Co-delivery of cisplatin and paclitaxel by folic acid conjugated amphiphilic PEG-PLGA copolymer nanoparticles for the treatment of non-small lung cancer

Abstract

An amphiphilic copolymer, folic acid (FA) modified poly(ethylene glycol)-poly(lactic-co-glycolic acid) (FA-PEG-PLGA) was prepared and explored as a nanometer carrier for the co-delivery of cisplatin (cis-diaminodichloroplatinum, CDDP) and paclitaxel (PTX). CDDP and PTX were encapsulated inside the hydrophobic inner core and chelated to the middle shell, respectively. PEG provided the outer corona for prolonged circulation. An in vitro release profile of the CDDP + PTX-encapsulated nanoparticles revealed that the PTX chelation cross-link prevented an initial burst release of CDDP. After an incubation period of 24 hours, the CDDP+PTX-encapsulated nanoparticles exhibited a highly synergistic effect for the inhibition of A549 (FA receptor negative) and M109 (FA receptor positive) lung cancer cell line proliferation. Pharmacokinetic experiment and distribution research shows that nanoparticles have longer circulation time in the blood and can prolong the treatment times of chemotherapeutic drugs. For the in vivo treatment of A549 cells xeno-graft lung tumor, the CDDP+PTX-encapsulated nanoparticles displayed an obvious tumor inhibiting effect with an 89.96% tumor suppression rate (TSR). This TSR was significantly higher than that of free chemotherapy drug combination or nanoparticles with a single drug. For M109 cells xeno-graft tumor, the TSR was 95.03%. In vitro and in vivo experiments have all shown that the CDDP+PTX-encapsulated nanoparticles have better targeting and antitumor effects in M109 cells than CDDP+PTX-loaded PEG-PLGA nanoparticles (p < 0.05). In addition, more importantly, the enhanced anti-tumor efficacy of the CDDP+PTX-encapsulated nanoparticles came with reduced side-effects. No obvious body weight loss or functional changes occurred within blood components, liver, or kidneys during the treatment of A549 and M109 tumor-bearing mice with the CDDP+PTX-encapsulated nanoparticles. Thus, the FA modified amphiphilic copolymer-based combination of CDDP and PTX may provide useful guidance for effective and safe cancer chemotherapy, especially in tumors with high FA receptor expression.

Dendrimer antibody conjugate to target and image HER-2 overexpressing cancer cells

“…Additionally, the sizes and polydispersity indexes (PDI) of the dendrimers can easily be controlled [2, 3] and they are biocompatible [4]. Therefore, dendrimers are attractive macromolecules for drug delivery and molecular imaging [5, 6]. In particular, polyamidoamine (PAMAM) dendrimers have a narrow polydispersity and contain terminal amines that can be conjugated with targeting agents, therapeutics, and imaging agents for drug delivery and in vitro imaging [7–9].…”

Co-delivery of etoposide and curcumin by lipid nanoparticulate drug delivery system for the treatment of gastric tumors

“…Also, with the obvious reduced dosage of ETP and CUR used for the drug-loaded NLCs, ETP-CUR-NLCs showed significantly higher in vivo tumor inhibition effect than the ETP-NLCs and CUR-NLCs. This could prove that the ETP and CUR-loaded in the NLCs have a synergistic effect: the dosage of both drugs could be reduced to a large content (He et al, 2015). This could help with the reduction of the unexpected side effect during the cancer therapy procedure, and could also bring about excellent anti-tumor efficiency.…”

Immune activity and biodistribution of polypeptide K237 and folic acid conjugated amphiphilic PEG-PLGA copolymer nanoparticles radiolabeled with 99mTc

“…Previous studies have revealed that K237/FA-PEG-PLGA (LA/GA = 80/20) has better physicochemical properties and biocompatibility [27–30, 47–49]. Accordingly, the tumor-targeting properties of the preparations with the most favorable biodistribution, K237/FA-PEG-PLGA (LA/GA = 80/20) NPs was studied in mice xenografted with SKOV-3 cells.…”