Synthesis, characterization, and evaluation of paclitaxel loaded in six-arm star-shaped poly(lactic-co-glycolic acid)

Abstract

Background Star-shaped polymers provide more terminal groups, and are promising for application in drug-delivery systems. Methods A new series of six-arm star-shaped poly(lactic-co-glycolic acid) (6-s-PLGA) was synthesized by ring-opening polymerization. The structure and properties of the 6-s-PLGA were characterized by carbon-13 nuclear magnetic resonance spectroscopy, infrared spectroscopy, gel permeation chromatography, and differential scanning calorimetry. Then, paclitaxel-loaded six-arm star-shaped poly(lactic-co-glycolic acid) nanoparticles (6-s-PLGA-PTX-NPs) were prepared under the conditions optimized by the orthogonal testing. High-performance liquid chromatography was used to analyze the nanoparticles’ encapsulation efficiency and drug-loading capacity, dynamic light scattering was used to determine their size and size distribution, and transmission electron microscopy was used to evaluate their morphology. The release performance of the 6-s-PLGA-PTX-NPs in vitro and the cytostatic effect of 6-s-PLGA-PTX-NPs were investigated in comparison with paclitaxel-loaded linear poly(lactic-co-glycolic acid) nanoparticles (L-PLGA-PTX-NPs). Results The results of carbon-13 nuclear magnetic resonance spectroscopy and infrared spectroscopy suggest that the polymerization was successfully initiated by inositol and confirm the structure of 6-s-PLGA. The molecular weights of a series of 6-s-PLGAs had a ratio corresponding to the molar ratio of raw materials to initiator. Differential scanning calorimetry revealed that the 6-s-PLGA had a low glass transition temperature of 40°C–50°C. The 6-s-PLGA-PTX-NPs were monodispersed with an average diameter of 240.4±6.9 nm in water, which was further confirmed by transmission electron microscopy. The encapsulation efficiency of the 6-s-PLGA-PTX-NPs was higher than that of the L-PLGA-PTX-NPs. In terms of the in vitro release of nanoparticles, paclitaxel (PTX) was released more slowly and more steadily from 6-s-PLGA than from linear poly(lactic-co-glycolic acid). In the cytostatic study, the 6-s-PLGA-PTX-NPs and L-PLGA-PTX-NPs were found to have a similar antiproliferative effect, which indicates durable efficacy due to the slower release of the PTX when loaded in 6-s-PLGA. Conclusion The results suggest that 6-s-PLGA may be promising for application in PTX delivery to enhance sustained antiproliferative therapy.

In vitro anticancer activity of folate-modified docetaxel-loaded PLGA nanoparticles against drug-sensitive and multidrug-resistant cancer cells

“…In general, this causes a delay in the induction of cell death by docetaxel-and paclitaxel-loaded nanoparticles compared to free drug (Danhier et al 2009). This might be the reason why authors sometimes do not provide comparative data on cytotoxicity of free drug and drug-loaded polymeric nanoparticles, since the obtained results are obviously not in favor of the latter (Chen et al 2013;Ma et al 2010). However, it should be kept in mind that docetaxel does not cause immediate cell death as this drug induces cytotoxicity by altering the rate and degree of microtubule polymerization and suppressing microtubule dynamics, which leads to inhibition of centrosome duplication in the S-phase (Paoletti et al 1997), disruption of the mitotic spindle formation and Table 3 The cytostatic activity of F-NP-Doc versus free docetaxel expressed as IC50 value HeLa cells were incubated with F-NP-Doc and docetaxel for 24, 48 and 72 h. Cell survival was assessed using the SRB assay (Hernandez-Vargas et al 2007).…”

The Design of Poly(lactide-co-glycolide) Nanocarriers for Medical Applications

“…Polymer-based nanoparticles act as drug delivery vehicles by encapsulating the active agent inside its polymeric matrix, by conjugating to the agent or by adsorbing it onto the surface of the polymer (Mahapatro and Singh, 2011;Ansary et al, 2014). Polymers can be constructed to be linear, branched or globular and their size and their properties can be modulated by the choice of synthetic process (Panyam and Labhasetwar, 2012;Chen et al, 2013). Biodegradable polymers are suitable as nanocarriers as they often self-assemble and are easily sourced.…”

Polydopamine-tailored paclitaxel-loaded polymeric microspheres with adhered NIR-controllable gold nanoparticles for chemo-phototherapy of pancreatic cancer

“…In particular, the therapeutic efficacy of chemotherapeutic drugs is known to be improved when photothermal therapy (PTT) is used in combination with a strong near-infrared red (NIR) light for conversion of light into heat (Chen et al., 2017). Among several plasmonic photothermal agents, gold nanoparticles (GNPs) have gained popularity for PTT, since they are capable of scattering and absorbing light in the NIR region, and can convert the incident photons into high photothermal energy to induce cell death (Chen et al., 2013; Tran et al., 2016). Compared to the traditional organic dyes, such as rhodamine 6G (Wang et al., 2014) and indocyanine green (Zheng et al., 2011), GNPs offer several-fold higher photo stability (Banstola et al., 2018), and possess high photothermal conversion efficiency (Huang et al., 2008; Emami et al., 2019; Poudel et al., 2019).…”