d-glucuronic acid are the two components of HA that interact with overexpressed CDD4 cancer cells.
ECF-loaded polymeric NPs
In the present study, researchers formulated ECF-PHB-NPs, ECF-PCL-NPs, HA-ECF-PCL-NPs, and HA-ECF-PHB-NPs to minimize drug demand and improve bioavailability. The prepared polymeric NPs were characterized by their morphology, zeta potential, in vitro drug release profile, biocompatibility, pharmacokinetic profiles, and histopathology. The aim of the preparation of said polymeric NPs was to improve their cell absorption by down-regulating colorectal cancer cells overexpressing CD44. In addition, HCT116 colorectal cancer cell lines were used for in vitro cancer and genotoxicity studies.
Research results
Scanning electron microscope (SEM) images showed that ECF-loaded polymeric NPs had a particle size of less than 200 nanometers and a polarity dispersion index (PDI) of less than 0.3. The zeta potential and particle size of HA-ECF-PHB-PHB NPs confirmed that the conjugation of ECF-loaded polymeric NPs with HA increased the size of NPs particles due to the nature of HA mucopolysaccharides. . Similarly, PHB-conjugated ECF-loaded polymeric NPs showed a larger particle size (162.32 ± 4.52 nanometers) than PCL-conjugated counterparts (157.56 ± 6.78 nanometers) due to the physical flexibility of PCL.
Due to the presence of N-acetyl-D-glucosamine copolymer and D-glucuronic acid in HA, the researchers observed the high anionic nature of HA-ECF polymeric NPs, i.e. -32.67 ± 3.34 millivolts for HA-ECF-PCL-NPs and 33.37 ± 3.78 millivolts for HA-ECF-PHB-NP, respectively. These copolymers increase the molecular weight and negative zeta potential of NPs. In addition, due to the presence of polyester diols and free radical PVA on the surface of the NPs, the PCL-ECF polymeric NPs showed a negative zeta potential of -15, 78 ± 4, 01 millivolts.
The researchers observed that the nature of the polymer had a significant impact on the efficiency of drug entrapment and loading. The molecular mass of the polymer significantly affected performance, drug loading capacity, and trapping efficiency. The higher molecular weight of HA (3×106 grams per mole) provided stiffness to NPs, allowing high efficiency of drug entrapment and loading in HA-ECF-PCL-NPs and HA-ECF-PHB-NPs. Due to the electrostatic interaction between polymers and ECF, the latter showed the maximum adsorption on the surface of the polymers.
The ECF Fourier Transform (FTIR) spectra showed characteristic peaks at 3399.84 and 1629.25 inverse centimeters that corroborate the presence of amides (RCONH2) and the corresponding amine deflection (NH). . The PCL FTIR spectrum showed a peak hydroxyl (-OH) dimer at 3334.37 centimeters inverse and an olefinic stretch (C = C) at 1669.92 centimeters inverse. PBL showed a characteristic inverse peak of 1752.74 centimeters, indicating the presence of unconjugated ester.
Conclusion
In conclusion, the team manufactured HA-coated polymeric ECF NPs (HA-ECF-PHB-NPs and HA-ECF-PCL-NPs) to treat colorectal cancer. Due to favorable properties such as proper particle size, entrapment efficiency, sustained release of ECF, biocompatibility, and excellent pharmacokinetic profile, HA-ECF-PHB-NPs were determined. as an optimal formulation. Performing a hemolysis test and assessing the integrity of the erythrocyte membrane confirmed the biocompatibility of the prepared NPs. The higher rough surface of the NPs observed by atomic force microscopy (AFM) analysis suggested the possibility of vector conjugation.
Reference
Bhattacharya, S., Singh, D., Aich, J., Ajazuddin and Shete, M (2022). Development and characterization of hyaluronic acid surface scaffolds Polymer nanoparticles loaded with Encorafenib for colorectal cancer targeting. Materials Today Communications. https://www.sciencedirect.com/science/article/pii/S2352492822006171
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