pH-Responsive Hybrid Nanoassemblies for Cancer Treatment: Formulation Development, Optimization, and In Vitro Therapeutic Performance

Abstract

Current needs for increased drug delivery carrier efficacy and specificity in cancer necessitate the adoption of intelligent materials that respond to environmental stimuli. Therefore, we developed and optimized pH-triggered drug delivery nanoassemblies that exhibit an increased release of doxorubicin (DOX) in acidic conditions typical of cancer tissues and endosomal vesicles (pH 5.5) while exhibiting significantly lower release under normal physiological conditions (pH 7.5), indicating the potential to reduce cytotoxicity in healthy cells. The hybrid (polymeric/lipid) composition of the lyotropic non-lamellar liquid crystalline (LNLCs) nanoassemblies demonstrated high encapsulation efficiency of the drug (>90%) and high drug loading content (>7%) with colloidal stability lasting at least 4 weeks. Confocal microscopy revealed cancer cellular uptake and DOX-loaded LNLCs accumulation near the nucleus of human hepatocellular carcinoma cells, with a large number of cells appearing to be in apoptosis. DOX-loaded LNLCs have also shown higher citotoxicity in cancer cell lines (MDA-MB 231 and HepG2 cell lines after 24 h and in NCI-H1299 cell line after 48 h) when compared to free drug. After 24 h, free DOX was found to have higher cytotoxicity than DOX-loaded LNLCs and empty LNLCs in the normal cell line. Overall, the results demonstrate that DOX-loaded LNLCs have the potential to be explored in cancer therapy.

Elastic Liposomes Containing Calcium/Magnesium Ferrite Nanoparticles Coupled with Gold Nanorods for Application in Photothermal Therapy

“…A stability study was performed to determine whether these magneto-plasmonic elastic liposomes satisfy the requirements for commercial and clinical outcome. For that purpose, mean size and PDI variations were monitored over a 20-day storage period at 4 °C ( Figure 8 ); considerable changes in these domains reveal signs of either aggregation or membrane rupture [ 62 ]. During this time, the MPELs size presented minimal shifts from the day 1 value (D 0 = 105.9 ± 4 nm; D 20 = 106.7 ± 3 nm), suggesting that these should remain stable in long-term storage.…”

Nanostructured Lipid Carriers Enriched Hydrogels for Skin Topical Administration of Quercetin and Omega-3 Fatty Acid

“…Regarding the zeta potential values, both NLCs are negatively charged. Even if NLC1 are composed of non-ionic surfactants, the presence of residual free fatty acids in soy lecithin (e.g., phosphatidic acid) [ 22 ] or poloxamer (e.g., resultant from polymer hydrolysis) confers a negative net charge to the formulations [ 51 ]. NLC2 composition includes an anionic surfactant, DOSS, which justifies the significantly lower (more negative) zeta potential values obtained for NLC2 than NLC1.…”

Click chemistry-based synthesis of new 1,2,3-triazolo-benzoquinoline-3-carbonitriles: anticancer screening and DFT studies

“…Existing antitumor chemotherapy still suffers from two major limitations. 3 The first is that conventional chemotherapeutic agents are not selective for cancer tissues, resulting in unwanted side effects. The second is that cancer cells have proved to be resistant to multiple drugs.…”