title: Stealth lipid coated aquasomes bearing recombinant human interferon-α-2b offered prolonged release and enhanced cytotoxicity in ovarian cancer cells.
abstract: OBJECTIVE
  In present investigation, recombinant human interferon-α-2b (rhINF-α-2b) loaded aquasomes were prepared, optimized and overlaid with PEGylated phospholipid to offer prolong release and high therapeutic index against ovarian cancer, SKOV3 cells.
  
  
  RESULTS
  Central Composite Design (CCD) and Response Surface Methodology (RSM) were employed to calculate the optimized conditions, 1:3 core to coat ratio, sonication power of 12.5W and time of about 55min for preparation of aquasomes. Consequently, rhINF-α-2b-Py-5-P-Aq.somes exhibited higher protein loading capacity and retained structural conformations of rhINF-α-2b, as compared to rhINF-α-2b-Cellob-Aq.somes, rhINF-α-2b-Tre-Aq.somes and rhINF-α-2b-Core (CaHPO4). Further, optimized rhINF-α-2b-Py-5-P-Aq.somes was superimposed with phospholipid-PEG2000 to prolong the release pattern of rhINF-α-2b from aquasomes. The rhINF-α-2b-core (CaHPO4) released 97.3% of protein in 1h, while 95.3% of rhINF-α-2b was released by rhINF-α-2b-Tre-Aq.somes in 4h. Concurrently, rhINF-α-2b-Cellob-Aq.somes and rhINF-α-2b-Py-5-P-Aq.somes released 96.2% and 97.8% of rhINF-α-2b respectively in 6 and 8h. Ultimately, rhINF-α-2b-Py-5-P-Aq.somes-P-PEG2000 displayed evidence of its prolonged release pattern and released 98.1% of rhINF-α-2b in 336h. FT-IR and XRD substantiated the involvement of vigorous intermolecular hydrogen bonding and amorphous geometry in rhINF-α-2b-Py-5-P-Aq.somes. In last, rhINF-α-2b-Py-5-P-Aq.somes-P-PEG2000 exhibited the∼4.55, 1.92, 2.3, 2.8, and 3.84 fold reductions in IC50 as compared to free rhINF-α-2b, rhINF-α-2b-Py-5-P-Aq.somes, rhINF-α-2b-Cellob-Aq.somes, rhINF-α-2b-Tre-Aq.somes and rhINF-α-2b-Core (CaHPO4), respectively.
  
  
  CONCLUSIONS
  Therefore, rhINF-α-2b-Py-5-P-Aq.somes-P-PEG2000 warrant further in depth in vitro and in vivo antitumor study to scale up the technology for clinical intervention.
authors: Department of Pharmaceutics, Chandigarh College of Pharmacy, Mohali (Panjab) India.
authors: Kamaljeet
authors: K
authors: Kaur
authors: Department of Pharmaceutics, Chandigarh College of Pharmacy, Mohali (Panjab) India.
authors: Preeti
authors: P
authors: Kush
authors: SLT Institute of Pharmaceutical Sciences, Guru Ghasidas University, Bilaspur, India.
authors: Ravi Shankar
authors: RS
authors: Pandey
authors: Department of Pharmaceutics, Chandigarh College of Pharmacy, Mohali (Panjab) India. Electronic address: jitenderpharmacy@gmail.com.
authors: Jitender
authors: J
authors: Madan
authors: Department of Pharmaceutics, Chandigarh College of Pharmacy, Mohali (Panjab) India.
authors: Upendra Kumar
authors: UK
authors: Jain
authors: University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India.
authors: Om Prakash
authors: OP
authors: Katare
mesh_terms: D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002942:Circular Dichroism; D003692:Delayed-Action Preparations; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006801:Humans; D020128:Inhibitory Concentration 50; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000494:pharmacology / Q000627:therapeutic use*; D008055:Lipids / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry* / Q000648:ultrastructure; D010051:Ovarian Neoplasms / Q000473:pathology*; D010316:Particle Size; D011994:Recombinant Proteins / Q000494:pharmacology* / Q000627:therapeutic use; D017550:Spectroscopy, Fourier Transform Infrared; D055672:Static Electricity; D013499:Surface Properties; D014961:X-Ray Diffraction
chemical_list: D003692:Delayed-Action Preparations; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D008055:Lipids; D008081:Liposomes; D011994:Recombinant Proteins
keywords: Aquasomes; Cellobiose; Cytotoxicity; Phospholipid-PEG(2000); Pyridoxal-5-phosphate; Trehalose; rhINF-α-2b