Simultaneous delivery of paclitaxel and erlotinib from dual drug loaded PLGA nanoparticles: Formulation development, thorough optimization and in vitro release Tahir Khuroo a, ⁎, Devina Verma a , Arshad Khuroo b , Asgar Ali a, ⁎, Zeenat Iqbal a, ⁎ a Department of Pharmaceutics, SPER, Jamia Hamdard, Hamdard Nagar, New Delhi 110062, India b Department of Clinical Pharmacology and Pharmacokinetics, Sun Pharma, HSIDC, GP-5,Old Delhi Gurgaon Road, Udyog Vihar Industrial Area, Gurgaon 122015, Haryana, India abstract article info Article history: Received 27 December 2017 Received in revised form 16 February 2018 Accepted 21 February 2018 Available online 26 February 2018 The current approach involves the development of dual drug loaded nanoparticles of Paclitaxel (Pac) and Erloti- nib (Erl) with subsequent thorough optimization in order to achieve sustained and simultaneous delivery of Pac and Erl. The formulation is developed to produce maximum efficacy with least side effects. The dual loaded pac- litaxel and erlotinib nanoparticles (PE-NPs) were prepared by modified single emulsion method with appropri- ate optimization. The formulation was optimized for size, polydispersity index (PDI), zeta potential, surface morphology, encapsulation efficiency and loading capacity. The XRD and DSC results of a physical mixture and PE-NPs together confirmed that there was not any physical or chemical interaction among the drugs and polymer (PLGA). Further, the XRD and DSC analyses revealed that the crystalline forms of both drugs in PE-NPs were changed into amorphous form. The optimized PE-NPs were observed to have the particle size of 145.5 ± 3.2 nm, zeta potential of −9.3 ± 1.4 mV and PDI of 0.135 which indicated the particles to be of uniform size with optimum stability. The entrapment efficiency of paclitaxel was found to be 90.36% and that of erlotinib was found to be 62.23% from PE-NPs. PE-NPs further showed the sustained release of drugs from the particles with total release of 65.25% for paclitaxel and 74.83% for erlotinib in 120 h. Accelerated and intermediate stability studies also indicated that there was a minimal variation in size and entrapment efficiency of PE-NPs. © 2018 Published by Elsevier B.V. Keywords: Paclitaxel Erlotinib PLGA nanoparticles in vitro release HPLC-MS/MS 1. Introduction Paclitaxel is among the cytoskeletal drugs that target tubulin. Pacli- taxel causes defects in mitotic and spindle assembly of cells as well as cell division. Paclitaxel is different from other tubulin-targeting drugs such as colchicine which inhibit microtubule assembly; paclitaxel has got the property to stabilize the microtubule polymer and protects it from disassembly which makes chromosomes unable to achieve a metaphase spindle configuration. Thus progression of mitosis is inhibited [1]. Paclitaxel is among the recommended regimens when there is a fail- ure of combination chemotherapy for metastatic breast cancer or if there is a relapse during the 6 months of adjuvant chemotherapy. Only albumin bound nanoparticles of paclitaxel (nab-PTX) has become officially part of the first-line treatment of cancer among the clinically- validated nanomedicines [2]. Erlotinib specifically targets the epidermal growth factor receptor (EGFR) tyrosine kinase, which is highly expressed and occasionally mu- tated in various forms of cancer. Epidermal growth factor receptor (EGFR/HER1) is a member of the ErbB superfamily of type I receptor ty- rosine kinases, which also includes HER2, HER3, and HER4 [3]. The chemotherapy is mostly used in the stage 2–4 of breast cancer. Additionally, breast cancer is often associated with metastases and Pac- litaxel and Erlotinib has been found as efficacious drugs for this purpose. [4]. As reported by [5], anti-angiogenic action of paclitaxel/Erlotinib could be successful means of countering cell proliferation. When multiple drugs are administered separately, each API acts ac- cording to its own distinct pharmacology. Because drugs differ in their pharmacokinetic and pharmacodynamic properties, there is no certi- tude that target cells or tissues will synchronously receive optimal levels of each therapeutic entity. Conversely, when drugs are combined in a single NP carrier, the spatiotemporal exposure of each drug can be con- trolled more precisely and this may translate to a synergistic action among the APIs [2]. Journal of Molecular Liquids 257 (2018) 52–68 Abbreviations: PLGA, Poly lactic acid co glycolic acid; PE-NPs, Paclitaxel and erlotinib dual loaded Nanoparticles; PVA, Poly vinyl alcohol; XRD, X-ray diffraction; DSC, Differential scanning calorimetry; Erl, Erlotinib; Pac, Paclitaxel; OP, Organic phase; EAP, External aqueous phase. ⁎ Corresponding authors. E-mail addresses: tahirkhuroo11@gmail.com (T. Khuroo), aali@jamiahamdard.ac.in (A. Ali), ziqbaljh@yahoo.co.in (Z. Iqbal). https://doi.org/10.1016/j.molliq.2018.02.091 0167-7322/© 2018 Published by Elsevier B.V. Contents lists available at ScienceDirect Journal of Molecular Liquids journal homepage: www.elsevier.com/locate/molliq