Alpha-Mangostin-Loaded Transferrin-Conjugated Lipid-Polymer Hybrid Nanoparticles: Development and Characterization for Tumor-Targeted Delivery

Abstract

Alpha-mangostin, a natural xanthone mainly extracted from the pericarp of Garcinia mangostana, has been shown to have promising anticancer properties in many types of cancer. However, the therapeutic potential of α-mangostin has been limited so far due to its poor aqueous solubility and low oral bioavailability, which limited its biopharmaceutical applications. Furthermore, α-mangostin failed to specifically reach tumors at a therapeutic concentration due and rapid elimination in vivo. We hypothesized that this drawback could be overcome by loading the drug within a delivery system conjugated to transferrin (Tf), whose receptors are overexpressed on many cancer cells and would enhance the specific delivery of α-mangostin to cancer cells, thereby enhancing its therapeutic efficacy. The objectives of this study were therefore to prepare and characterize transferrin-conjugated lipid-polymer hybrid nanoparticles (LPHN) entrapping α-mangostin, as well as to evaluate their therapeutic efficacy in vitro. We successfully prepared α-mangostin loaded LPHN using a one-step nanoprecipitation method with high drug entrapment efficiency. The conjugation of Tf to the LPHN was achieved by using the thiol–maleimide “click” reaction, leading to an increase in the particle hydrodynamic size of Tf-LPHN compared to that of unconjugated (control) LPHN (Ctrl-LPHN). Both Tf-LPHN and Ctrl-LPHN were bearing negative surface charges. Tf-LPHN and Ctrl-LPHN exhibited a sustained release of α-mangostin at pH 7.4, following an initial burst release, unlike rapid release of drug solution. The entrapment of α-mangostin in the LPHN led to an increase in α-mangostin uptake by cancer cells, and thus improved its antiproliferative activity compared to that observed with the drug solution. In conclusion, α-mangostin entrapped in the Tf-LPHN is therefore a highly promising therapeutic system that should be further optimized as therapeutic tools for cancer treatment.

Preparation and evaluation of a niosomal delivery system containing G. mangostana extract and study of its anti-Acanthamoeba activity

“… 28 Sakpakdeejaroen and colleagues reported enhanced cellular accumulation when α-mangostin was entrapped in transferrin-conjugated lipid polymer hybrid nanoparticles and found to be effective in antiproliferative activity of various cancer cell lines. 29 Therefore, transferrin-conjugated lipid polymer hybrid nanoparticle is a highly promising therapeutic system that should be further optimized as therapeutic tools for cancer treatment. 29 …”

“… 29 Therefore, transferrin-conjugated lipid polymer hybrid nanoparticle is a highly promising therapeutic system that should be further optimized as therapeutic tools for cancer treatment. 29 …”

“…28 Sakpakdeejaroen and colleagues reported enhanced cellular accumulation when a-mangostin was entrapped in transferrin-conjugated lipid polymer hybrid nanoparticles and found to be effective in antiproliferative activity of various cancer cell lines. 29 Therefore, transferrin-conjugated lipid polymer hybrid nanoparticle is a highly promising therapeutic system that should be further optimized as therapeutic tools for cancer treatment. 29 This study we selected a 1 : 1 ratio of span 60 and cholesterol for niosome preparation which it is oen based on a combination of factors related to the stability, structural properties, and performance of niosomes.…”

Surface Functionalised Parenteral Nanoemulsions for Active and Homotypic Targeting to Melanoma

“…Alternatively, homotypic targeting is based upon the interaction among those adhesion proteins, which are present on the surface of cancer cells, and that can be used to coat the surface of nanoemulsion droplets [ 15 ]. Transferrin (TRF) has been frequently employed as the ligand for active targeting [ 16 , 17 , 18 ], since it shows a relatively high interspecies equivalence with respect to receptor binding [ 19 ] and its receptor is over-expressed in melanoma [ 16 ]. Literature evidence shows that nanoemulsions can be successfully conjugated to proteins by using maleimide-based linkers [ 20 ].…”

Cytotoxicity Enhancement of α-Mangostin with Folate-Conjugated Chitosan Nanoparticles in MCF-7 Breast Cancer Cells

“…Nanomicelle formation and polymeric nanoparticle encapsulation have been proven to enhance the solubility of AM and facilitate its targeted delivery to specific organs [18]. Various studies, conducted both in vitro and in vivo, have demonstrated the enhanced cytotoxicity, antiproliferative activity, and induction of apoptosis when AM is delivered through these nanoparticle systems, such as transferrin-conjugated lipid-polymer hybrid NPs [19], AM-encapsulated poly(lactic-co-glycolic) acid (PLGA) NPs [20], AM-CS/sodium alginate NPs [21], AM-CS/carrageenan NPs [22] and hyaluronic acid-coated CS-NPs [23]. Additionally, NPs constructed with crosslinked CS and glyoxal have demonstrated controlled-release properties, making them a promising drug-delivery system for hydrophobic compounds such as AM [24].…”