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Oral delivery of paclitaxel by polymeric micelles: A comparison of different block length on uptake, permeability and oral bioavailability.

Abstract

Drug solubility and permeability are two major challenges affecting oral delivery, the most popular route of drug administration. Polymeric micelles is an emerging technology for overcoming the current oral drug delivery hurdles. Previous study primarily focused on developing new polymers or new micellar systems and a systematic investigation of the impact of the polymer block length on solubility and permeability enhancement; and their subsequent effect on oral bioavailability is lacking. Herein, by using paclitaxel, a poorly soluble P-glycoproteins (P-gp) substrate, as a model, we aim to assess and compare the drug-loaded micelles prepared with two different molecular weight of poly(ethylene glycol)-block-poly(ε-caprolactone) (PEG-b-PCL), with the ultimate goal of establishing a strong scientific rationale for proper design of formulations for oral drug delivery. PEG-b-PCL (750:570) (PEG17-b-PCL5) and PEG-b-PCL (5k:10k) (PEG114-b-PCL88) effectively enhanced the solubility of paclitaxel compared to the free drug. PEG-b-PCL (750:570) increased both P-gp and non P-gp substrate cellular uptake and increased the apparent permeability coefficient of a P-gp substrate. In vivo animal study showed that PEG-b-PCL micelles efficiently enhanced the oral bioavailability of paclitaxel. In addition to solubility enhancement, polymer choice also plays a pivotal role in determining the oral bioavailability improvement, probably via permeation enhancement. In conclusion, the knowledge gained in this study enables rational design of polymeric micelles to overcome the current challenges of oral drug delivery and it also provides a basis for future clinical translation of the technology.

Authors+Show Affiliations

School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong.School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong.School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong.Department of Pharmacology and Pharmacy, Faculty of Medicine, The University of Hong Kong, Hong Kong.Faculty of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, China.School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong.School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong.School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong. Electronic address: thomas.lee@aptorumgroup.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31627103

Citation

Sze, Lai Pan, et al. "Oral Delivery of Paclitaxel By Polymeric Micelles: a Comparison of Different Block Length On Uptake, Permeability and Oral Bioavailability." Colloids and Surfaces. B, Biointerfaces, vol. 184, 2019, p. 110554.
Sze LP, Li HY, Lai KLA, et al. Oral delivery of paclitaxel by polymeric micelles: A comparison of different block length on uptake, permeability and oral bioavailability. Colloids Surf B Biointerfaces. 2019;184:110554.
Sze, L. P., Li, H. Y., Lai, K. L. A., Chow, S. F., Li, Q., KennethTo, K. W., ... Lee, W. Y. T. (2019). Oral delivery of paclitaxel by polymeric micelles: A comparison of different block length on uptake, permeability and oral bioavailability. Colloids and Surfaces. B, Biointerfaces, 184, p. 110554. doi:10.1016/j.colsurfb.2019.110554.
Sze LP, et al. Oral Delivery of Paclitaxel By Polymeric Micelles: a Comparison of Different Block Length On Uptake, Permeability and Oral Bioavailability. Colloids Surf B Biointerfaces. 2019 Oct 6;184:110554. PubMed PMID: 31627103.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Oral delivery of paclitaxel by polymeric micelles: A comparison of different block length on uptake, permeability and oral bioavailability. AU - Sze,Lai Pan, AU - Li,Ho Yin, AU - Lai,Ka Lun Alan, AU - Chow,Shing Fung, AU - Li,Qingqing, AU - KennethTo,Kin Wah, AU - Lam,Tai Ning Teddy, AU - Lee,Wai Yip Thomas, Y1 - 2019/10/06/ PY - 2019/01/10/received PY - 2019/08/23/revised PY - 2019/10/02/accepted PY - 2019/10/19/pubmed PY - 2019/10/19/medline PY - 2019/10/19/entrez KW - Oral drug delivery KW - PEG-b-PCL KW - Paclitaxel KW - Permeability KW - Pharmacokinetics KW - Polymeric micelles SP - 110554 EP - 110554 JF - Colloids and surfaces. B, Biointerfaces JO - Colloids Surf B Biointerfaces VL - 184 N2 - Drug solubility and permeability are two major challenges affecting oral delivery, the most popular route of drug administration. Polymeric micelles is an emerging technology for overcoming the current oral drug delivery hurdles. Previous study primarily focused on developing new polymers or new micellar systems and a systematic investigation of the impact of the polymer block length on solubility and permeability enhancement; and their subsequent effect on oral bioavailability is lacking. Herein, by using paclitaxel, a poorly soluble P-glycoproteins (P-gp) substrate, as a model, we aim to assess and compare the drug-loaded micelles prepared with two different molecular weight of poly(ethylene glycol)-block-poly(ε-caprolactone) (PEG-b-PCL), with the ultimate goal of establishing a strong scientific rationale for proper design of formulations for oral drug delivery. PEG-b-PCL (750:570) (PEG17-b-PCL5) and PEG-b-PCL (5k:10k) (PEG114-b-PCL88) effectively enhanced the solubility of paclitaxel compared to the free drug. PEG-b-PCL (750:570) increased both P-gp and non P-gp substrate cellular uptake and increased the apparent permeability coefficient of a P-gp substrate. In vivo animal study showed that PEG-b-PCL micelles efficiently enhanced the oral bioavailability of paclitaxel. In addition to solubility enhancement, polymer choice also plays a pivotal role in determining the oral bioavailability improvement, probably via permeation enhancement. In conclusion, the knowledge gained in this study enables rational design of polymeric micelles to overcome the current challenges of oral drug delivery and it also provides a basis for future clinical translation of the technology. SN - 1873-4367 UR - https://www.unboundmedicine.com/medline/citation/31627103/Oral_delivery_of_paclitaxel_by_polymeric_micelles:_A_comparison_of_different_block_length_on_uptake,_permeability_and_oral_bioavailability L2 - https://linkinghub.elsevier.com/retrieve/pii/S0927-7765(19)30698-8 DB - PRIME DP - Unbound Medicine ER -