Sustained-release protamine sulphate-impregnated microspheres may reduce the frequent administration of recombinant interferon α-2b in ovarian cancer: in-vitro characterization.
Parenteral administration of recombinant interferon-α-2b (rINF-α-2b) at a dose of 50×10 IU once a week for 8 weeks is recommended for ovarian cancer. However, short half-life, small therapeutic index and proteolytic degradation cause fluctuations in plasma level and pose barriers in the development of a clinically viable dosage form. Therefore, in the present investigation, fluorescein isothiocynate-tagged rINF-α-2b was loaded into stearic acid (*rINF-α-2b-SMs), pectin (*rINF-α-2b-PMs) and gelatin (*rINF-α-2b-GMs) microspheres. Parameters such as particle size, ζ potential, encapsulation efficiency and in-vitro release were studied to follow the optimization process. The formulation, *rINF-α-2b-GMs of particle size 8.3±2.1 μm with an encapsulation efficiency of 76.0±7.4%, offered 97.4% of *rINF-α-2b release at 288 h. Thus, negatively charged extended-release formulation *rINF-α-2b-GMs was then tethered with a gradient concentration (5-20 mg/ml) of a cationic arginine-rich protein stabilizer, protamine sulphate (Pt). The nanoformulation, *rINF-α-2b-Pt-GMs-15 superimposed with 15 mg/ml of Pt, released 95.0% of *rINF-α-2b at 336 h and was designated as the optimized formulation. The optimized formulation also conserved the primary and secondary structure of *rINF-α-2b as analysed by gel electrophoresis and circular dichroism. Moreover, in-vitro cytotoxicity analysis of SKOV3 cells of the optimized nanoformulation reported significantly (one-way analysis of variance test, P<0.05) lower IC50 (414.3 IU/ml) compared with *rINF-α-2b-GMs (514.3 IU/ml) and pure rINF-α-2b (628.6 IU/ml) at 72 h by offering a prolonged cytotoxic effect. Therefore, *rINF-α-2b-Pt-GMs-15, a promising nanomedicine, warrants further in-depth in-vivo study to scale up the technology for clinical translation.
aDepartment of Pharmaceutics, Chandigarh College of Pharmacy, Mohali, Panjab bDr B.R. Ambedkar Centre for Biomedical Research, University of Delhi, Delhi cUniversity Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India.
Monika
M
Gulia
Shweta
S
Rai
Upendra Kumar
UK
Jain
Om Prakash
OP
Katare
Anju
A
Katyal
Jitender
J
Madan
D000970:Antineoplastic Agents / Q000008:administration & dosage*; D045744:Cell Line, Tumor / Q000187:drug effects; D003692:Delayed-Action Preparations; D005260:Female; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage*; D008863:Microspheres; D053769:Nanocapsules; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D010316:Particle Size; D011479:Protamines / Q000737:chemistry*; D011994:Recombinant Proteins / Q000008:administration & dosage
D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D053769:Nanocapsules; D011479:Protamines; D011994:Recombinant Proteins