Lipoparticles for Synergistic Chemo-Photodynamic Therapy to Ovarian Carcinoma Cells: In vitro and in vivo Assessments

Abstract

Sajid Ali,1 Muhammad Umair Amin,1,2 Imran Tariq,1,3 Muhammad Farhan Sohail,4,5 Muhammad Yasir Ali,1,6 Eduard Preis,1 Ghazala Ambreen,1 Shashank Reddy Pinnapireddy,1 Jarmila Jedelská,1 Jens Schäfer,1 Udo Bakowsky1 1Department of Pharmaceutics and Biopharmaceutics, University of Marburg, Marburg, Germany; 2Faculty of Pharmacy, The University of Lahore, Lahore, Pakistan; 3Punjab University College of Pharmacy, University of the Punjab, Allama Iqbal Campus, Lahore, Pakistan; 4Riphah Institute of Pharmaceutical Sciences (RIPS), Riphah International University, Lahore, Pakistan; 5Department of Pharmacy, Faculty of Health and Medical Science, University of Copenhagen, Copenhagen, Denmark; 6Faculty of Pharmaceutical Sciences, GC University Faisalabad, Faisalabad, PakistanCorrespondence: Udo BakowskyDepartment of Pharmaceutics and Biopharmaceutics, University of Marburg, Robert Koch Str. 4, Marburg, 35037, GermanyTel + 49 6421 28 25884Fax + 49 6421 28 27016Email [email protected]: Lipoparticles are the core-shell type lipid-polymer hybrid systems comprising polymeric nanoparticle core enveloped by single or multiple pegylated lipid layers (shell), thereby melding the biomimetic properties of long-circulating vesicles as well as the mechanical advantages of the nanoparticles. The present study was aimed at the development of such an integrated system, combining the photodynamic and chemotherapeutic approaches for the treatment of multidrug-resistant cancers.Methods: For this rationale, two different sized Pirarubicin (THP) loaded poly lactic-co-glycolic acid (PLGA) nanoparticles were prepared by emulsion solvent evaporation technique, whereas liposomes containing Temoporfin (mTHPC) were prepared by lipid film hydration method. Physicochemical and morphological characterizations were done using dynamic light scattering, laser doppler anemometry, atomic force microscopy, and transmission electron microscopy. The quantitative assessment of cell damage was determined using MTT and reactive oxygen species (ROS) assay. The biocompatibility of the nanoformulations was evaluated with serum stability testing, haemocompatibility as well as acute in vivo toxicity using female albino (BALB/c) mice.Results and Conclusion: The mean hydrodynamic diameter of the formulations was found between 108.80 ± 2.10 to  405.70 ± 10.00 nm with the zeta (ζ) potential ranging from − 12.70 ± 1.20 to 5.90 ± 1.10 mV. Based on the physicochemical evaluations, the selected THP nanoparticles were coated with mTHPC liposomes to produce lipid-coated nanoparticles (LCNPs). A significant (p< 0.001) cytotoxicity synergism was evident in LCNPs when irradiated at 652 nm, using an LED device. No incidence of genotoxicity was observed as seen with the comet assay. The LCNPs decreased the generalized in vivo toxicity as compared to the free drugs and was evident from the serum biochemical profile, visceral body index, liver function tests as well as renal function tests. The histopathological examinations of the vital organs revealed no significant evidence of toxicity suggesting the safety and efficacy of our lipid-polymer hybrid system.Keywords: atomic force microscopy, FACS, in vivo, in vitro cytotoxicity, lipid-polymer hybrid nanoparticles, photodynamic therapy, PLGA nanoparticles, TEM

Keywords

• atomic force microscopy
• facs
• in vivo
• in vitro cytotoxicity
• lipid-polymer hybrid nanoparticles
• photodynamic therapy
• plga nanoparticles
• tem