Abstract Title:

In vitro and in vivo evaluation ofΔ⁹-tetrahidrocannabinol/PLGA nanoparticles for cancer chemotherapy.

Abstract Source:

Int J Pharm. 2015 Jun 20 ;487(1-2):205-12. Epub 2015 Apr 18. PMID: 25899283

Abstract Author(s):

L Martín-Banderas, I Muñoz-Rubio, J Prados, J Álvarez-Fuentes, J M Calderón-Montaño, M López-Lázaro, J L Arias, M C Leiva, M A Holgado, M Fernández-Arévalo

Article Affiliation:

L Martín-Banderas


Nanoplatforms can optimize the efficacy and safety of chemotherapy, and thus cancer therapy. However, new approaches are encouraged in developing new nanomedicines against malignant cells. In this work, a reproducible methodology is described to prepareΔ(9)-tetrahidrocannabinol (Δ(9)-THC)-loaded poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles against lung cancer. The nanoformulation is further improved by surface functionalization with the biodegradable polymers chitosan and poly(ethylene glycol) (PEG) in order to optimize the biological fate and antitumor effect. Mean nanoparticle size (≈ 290 nm) increased upon coating with PEG, CS, and PEG-CS up to ≈ 590 nm, ≈ 745 nm, and ≈ 790 nm, respectively. Surface electrical charge was controlled by the type of polymeric coating onto the PLGA particles. Drug entrapment efficiencies (≈95%) were not affected by any of the polymeric coatings. On the opposite, the characteristic sustained (biphasic) Δ(9)-THC release from the particles can be accelerated or slowed down when using PEG or chitosan, respectively. Blood compatibility studies demonstrated the adequate in vivo safety margin of all of the PLGA-based nanoformulations, while protein adsorption investigations postulated the protective role of PEGylation against opsonization and plasma clearance. Cell viability studies comparing the activity of the nanoformulations against human A-549 and murine LL2 lung adenocarcinomacells, and human embryo lung fibroblastic MRC-5 cells revealed a statistically significant selective cytotoxic effect toward the lung cancer cell lines. In addition, cytotoxicity assays in A-549 cells demonstrated the more intense anticancer activity of Δ(9)-THC-loaded PEGylated PLGA nanoparticles.These promising results were confirmed by in vivo studies in LL2 lung tumor-bearing immunocompetent C57BL/6 mice.

Study Type : Animal Study, In Vitro Study

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