Transnasal nimodipine-loaded mucoadhesive nanoliposomes: Preparation and in-vitro evaluation

Nozad Rashid Hussein; Huner Kamal Omer

doi:10.15218/zjms.2019.027

Authors

Nozad Rashid Hussein Department of Pharmaceutics, College of Pharmacy, Hawler Medical University, Erbil, Iraq.
Huner Kamal Omer Department of Pharmaceutics, College of Pharmacy, Hawler Medical University, Erbil, Iraq.

DOI:

https://doi.org/10.15218/zjms.2019.027

Keywords:

Mucoadhesive, Nasal, Nimodipine, Nanoliposome

Abstract

Background and objective: Nimodipineis effective in the treatment of various cerebrovascular impairment, but its clinical potential is limited due to several undesirable characteristics such as low bioavailability which caused by first pass effect in the liver and low aqueous solubility. The main purpose of this study was to prepare nimodipine-loaded nanoliposomes for intranasal delivery and performing in-vitro studies.

Methods: The nimodipine loaded nanoliposome formula was prepared by ethanol-based proliposome method and characterized in term of particle size and size distribution, zeta potential, entrapment efficiency, and permeability studies. In addition, mucoadhesive nanoliposomes loaded nimodipine was prepared using chitosan as a mucoadhesive agent.

Results: The in-vitro studies explored particle size increased (122.48nm±0.002) for chitosan coated formulation after sonication in comparison to non-coated formulations (114.09 nm ± 0.025). Also, the zeta potential was positive for the sonicated chitosan-coated formulation (5.286 mV ±0.341) while for non-coated formulations with chitosan were found to be negative (-1.317 mV ± 0.153). The entrapment efficiency (76.033 % ± 0.094 %) and drug permeability (2.53 μg/ml in the duration of 240 min) were significant for chitosan-coated liposome compared to other formulations.

Conclusion: This study concludes that chitosan glutamate (PROTASAN^® UPG213)coatednimodipine-loaded liposomes can be considered as a promising novel formulation for an efficient intranasal delivery of nimodipine. Additionally, changes in the size of liposomes and zeta potential confirmed the existence of a coating layer on the surface of liposome pellets. Chitosan was found to significantly enhance the drug entrapment and could also be considered as a permeability enhancer.

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References

Choudhary R, Goswami L. Nasal route: A novelistic approach for targeted drug delivery to CNS. Int Res J Pharm 2013; 4:59–62.

Illum L. Nasal drug delivery: new developments and strategies. Drug Discov Today 2002; 7(23):1184–9.

Upadhyay P, Trivedi J, Pundarikakshudu K, Sheth N. Direct and enhanced delivery of nanoliposomes of anti schizophrenic agent to the brain through nasal route. Saudi Pharm J SPJ 2017; 25(3):346–58.

Chen KH, Di Sabatino M, Albertini B, Passerini N, Kett VL. The effect of polymer coatings on physicochemical properties of spray-dried liposomes for nasal delivery of BSA. Eur J Pharm Sci Off J Eur Fed Pharm Sci 2013; 50(3–4):312–22.

Khan AR, Liu M, Khan MW, Zhai G. Progress in brain targeting drug delivery system by nasal route. J Control Release Off J Control Release Soc 2017; 268:364–89.

Patil SB, Sawant KK. Development, optimization and in vitro evaluation of alginate mucoadhesive microspheres of carvedilol for nasal delivery. J Microencapsul 2009; 26(5):432–43.

Ugwoke MI, Agu RU, Verbeke N, Kinget R. Nasal mucoadhesive drug delivery: background, applications, trends and future perspectives. Adv Drug Deliv Rev 2005;57(11):1640–65.

Amin M, Jaafari MR, Tafaghodi M. Impact of chitosan coating of anionic liposomes on clearance rate, mucosal and systemic immune responses following nasal administration in rabbits. Colloids Surf B Biointerfaces 2009; 74(1):225–9.

Bonferoni MC, Giunchedi P, Scalia S, Rossi S, Sandri G, Caramella C. Chitosan gels for the vaginal delivery of lactic acid: Relevance of formulation parameters to mucoadhesion and release mechanisms. AAPS Pharm Sci Tech 2006; 7(4):E141–7.

Luppi B, Bigucci F, Cerchiara T, Zecchi V. Chitosan-based hydrogels for nasal drug delivery: from inserts to nanoparticles. Expert Opin Drug Deliv 2010; 7(7):811–28.

Wang Z, Deng Y, Zhang X, Wang T, Wu F. Development and pharmacokinetics of nimodipine-loaded liposomes. J Pharm Pharmacol 2006; 58(9):1289–94.

Song X, Jiang Y, Ren C, Sun X, Zhang Q, Gong T, et al. Nimodipine-loaded mixed micelles: formulation, compatibility, pharmacokinetics, and vascular irritability study. Int J Nanomedicine 2012; 7:3689–99.

Tomassoni D, Lanari A, Silvestrelli G, Traini E, Amenta F. Nimodipine and its use in cerebrovascular disease: evidence from recent preclinical and controlled clinical studies. Clin Exp Hypertens 2008; 30(8):744–66.

Soliman GM, Sharma R, Choi AO, Varshney SK, Winnik FM, Kakkar AK, et al. Tailoring the efficacy of nimodipine drug delivery using nanocarriers based on A2B miktoarm star polymers. Biomaterials 2010; 31(32):8382–92.

Yang D, Zhu J, Zheng Y, Ge L. Preparation, Characterization, and Pharmacokinetics of Sterically Stabilized Nimodipine-Containing Liposomes. Drug Dev Ind Pharm 2006; 32(2):219–27.

Elhissi AMA, Karnam KK, Danesh-Azari M-R, Gill HS, Taylor KMG. Formulations generated from ethanol-based proliposomes for delivery via medical nebulizers. J Pharm Pharmacol 2006; 58(7):887–94.

Schroeder A, Kost J, Barenholz Y. Ultrasound, liposomes, and drug delivery: principles for using ultrasound to control the release of drugs from liposomes. Chem Phys Lipids 2009; 162(1):1–16.

Gavini E, Hegge AB, Rassu G, Sanna V, Testa C, Pirisino G, et al. Nasal administration of carbamazepine using chitosan microspheres: in vitro/in vivo studies. Int J Pharm 2006; 307(1):9–15.

Jaafar-Maalej C, Diab R, Andrieu V, Elaissari A, Fessi H. Ethanol injection method for hydrophilic and lipophilic drug-loaded liposome preparation. J Liposome Res 2010; 20(3):228–43.

Nii T, Ishii F. Encapsulation efficiency of water-soluble and insoluble drugs in liposomes prepared by the microencapsulation vesicle method. Int J Pharm 2005; 298(1):198–205.

Zhang H, Zhu X, Shen J, Xu H, Ma M, Gu W, et al. Characterization of a liposome-based artificial skin membrane for in vitro permeation studies using Franz diffusion cell device. J Liposome Res 2016; 27:1–34.

Shang X, Ma S, Li Z. Development and Validation of a RP-HPLC method for determination of nimodipine in sustained release tablets. Journal of Chemistry 2013; 2013:612082.

Guo J, Ping Q, Jiang G, Huang L, Tong Y. Chitosan-coated liposomes: characterization and interaction with leuprolide. Int J Pharm 2003; 260(2):167–73.

Mady MM, Darwish MM. Effect of chitosan coating on the characteristics of DPPC liposomes. J Adv Res 2010; 1(3):187–91.

Liang X, Mao G, Ng KYS. Mechanical properties and stability measurement of cholesterol-containing liposome on mica by atomic force microscopy. J Colloid Interface Sci 2004; 278(1):53–62.

Nie Y, Ji L, Ding H, Xie L, Li L, He B, et al. Cholesterol derivatives based charged liposomes for doxorubicin delivery: preparation, in vitro and in vivo characterization. Theranostics 2012; 2(11):1092–103.

Paolino D, Sinha P, Fresta M, Mauro F. Drug Delivery Systems - Encyclopedia of Medical Devices and Instrumentation - Paolino - Wiley Online Library; 2006.

Khatri K, Goyal AK, Gupta PN, Mishra N, Mehta A, Vyas SP. Surface modified liposomes for nasal delivery of DNA vaccine. Vaccine 2008; 26(18):2225–33.

Szcześ A. Effects of DPPC/Cholesterol liposomes on the properties of freshly precipitated calcium carbonate. Colloids Surf B Biointerfaces 2013; 101:44–8.

Singla AK, Sharma ML, Dhawan S. Nifedipine loaded chitosan microspheres: characterization of internal structure. Biotech Histochem Off Publ Biol Stain Comm 2001; 76(4):165–71.

Sinha V, Singla A, Wadhawan S, Kaushik R, Kumria R, Bansal K, et al. Chitosan microspheres as a potential carrier for drugs. Int J Pharm 2004; 274(1–2):1–33.

Akbarzadeh A, Rezaei-Sadabady R, Davaran S, Joo SW, Zarghami N, Hanifehpour Y, et al. Liposome: classification, preparation, and applications. Nanoscale Res Lett 2013; 8(1):102.

Ahmed TA, Aljaeid BM. Preparation, characterization, and potential application of chitosan, chitosan derivatives, and chitosan metal nanoparticles in pharmaceutical drug delivery. Drug Des Devel Ther 2016; 10:483–507.

Sonaje K, Chuang E-Y, Lin K-J, Yen T-C, Su F-Y, Tseng MT, et al. Opening of epithelial tight junctions and enhancement of paracellular permeation by chitosan: microscopic, ultrastructural, and computed-tomographic observations. Mol Pharm 2012; 9(5):1271–9.