The in vitro and in vivo anti-tumor effects of MTX-Fe3O4-PLLA-PEG-PLLA microspheres prepared by suspension-enhanced dispersion by supercritical CO2

Abstract

The in vitro and in vivo anti-tumor efficacy of methotrexate-loaded Fe 3 O 4 -poly-L-lactide-poly(ethylene glycol)-poly-L-lactide magnetic composite microspheres (MTX-Fe 3 O 4 -PLLA-PEG-PLLA MCMs, MMCMs), which were produced by co-precipitation (C) and microencapsulation (M) in a supercritical process, was evaluated at various levels: cellular, molecular, and integrated. The results at the cellular level indicate that MMCMs (M) show a better anti-proliferation activity than raw MTX and could induce morphological changes of cells undergoing apoptosis. At the molecular level, MMCMs (M) lead to a significantly higher relative mRNA expression of bax/bcl-2 and caspase-3 than MMCMs (C) at 10 µg mL 1 (P<0.01); and the pro-caspase-3 protein expression measured by Western blot analysis also demonstrates that MMCMs (M) can effectively activate pro-caspase-3. At the integrated level, mice bearing a sarcoma-180 tumor are used; in vivo anti-tumor activity tests reveal that MMCMs (M) with magnetic induction display a much higher tumor suppression rate and lower toxicity than raw MTX. Pharmacokinetic studies show that MMCMs (M) with magnetic induction significantly increase the accumulation of MTX in the tumor tissue compared with the other treatments. These results suggest that the MMCMs (M) prepared by the SpEDS process have great potential to play a positive role in the magnetic targeted therapy field.

Preparation and antitumor effect evaluation of composite microparticles co-loaded with siRNA and paclitaxel by a supercritical process

“…12, it can be observed that many dead cells existed in the group of siRNA-PTX-CMPs within 48 hours, demonstrating 85 that the CMPs based on PLLA-PEG-PLLA had entered the cells and achieved a good antitumor effect. Chen et al 47 used methotrexate-loaded PLLA-PEG-PLLA microparticles in the treatment of MG-63 cells and concluded that the drug-loaded microparticles could induce the apoptosis and death of cells, and 90 this supports the above findings. As shown in Fig.…”

The In Vivo Pharmacokinetics of Block Copolymers Containing Polyethylene Glycol Used in Nanocarrier Drug Delivery Systems

“…block copolymers such as diblock polymers(PEG-PLA) and tri-block polymers(PLA-PEG-PLA) have a wide range of effects, which can be used to increase the drug load of hydrophobic drugs, prolong blood circulation time, improve drug bioavailability and efficacy (Xiao et al, 2010;Chen et al, 2014;Ghasemi et al, 2018;Goudarzi et al, 2018;Amani et al, 2019;Girard et al, 2021;Massadeh et al, 2021). Although in vivo fate studies of triblock PLA-PEG-PLA polymers have not been reported, pharmacokinetic studies of diblock PEG-PLA polymers in rats after i.v.…”

Supercritical Fluid Technology: An Emphasis on Drug Delivery and Related Biomedical Applications

“…[ 4a ] Moreover, traditional methods undergo a multi-step process to manufacture dosage forms. Increased demand of pharmaceutical industries in developing new approaches for drug delivery, has evidenced the SCF technology as an alternative [ 55 ] for the syntheses of micro- [ 35 , 56 ] as well as nano-size particles [ 20d,e , 57 ] with homogenous size distribution and high-performance. [ 21a ] Indeed, this technology has been used to manufacture various formulations of different drug categories such as those treating anesthesia, [ 58 ] antibiotics, [ 53 , 59 ] asthma, [ 60 ] cancer, [ 61 ] central nervous system, [ 62 ] cardiovascular system, [ 31a ] diabetes, [ 28 ] diuretics, [ 63 ] inflammation (steroidal [ 64 ] and non-steroidal anti-inflammatory agents [ 65 ] ), lipid-lowering, [ 66 ] among others, administered through oral, [ 67 ] intravenous, [ 41 ] ophthalmic, [ 68 ] pulmonary, [ 47 ] transdermal, [ 61c ] and polymeric implants for sustained delivery.…”