Poly(l-lactide- co-caprolactone- co-glycolide)-Based Nanoparticles as Delivery Platform: Effect of the Surfactants on Characteristics and Delivery Efficiency

Abstract

Polymeric nanoparticles made of the copolymer Poly(L-lactide-co-caprolactone-co-glycolide) were prepared using the solvent evaporation method. Two different surfactants, polyvinyl alcohol and dextran, and a mixture of the two were employed. The three types of nanoparticles were used as hosting carriers of two chemotherapeutic drugs, the hydrophilic doxorubicin and the hydrophobic SN-38. The morphostructural characterization showed similar features for the three types of nanoparticles, while the drug encapsulation efficiency indicated that the dextran-based systems are the most effective with both drugs. Cellular studies with breast cancer cells were performed to compare the delivery capability and the cytotoxicity profile of the three nanosystems. The results show that the unloaded nanoparticles are highly biocompatible at the administered concentrations and confirmed that dextran-coated nanoparticles are the most efficient vectors to release the two drugs, exerting cytotoxic activity. PVA, on the other hand, shows limited drug release in vitro, probably due to strong interactions with both drugs. Data also show the release is more efficient for doxorubicin than for SN-38; indeed, the doxorubicin IC₅₀ value for the dextran-coated nanoparticles was about 35% lower than the free drug. This indicates that these nanocarriers are suitable candidates to deliver hydrophilic drugs while needing further modification to host hydrophobic molecules.

Keywords: SN-38; doxorubicin; polymeric nanoparticle; surfactant-drug interaction.

Scheme 1

Illustration of the polymeric components of the NPs (the light yellow, light blue and orange curved lines correspond to PLCG, PVA and DEX, respectively), of the drugs (the red and green triangles correspond to DOXO and SN-38, respectively) encapsulated within them and of the main steps of the work.

Figure 1

FTIR spectra of (a) free PLGC polymer and surfactants; (b) NPs prepared with the different surfactants. *: peak shifted towards higher frequencies; **: ratios between this peak and that at 1759 cm⁻¹ decreases.

Figure 2

(a) TGA curves and corresponding (b) first derivatives of the PLCG NPs prepared with the different surfactants; (c) TGA curves and corresponding (d) first derivatives of free PLGC polymer and surfactants.

Scheme 2

Structure of the two drugs loaded into the nanoparticles, (a) DOXO and (b) SN-38.

Figure 3

Average dimensions of the NPs over time (up to 21 days). In the graph, the hollow symbols correspond to the empty NPs while the full ones to the NPs loaded with (a) DOXO and (b) SN-38. ■: PVA; ▼: DEX; ●: PVA/DEX.

Figure 4

TEM micrographs of the different NPs: (a) PVA, (b) PVA with DOXO, (c) PVA with SN-38, (d) DEX, (e) DEX with DOXO, (f) DEX with SN-38, (g) PVA/DEX, (h) PVA/DEX with DOXO, (i) PVA/DEX with SN-38.

Figure 5

DCF assay (reported as the fluorescence intensity/protein content, normalized to the control sample) performed with MCF-7 cells incubated with the NPs coated with the three types of surfactants and loaded with either (a) DOXO (for 72 h) or (b) SN-38 (for 120 h). The cells were administered with a drug concentration equal to 1 µM and 100 nM in the case of DOXO and SN-38, respectively. H₂O₂ treatment (1 mM) for 1 h was used as a positive control. (*) and (**) indicate statistical significance with p < 0.05 and 0.01, respectively.

Figure 6

Representative images of DCF staining in MCF-7 cells incubated with either the free drugs or with the PVA/DEX NPs, both empty and loaded. Panels (a,b) correspond to the fluorescence channel and to the bright field, respectively. The scale bar corresponds to 100 µm.

Figure 7

Release of the drugs from the NPs prepared with the different surfactants as a function of time. (a) DOXO at pH = 4.5; (b) DOXO at pH = 7; (c) SN-38 at pH = 4.5; (d) SN-38 at pH = 7.