Doxorubicin and β-Lapachone Release and Interaction with Micellar Core Materials: Experiment and Modeling

Abstract

Polymer micelles with two different core-forming blocks, poly(d,l -lactide) (PLA) and poly(epsilon-caprolactone) (PCL), but the same coronal material, poly(ethylene glycol) (PEG), were investigated in this study as nanoscopic drug carriers. The release of two different drugs, doxorubicin (DOX) and beta-lapachone (beta-lap), from PEG(5k)-b-PCL(5k) and PEG(5k)-b-PLA(5k) micelles was studied at pH 5.0 and 7.4. Mathematical solutions of both Higuchi's model and Fickian diffusion equations were utilized to elucidate the differences between the micelle core materials for the two drugs. The neutral and smaller of the two drugs tested, beta-lap, demonstrated faster, pH-independent release, suggesting that no substantial changes occurred in either micelle core at lower pH. In contrast, the release rate of DOX was found to noticeably increase at lower pH with a larger cumulative amount of drug released. Different core materials were shown to have considerable influence on the release kinetics of both drugs: in both cases, the more hydrophobic PCL core showed slower drug release rates compared with the less hydrophobic PLA core.

Investigation on design of stable etoposide-loaded PEG-PCL micelles: effect of molecular weight of PEG-PCL diblock copolymer on thein vitroandin vivoperformance of micelles

“…Recently, polymeric micelles have been emerged as a novel nanomedicine platform for drug delivery, due to their smaller size, stability, versatility, and biocompatibility (Shen et al, 2007;Sutton et al, 2007). These micelles have demonstrated their ability to efficiently solubilize lipophilic agents with altered drug pharmacokinetics and in several cases have been reached to clinical trials (Allen et al, 2000;Matsumura et al, 2004;Zhang et al, 2004;Forrest et al, 2008;Lee et al, 2008;Xiong et al, 2008) Micelles made up of core-shell structure are normally fabricated by a self-assembly approach using amphiphilic block copolymers in a selective solvent in which the hydrophobic core part provides a cargo space for solubilization of various lipophilic drugs (Aliabadi et al, 2007;Molavi et al, 2008).…”

Preparation and Characterizations of RSPP050-Loaded Polymeric Micelles Using Poly(ethylene glycol)-<i>b</i>-Poly(ε-caprolactone) and Poly(ethylene glycol)-<i>b</i>-Poly(D,L-lactide)

“…The type of polymers used produced noticeable effect on the size of micelles where the size of PEG-b-PCL micelles was smaller than that of PEG-b-PLA; this was due to the more hydrophobic property of PEG-b-PCL that lead to less swollen structure and more compact micelle core. 14) Micelle size, drug loading contents (% DLC), encapsulation efficiency (% EE) and yields (% yields) of AG50-loaded PEG-b-PCL and PEG-b-PLA micelles were shown in Table 1.…”

“…The molecular weight of these copolymers can be varied which in turn controls the particle size, drug encapsulation, and drug release of the polymeric micelles. 13,14) Several methods for micelle preparations have been examined to encapsulate hydrophobic drug in polymeric micelles. Solvent evaporation method, film sonication, and dialysis method are widely used for micelle preparation.…”

“…Film sonication method was employed for micelles preparation because this method provided high drug loading content as a result of short preparation time. 14,15) Block copolymers with amphiphilic property were used to prepare micelles. These polymers composed of two different segments 16) including the outer shell segment and inner core segment.…”

MgH2/PEG initiating system for ring opening polymerization of lactone and lactide

“…Thus the above copolymerization can be depicted as in Scheme 1(with LA instead of CL). 13 C NMR spectrum of PLA-b-PEG-b-PLA ( Figure 5) showed peaks at 169.3 and 174.30 ppm attributed to the carbonyl group of the polyester blocks and peaks at 17.3 and 69.5 ppm attributed respectively to methyl and methine carbon atoms. First investigations based on 13 C NMR analysis also indicated that the stereochemistry of the chiral carbon atom of the L-lactide monomer CO-CH(CH 3 )-O was unchanged during the polymerization leading to the formation of stereoregular sequence as P(L-LA).…”