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Muhammad Muzamil Khan,1 Asadullah Madni,1 Nayab Tahir,2 Farzana Parveen,1 Safiullah Khan,1 Nasrullah Jan,1 Ahsan Ali,1 Muhammad Abdurrahim,1 Umar Farooq,3 Muhammad Imran Khan4 1Department of Pharmacy, The Islamia University of Bahawalpur, Bahawalpur, Pakistan; 2College of Pharmacy, University of Sargodha, Sargodha, Pakistan; 3Department of Pharmacy, Government College University Faisalabad, Faisalabad, Pakistan; 4Faculty of Pharmacy, Riphah International University, Lahore, PakistanCorrespondence: Muhammad Muzamil KhanThe Islamia University of Bahawalpur, Bahawalpur, Punjab 63100, PakistanEmail muzamilpharmacist@gmail.comAsadullah MadniDepartment of Pharmacy, The Islamia University of Bahawalpur, Bahawalpur, Punjab 63100, PakistanTel +923366248108Email asadpharmacist@hotmail.comBackground: Lipid-polymer hybrid nanoparticles (LPHNP) are suitable for co-delivery of hydrophilic and lipophilic drugs. The structural advantages of polymers and biomimetic properties of lipids enable higher encapsulation of drugs and controlled release profile. Lipid-polymer hybrid nanoparticles have been prepared for co-delivery of curcumin and cisplatin for enhanced cytotoxicity against ovarian cancer.Material and Methods: Chitosan, cisplatin, curcumin, Lipoid S75 were selected as structural components and ionic gelation method was used for preparation of LPHNPs. Nanoparticles were formed via ionic interaction of positively charged chitosan and negatively charged lipid.Results: The optimized nanoparticles were of 225 nm with cationic charge. The encapsulation efficiency was greater than 80% with good drug loading. The drug release profile showed controlled release behavior of both curcumin and cisplatin simultaneously and the absence of burst release. The in vitro therapeutic efficacy and cellular association was evaluated using A2780 ovarian cell lines. To further investigate therapeutic efficacy, we developed 3D spheroids as tumor model to mimic the in vivo conditions. The cytotoxicity and uptake of co-loaded LPHNPs were evaluated on 3D spheroids and results indicated increased chemosensitization and enhanced therapeutic efficacy of co-loaded LPHNPs.Conclusion: Lipid-polymer hybrid nanoparticles could be a suitable platform for co-delivery of curcumin and cisplatin for enhanced cytotoxic effect on ovarian cell lines.Keywords: co-delivery, chemosensitization, curcumin, cisplatin, enhanced therapeutic output

Applications of nanotechnology and material sciences emerge in the development of various novel drug delivery systems that have been proven as promising clinically. Among these, liposomes, noisome, polymeric carriers and lipid-based delivery system were extensively explored and enter into clinical trials and clinical applications. However, each system has its own pros and cons in term of different physicochemical, pharmacokinetics and therapeutics aspects. Lipid-polymer hybrid carriers merge the potential benefit of these structural components and can be prepared by different approaches to improve the therapeutic outcomes. In this chapter, we provide the useful insight about the lipid-polymer hybrid nanoparticles (LPHNPs) that can be prepared by using the different structural components including the synthetic and natural polymers and lipids. Among these, we also explain the various methods to prepare the LPHNPs with various desired characteristics. Finally, the various therapeutic and clinical applications have been presented briefly.