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. 2010 Nov 30;401(1-2):79-86.
doi: 10.1016/j.ijpharm.2010.08.029. Epub 2010 Aug 27.

Novel pH-sensitive polyacetal-based block copolymers for controlled drug delivery

Jin-Ki Kim  1 , Vivek Kumar Garripelli, Ui-Hyeon Jeong, Jeong-Sook Park, Michael A Repka, Seongbong Jo
Affiliations

Novel pH-sensitive polyacetal-based block copolymers for controlled drug delivery

Jin-Ki Kim et al. Int J Pharm. .

Abstract

The principal aim of this study was to synthesize and characterize pH-sensitive biodegradable triblock copolymers containing a hydrophobic polyacetal segment for controlled drug delivery. Poly(ethylene glycol)-poly(ethyl glyoxylate)-poly(ethylene glycol) (PEG-PEtG-PEG) triblock copolymers with PEG molecular weights 500 (PEtG-PEG(500)) and 750 (PEtG-PEG(750)) were synthesized by PEtG end-capping with methoxy PEG via a carbamate linkage. Synthesized amphiphilic PEG-PEtG-PEG was characterized by (1)H NMR spectroscopy. Molecular weights of PEtG-PEG(500) and PEtG-PEG(750) were determined to be 2823 and 3387, respectively, by gel permeation chromatography. The polymers with a biodegradable polyacetal block underwent pH-dependent degradation via an acid-catalyzed hydrolysis. Paclitaxel (PTX)-loaded polymeric micelles were prepared by a dialysis method and the amount of PTX incorporated into the polymeric micelle formulations was 45,000 times greater than the water solubility of PTX at room temperature. The polymeric micelles prepared from the amphiphilic PEG-PEtG-PEG triblock copolymers have released the loaded PTX in a pH-dependent manner. The novel PEtG-based amphiphilic block copolymers can find applications for targeted and controlled drug delivery to the acidic environments found in tumors and intracellular compartments.

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Figures

Figure 1
Figure 1
Reaction scheme for the synthesis of PEG-PEtG-PEG block copolymers.
Figure 2
Figure 2
1H NMR spectrum of PEtG-PEG500 in CDCl3
Figure 3
Figure 3
pH-dependent degradation of PEtG-PEG750 determined by GPC measurements. Phosphate buffers of pHs 5.0, 6.5 and 7.4 were used for polymer degradation. The PEG-PEtG-PEG block copolymers released free mPEG upon polymer degradation.
Figure 4
Figure 4
TEM images of (a) PTX-free and (b) PTX-loaded polymeric micelles prepared from PEtG-PEG500
Figure 5
Figure 5
PTX release from (a) PEtG-PEG500 polymeric micelles and (b) PEtG-PEG750 polymeric micelles at pHs 5.0, 6.5 and 7.4. Phosphate buffer solutions containing 0.8 M sodium salicylate were used as release media. *Significant difference from the cumulative percent PTX release at pH 6.5 after 6 h drug release (p<0.05). **Significant difference from the cumulative percent PTX release at pH 7.4 after 6 h drug release (p<0.05). The results are expressed as the mean ± SD (n=3).
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