Preparation and Characterization of Copolymeric Polymersomes for Protein Delivery

Abstract

Biodegradable copolymeric polymersomes have been used for controlled drug delivery of proteins. These polymersomes important areas to overcome formulation associated problems of the proteins. The aim of this study was to develop polymersomes using biodegradable copolymers for delivery of bovine serum albumin (BSA) as a model protein. Encapsulated BSA by mPEG-PCL polymersomes led to formation of BSA-loaded mPEG-PCL polymersomes. The polymersomes synthesized with the protein-polymer ratio of 1:4 at 15 000 rpm gave maximum loading, minimum polydispersion with maximally sustained protein release pattern, among the prepared polymersomes. Investigation on FTIR and DSC results revealed that such a high encapsulation efficiency is due to strong interaction between BSA and the copolymer.The particles size and their morphology of polymersomes were determined by DLS and AFM.The encapsulation efficiency of BSA was 91.02%. The results of AFM showed that the polymersomes had spherical shapes with size of 49 nm.The sizes of BSA-loaded polymersomes ranged from 66.06 nm to 84.97 nm. The results showed that polymersomes exhibited a triphasic release, for BSA. Overall, the results indicated that mPEG–PCL polymersomes can be considered as a promising carrier for proteins.

Key words

BSA - copolymers - sustained release - polymrsomes

• References

• 1 Sinha V, Trehan A. Biodegradable microspheres for protein delivery. Journal of controlled release 2003; 90: 261-280
• 2 Dai C, Wang B, Zhao H. Microencapsulation peptide and protein drugs delivery system. Colloids and Surfaces B: Biointerfaces 2005; 41: 117-120
• 3 Ma’mani L, Nikzad S, Kheiri-Manjili H. et al. Curcumin-loaded guanidine functionalized PEGylated I3ad mesoporous silica nanoparticles KIT-6: Practical strategy for the breast cancer therapy. European Journal of Medicinal Chemistry 2014; 83: 646-654
• 4 Manjili HK, Ma’mani L, Tavaddod S. et al. L-Sulforaphane Loaded Fe 3 O 4@ gold core shell nanoparticles: A potential sulforaphane delivery system. PloS one 2016; 11: e0151344
• 5 Al-Musawi S, Naderi-Manesh H, Mohammad Hassan Z. et al. Construction of polyurethane polymeric-based nano-carriers for curcumin in cancer therapy. Modares Journal of Medical Sciences: Pathobiology 2014; 17: 25-39
• 6 Sharafi A, Sohi HH, Mirzaee H. et al. In vitro regeneration and Agrobacterium mediated genetic transformation of Artemisia aucheri Boiss. Physiology and Molecular Biology of Plants 2014; 20: 487-494
• 7 Sharafi A, Sohi HH, Azadi P. et al. Hairy root induction and plant regeneration of medicinal plant Dracocephalum kotschyi. Physiology and Molecular Biology of Plants 2014; 20: 257-262
• 8 Mirzaee H, Sharafi A, Sohi HH. In vitro regeneration and transient expression of recombinant sesquiterpene cyclase (SQC) in Artemisia annua L. South African Journal of Botany 2016; 104: 225-231
• 9 Danafar H. MPEG–PCL copolymeric nanoparticles in drug delivery systems. Cogent Medicine 2016; 3: 1142411
• 10 Muller RH, Keck CM. Challenges and solutions for the delivery of biotech drugs–a review of drug nanocrystal technology and lipid nanoparticles. Journal of biotechnology 2004; 113: 151-170
• 11 Manjili HK, Sharafi A, Danafar H. et al. Poly (caprolactone)–poly (ethylene glycol)–poly (caprolactone)(PCL–PEG–PCL) nanoparticles: A valuable and efficient system for in vitro and in vivo delivery of curcumin. RSC Advances 2016; 6: 14403-14415
• 12 Danafar H, Sharafi A, Kheiri Manjili H. et al. Sulforaphane delivery using mPEG–PCL co-polymer nanoparticles to breast cancer cells. Pharmaceutical Development and Technology 2016; DOI: 10.3109/10837450.2016.1146296.
• 13 Danafar H. Study of the composition of polycaprolactone/poly (ethylene glycol)/polycaprolactone copolymer and drug-to-polymer ratio on drug loading efficiency of curcumin to nanoparticles. Jundishapur J Nat Pharm Prod 2016; DOI: 10.17795/jjnpp-34179.
• 14 Danafar H. Applications of copolymeric nanoparticles in drug delivery systems. Drug Research 2016; 66: 506-519
• 15 Lomas H, Canton I, MacNeil S. et al. Biomimetic pH sensitive polymersomes for efficient DNA encapsulation and delivery. Advanced Materials 2007; 19: 4238-4243
• 16 Pangburn TO, Petersen MA, Waybrant B. et al. Peptide-and aptamer-functionalized nanovectors for targeted delivery of therapeutics. Journal of biomechanical engineering 2009; 131: 074005
• 17 Sharafi A, Sohi HH, Mousavi A. et al. Enhanced morphinan alkaloid production in hairy root cultures of Papaver bracteatum by over-expression of salutaridinol 7-o-acetyltransferase gene via Agrobacterium rhizogenes mediated transformation. World Journal of Microbiology and Biotechnology 2013; 29: 2125-2131
• 18 Manjili HK, Ghasemi P, Malvandi H. et al. Pharmacokinetics and in vivo delivery of curcumin by copolymericmPEG-PCL micelles. Eur J Pharm Biopharm 2016; [Epub ahead ofprint] DOI: 10.1016/j.ejpb.2016.10.003.
• 19 Kim KT, Meeuwissen SA, Nolte RJ. et al. Smart nanocontainers and nanoreactors. Nanoscale 2010; 2: 844-858
• 20 Danafar H, Hamidi M. 2015; Simple and sensitive high-performance liquidchromatography (HPLC) method with UV detection for mycophenolicacid assay in human plasma. Application to a bioequivalence study Adv Pharm Bull 5: 563-568.21
• 21 Lomas H, Du J, Canton I. et al. Efficient encapsulation of plasmid dNA in pH-Sensitive PMPC–PDPA polymersomes: Study of the effect of PDPA block length on copolymer–DNA binding affinity. Macromolecular bioscience 2010; 10: 513-530
• 22 Danafar H, Manjili H, Najafi M. 2016; Study of copolymer composition ondrug loading efficiency of enalapril in polymersomes and cytotoxicityof drug loaded nanoparticles. Drug Res 66: 495-504
• 23 Chen W, Meng F, Cheng R. et al. pH-Sensitive degradable polymersomes for triggered release of anticancer drugs: A comparative study with micelles. Journal of controlled release 2010; 142: 40-46
• 24 Panyam J, Labhasetwar V. Biodegradable nanoparticles for drug and gene delivery to cells and tissue. Advanced Drug Delivery Reviews 2003; 55: 329-347
• 25 Mohanraj V, Chen Y. Nanoparticles-a review. Tropical Journal of Pharmaceutical Research 2006; 5: 561-573
• 26 Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Analytical biochemistry 1976; 72: 248-254
• 27 Goldfine AB, Simonson DC, Folli F. et al. Metabolic effects of sodium metavanadate in humans with insulin-dependent and noninsulin-dependent diabetes mellitus in vivo and in vitro studies. The Journal of Clinical Endocrinology & Metabolism 1995; 80: 3311-3320
• 28 Olivier J-C. Drug transport to brain with targeted nanoparticles. NeuroRx 2005; 2: 108-119
• 29 Agnihotri SA, Mallikarjuna NN, Aminabhavi TM. Recent advances on chitosan-based micro-and nanoparticles in drug delivery. Journal of Controlled Release 2004; 100: 5-28
• 30 Kheiri Manjili H, Sharafi A, Attari E. et al. Pharmacokinetics and in vitro and in vivo delivery of sulforaphane by PCL–PEG–PCL copolymeric-based micelles. Artificial Cells, Nanomedicine, and Biotechnology 2017; 1-12 doi:10.1080/21691401.2017.1282501
• 31 Kumari A, Yadav SK, Yadav SC. Biodegradable polymeric nanoparticles based drug delivery systems. Colloids and Surfaces B: Biointerfaces 2010; 75: 1-18
• 32 Manjili HK, Malvandi H, Mousavi MS. et al. 2016; Preparation andphysicochemical characterization of biodegradable mPEG-PCL coreshellmicelles for delivery of artemisinin. Pharm Sci 22: 234-243.33
• 33 Dellian M, Yuan F, Trubetskoy V. et al. Vascular permeability in a human tumour xenograft: molecular charge dependence. British Journal of Cancer 2000; 82: 1513