Fabrication of psoralen-loaded lipid-polymer hybrid nanoparticles and their reversal effect on drug resistance of cancer cells

Abstract

In the present study, a lipid-polymer hybrid drug carrier system was developed to encapsulate psoralen (PSO), a multidrug resistance reversal agent and traditional Chinese medicine. Emphasis was focused the parameters that influence physicochemical characteristics, and then the drug release profile, stability, cytotoxicity and drug resistance reversal effect of the lipid-polymer hybrid nanoparticles (LPNs) were investigated. It was found that various formulation parameters affected NP size, drug loading (DL) and release characteristics. Hydrophilic 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-carboxy(polyethylene glycol)2000 increased the ζ potential and thus the stability of the NPs, but also enlarged their diameter. The amount of PSO influenced their DL and encapsulation efficiency, but did not show any effect on drug release kinetics. Next, the stability of the LPNs in different media and their storage characteristics were assessed. Finally, the cytotoxicity and multidrug resistance reversal effect was studied in the K562 and HepG2 cell lines. The analysis of half maximal inhibitory concentration values demonstrated that combination therapy with doxorubicin (DOX) and PSO-loaded LPNs (P-LPNs) was 14- and 23-fold more effective than a single-dose DOX treatment in resistant K562 and HepG2 cells, respectively, and 2.2- and 2.1-fold more effective than a single-dose combination regimen of DOX and PSO in solution, respectively. These data indicate that the LPNs have superior properties compared with a combination therapy in solution.

Nano-traditional Chinese medicine: a promising strategy and its recent advances

“…The size and polydispersity of these hybrid nanoparticles incubated in either PBS or RPMI-1640 medium did not change significantly over 120 h, indicating an appreciable stability. 150…”

“…The size and polydispersity of these hybrid nanoparticles incubated in either PBS or RPMI-1640 medium did not change significantly over 120 h, indicating an appreciable stability. 150 In general, well-designed hybrid nanoparticles can combine the advantages while avoiding the disadvantages, and thus could be considered as ideal drug delivery systems.…”

The state of the art in core-shell type lipid polymer hybrid nanocarriers and beyond

“…We begin this section by noting that this technique, shown in Figure 4, has prevailed over the evaporation of emulsifiers. In this modified technique, which combines the nanoprecipitation technique with the concept of self-assembly, the main aspect is that the active molecules and the polymers are dissolved in a water-miscible solvent such as acetone [42,43], ethanol [44], or acetonitrile [45]. Then, this solution is added to the aqueous solutions of lipids (e.g., PEG -conjugated or -unconjugated phospholipids) with continuous stirring, whereupon the lipid molecules and polymer particles spontaneously self-assemble in the solution (the lipid concentration in the solution should be high enough to surround the polymer core) [46].…”

Boosting the Skin Delivery of Curcumin Through Stearic Acid-Ethyl Cellulose Blend Hybrid Nanocarriers-Based Approach for Mitigating Psoriasis

“…During optimization, it was found that ethylcellulose concentration lower than 20 mg rendered the structure of nanoparticles and also chances for low drug entrapment, whereas greater than 20 mg or excess amounts of polymer concentration produced larger size of nanoparticles, mainly due to formation of aggregation, which is further decrease the drug release and biostability of formulations [50]. Further, stearic acid concentration lower than 5 mg leading to sediment at the bottom of the container due to precipitation and coalescence of the polymeric core resulting from incomplete lipid layer coverage, whereas greater than 5 mg or excess amounts of lipid concentration resulting in the formation of thick lipid layers, which is further increasing the particle size as well as causing some challenges during drug release [51]. Hence, for the preparation of stable nanoformulations, the amount of ethylcellulose and stearic acid was fixed at 20 mg and 5 mg, respectively, as optimal and chosen for subsequent experiments with the addition of varying amounts of the drug.…”