Preparation of nanoparticles consisted of poly(l-lactide)–poly(ethylene glycol)–poly(l-lactide) and their evaluation in vitro
Introduction
Colloidal carriers are rapidly removed by the reticuloendothelial system (RES), because these particles are easily trapped by phagocytic cells. In recent years, various attempts have been made to change this (Illum and Davis, 1984, Senior et al., 1991, Müller et al., 1992, Stolnik et al., 1994).
Stolnik et al. (1994) showed that poly(lactide-co-glycolide) (PLGA) nanospheres coated biodegradable poly(l-lactide)–poly(ethylene glycol) copolymer (PLA–PEG) were less susceptible to hepatic uptake than naked PLGA nanospheres. PEG-PLGA nanospheres (Gref et al., 1994), methoxy PEG-PLA nanoparticles (Bazile et al., 1995), and PLA-PEG nanoparticles (Verrecchia et al., 1995) remained in the circulation a long time. These characteristics of diblock copolymer nanoparticles are due to the reduction of protein adsorption owing to the formation of a hydrophilic layer and a low surface charge originating in PEG (Stolnik et al., 1994). On the other hand, it was supposed to be difficult for triblock copolymer nanoparticles to evade the RES, because their hydrophilic PEG domains like those PLA–PEG–PLA do not move freely. But we have reported that nanoparticles using this PLA–PEG–PLA triblock copolymer evaded capture by the RES and remained a long time in the circulation (Nakada et al., 1997). The half-life after injection of 3H-progesterone loaded PLA–PEG–PLA nanoparticles was about twice that of 3H-progesterone-loaded PLA nanoparticles and the 3H-progesterone distribution to the liver and spleen after administration of 3H-progesterone PLA–PEG–PLA nanoparticles was about half that of 3H-progesterone PLA nanoparticles.
In this paper, we describe the characteristics of nanoparticles of this PLA–PEG–PLA triblock copolymer in vitro.
Section snippets
Materials
Progesterone, as a model hydrophobic compound with a very short half-life in blood, was purchased from Sigma (MO, USA). Polyoxyethylene (20) sorbitan monooleate (Polysorbate 80) and PEG (weight-average molecular weight (Mw); 6600 and 20 000, respectively) were of reagent grade from Wako Pure Chemical Industries (Osaka, Japan). Polyvinyl alcohol (PVA-203, Kuraray, Tokyo, Japan) was used as supplied. l-Lactide was purchased from Boehringer Ingelheim (Germany).
Polymerization
Bulk polymerization of l-lactide
Characterization of the nanoparticles
Progesterone nanoparticles were prepared by a solvent evaporation method. Values for the mean diameter of distribution and the drug trapping efficiency of each preparations are summarized in Table 3. A typical size distribution graph based on weight is presented in Fig. 1.
The nanoparticles had a mean diameter of 193–335 nm and trapping efficiencies of 65–74%. Both the mean diameter and the trapping efficiency were independent of the polymer composition in this study.
Effect of the release test conditions
The drug release behavior of
Conclusion
In conclusion, we studied progesterone-loaded PLA–PEG–PLA nanoparticles whose release appears to be controlled by the hydrophilic segments introduced into the hydrophobic parent PLA polymer. The amount of drug released was greater with the higher PEG content and Mw, and the lower total Mw of the polymers. Therefore, the drug release from nanoparticles was potentially controlled by PEG content, PEG Mw, and total Mw of the copolymer. Mw/Mn was also an important parameter in the control of drug
References (13)
- et al.
Stealth Me.PEG-PLA nanoparticles avoid uptake by the mononuclear phagocytes system
J. Pharm. Sci.
(1995) - et al.
In vitro characterization of poly(methyl-methacrylate) nanospheres and correlation to their in vivo fate
J. Control. Release
(1992) - et al.
Preparation of biodegradable nanospheres of water-soluble and insoluble drugs with d,l-lactide/glycolide copolymer by a novel spontaneous emulsification solvent diffusion method and the drug release behavior
J. Control. Release
(1993) - et al.
PEG coated nanospheres from amphiphilic diblock and multiblock copolymers: investigation of their drug encapsulationand release characteristics
J. Control. Release
(1997) - et al.
Influence of surface hydrophilicity of liposomes on their interaction with plasma protein and clearance from the circulation: studies with poly(ethylkene glycol)-coated vesicles
Biochim. Biophys. Acta
(1991) - et al.
Non-stealth (poly(lactic acid/albumin)) and stealth (poly(lactic acid-polyethylene glycol)) nanoparticles as injectable drug carriers
J. Control. Release
(1995)
Cited by (123)
Advance nanotherapeutic approach for systemic co-delivery of mitoxantrone loaded chitosan coated PLGA nanoparticles to improve the chemotherapy against human non-small cell lung cancer
2023, Journal of Drug Delivery Science and TechnologyElectrospun biopolymer-based hybrid composites
2021, Hybrid Natural Fiber Composites: Material Formulations, Processing, Characterization, Properties, and Engineering ApplicationsComposites based on bioderived polymers: Potential role in tissue engineering: Vol VI: Resorbable polymer fibers
2019, Materials for Biomedical Engineering: Hydrogels and Polymer-based ScaffoldsModeling of the burst release from PLGA micro- and nanoparticles as function of physicochemical parameters and formulation characteristics
2017, International Journal of PharmaceuticsCitation Excerpt :Likewise, PLS analysis suggests that lower PLGA/PEG ratios lead to a faster burst. These results are in agreement with (Avgoustakis et al., 2002; Vega et al., 2012; Kang, 2001; Morita et al., 2000; Matsumoto et al., 1999). Avgoustakis et al. (Avgoustakis et al., 2002) observed a correlation between the increase in the proportion of PEG in the copolymer chains and the amount of degradation of the PLGA-PEG particles.
Localised delivery of doxorubicin to prostate cancer cells through a PSMA-targeted hyperbranched polymer theranostic
2017, BiomaterialsCitation Excerpt :There exist many examples in the literature in which nanoparticles have demonstrated their versatility through functionalisation with various components for imaging, targeting and drug delivery, such as nanoparticles featuring active targeting ligands and encapsulating therapeutic drugs [25,26]. A further advantage of utilising a polymer based system is that the circulation times and clearance mechanisms of the nanoparticles are able to be tuned through manipulation of the properties of the carrier material, for example to allow long-term sustained released through controlled erosion, or capsule degradation at the active site through the use of biodegradable monomers [27–30]. The other important aspect that must be considered is how the drug will be incorporated into the nanoparticle.