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AAPS PharmSciTech

, Volume 19, Issue 2, pp 693–699 | Cite as

Mixed Liposome Approach for Ratiometric and Sequential Delivery of Paclitaxel and Gemcitabine

  • Yuanfen Liu
  • Hassan Tamam
  • Yoon YeoEmail author
Research Article

Abstract

Paclitaxel (PTX) and gemcitabine (GEM) are often used in combination due to the synergistic anticancer effects. PTX and GEM combination showed a synergistic effect to SKOV-3 cells at a molar ratio of 1 to 1 and in PTX ➔ GEM sequence. Liposomes were explored as a carrier of PTX and GEM combination. We optimized the drug loading in liposomes varying the preparation method and co-encapsulated PTX and GEM in a single liposome preparation maintaining the maximum loading efficiency of each drug. However, drug release kinetics from the co-loaded liposomes (LpPG) was suboptimal because of the detrimental effect of PTX on GEM-release control. Instead, a mixture of LpP and LpG, which were separately optimized according to the desired release kinetics, achieved a greater cytotoxic effect than LpPG, due to the attenuation of GEM release relative to PTX. This study illustrates that co-encapsulation in a single carrier is not always desirable for the delivery of drug combinations, when the activity depends on the dosing sequence. These combinations may benefit from the mixed liposome approach, which offers greater flexibility in controlling the ratio and release kinetics of component drugs.

KEY WORDS

paclitaxel gemcitabine ratiometric combination delivery liposomes 

Notes

Acknowledgements

This work was supported by NIH R01 EB017791. We acknowledge the fellowship supports from the Jiangsu Overseas Research & Training Program for University Prominent Young Middle-aged Teachers for YL and the Egyptian Government Ministry of Higher Education Missions Sector for HT.

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Copyright information

© American Association of Pharmaceutical Scientists 2017

Authors and Affiliations

  1. 1.Jiangsu Jiankang Vocational CollegeNanjingChina
  2. 2.Department of Industrial and Physical PharmacyPurdue UniversityWest LafayetteUSA
  3. 3.Department of Industrial Pharmacy, Faculty of PharmacyAssiut UniversityAssiutEgypt
  4. 4.Weldon School of Biomedical EngineeringPurdue UniversityWest LafayetteUSA

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