Glyceryl behenate-based solid lipid nanoparticles as a carrier of haloperidol for nose to brain delivery: formulation development, in-vitro, and in-vivo evaluation
DOI:
https://doi.org/10.1590/s2175-97902022e20254Keywords:
Biodistribution, Brain Targeting, Haloperidol, Nose to brain delivery, ; PharmacokineticAbstract
This study was aimed to develop the haloperidol (HPL) loaded solid lipid nanoparticles (SLNs) for brain targeting through the intranasal route. SLNs were fabricated by the emulsification diffusion technique using glyceryl behenate as lipid and tween 80 as a surfactant. SLNs were evaluated for particle size, zeta potential, structure, entrapment efficiency, solid state characterization by differential scanning calorimetry (DSC), and in-vitro release. In-vivo biological evaluation was performed on albino Wistar rats for the determination of pharmacokinetic as well as brain targeting parameters. Particle size, PDI, zeta potential, and entrapment efficiency of optimized formulation (HPL-SLNs 6) were found to be 103±09 nm, 0.190±0.029, -23.5±1.07 mV, and 79.46±1.97% respectively. In-vitro drug release studies exhibited that 87.21± 3.63% of the entrapped drug was released from the SLNs within 24 h. DSC curves confirmed that during entrapment in SLNs, the drug was solubilized in the lipid matrix and converted into the amorphous form. Enhanced HPL targeting to the brain was observed from HPL-SLNs as compared to HPL-Sol when administered intranasally. The value of AUC 0-∞ in the brain for HPL-SLNs i.n. was found to be nearly 2.7 times higher than that of HPL-Sol i.v., whereas 3.66 times superior to HPL-Sol administered i.n. Stability studies revealed that the formulation remains unchanged when stored at 4±2 °C (refrigerator) and 25±2 °C /60 ±5% RH up to six months. Finally, it could be concluded that SLN is a suitable carrier for HPL with enhanced brain targeting through i.n administration, as compared to the HPL-Sol, administered i.n. and i.v.
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Abdelbary GA, Tadros MI, Brain targeting of olanzapine via intranasal delivery of core shell difunctional block copolymer mixed nanomicellar carriers: In vitro characterization, ex vivo estimation of nasal toxicity and in vivo biodistribution studies. Int J Pharm. 2013;452(2):300- 310.
Alam T, Pandit J, Vohora D, Aqil M, Ali A, Sultana Y. Optimization of nanostructured lipid carriers of lamotrigine for brain delivery: In vitro characterization and in vivo efficacy in epilepsy. Expert Opin Drug Deliv. 2015;12(2)181-94.
Basha SK, Dhandayuthabani R, Muzammil MS, Kumari VS. Solid lipid nanoparticles for oral drug delivery. Mater Today Proc. 2021;36(2):313-324.
Brasnjevic I, Steinbusch C. Schmitz P, Martinez M. Delivery of peptide and protein drugs over the blood-brain barrier. Prog Neurobiol. 2009;87(4):212-251.
Brincat JV, Macleod AD. Haloperidol in palliative care. Palliat Med. 2004;18(3):195-201.
Budhian A, Siegel SJ, Winey KI. Haloperidol-loaded PLGA nanoparticles: systematic study of particle size and drug content. Int J Pharm . 2007;336(2):367-75.
Bunjes H, Unruh T. Characterization of lipid nanoparticles by differential scanning calorimetry, x-ray and neutron scattering. Adv Drug Deliv Rev. 2007;59(6):379-02.
Chadha R, Bhandari S. Drug excipient compatibility screening-role of thermo analytical and spectroscopic techniques. J Pharm Biomed Anal. 2014;87:82-97.
Chang WH, Lam YWF, Jann MW, Chen H. Pharmacokinetics of haloperidol and reduced haloperidol in chinese schizophrenic patients after intravenous and oral administration of haloperidol. Psychopharmacology. 1992;106(4):517-22.
Chen DB, Yang TZ, Zhang O. In vitro and in vivo study of two types of long-circulating solid lipid nanoparticles containing paclitaxel. Chem Pharm Bull. 2001;49(11):1444-7.
Dobrovolskaia MA, Aggarwal P, Hall JB, McNeil SE. Preclinical studies to understand nanoparticle interaction with the immune system and its potential effects on nanoparticle biodistribution. Mol Pharm. 2008;5(4):487-495.
Forsman AO. Individual variability in response to haloperidol. Proc R Soc Med. 1976;69(1):9-13.
Fricker G, Kromp T, Wendel A, Blume A., Zirkel J, Rebmann H, et al. Phospholipids and lipidbased formulations in oral drug delivery. Pharm Res. 2010;27(8):1469-86.
Gastaldi L, Battaglia L, Peira E, Chirio D, Muntoni E, Muntoni L, et al. Solid lipid nanoparticles as vehicles of drugs to the brain: Current state of the art. Eur J Pharm Biopharm. 2014;87(3):433-44.
Gidwani B, Vyas A. Preparation, characterization, and optimization of altretamine-loaded solid lipid nanoparticles using Box-Behnkendesignandresponsesurfacemethodology. Artif Cells Nanomed Biotechnol. 2016;44(2):571-80.
Haque S, Md S, Sahni JK, Ali J, Baboota S. Development and evaluation of brain targeted intranasal alginate nanoparticles for treatment of depression. J Psychiatr Res. 2014;48(1):1-12.
Higuchi T. Mechanism of sustained action medication: theoretical analysis of rate release of solid drug. J Pharm Sci. 1961;50:74-9.
International Conference On Harmonisation of Technical Requirements For Registration of Pharmaceuticals For Human Use, ICH Harmonised Tripartite Guideline: Stability Testing of New Drug Substances and Products, ICH Q1A-R2, 2003.
Jain R, Nabar S, Dandekar P. Micellar nanocarriers: potentialnose-to-brain delivery of zolmitriptan as novel migraine therapy. Pharm Res . 2010;27(4):655-664.
Jain T, Bhandari A, Ram V, Sharma S, Chaudhary RK, Parakh M. High performance liquid chromatographic method with diode array detection for quantification of haloperidol levels in schizophrenic patients during Routine clinical practice. J Bioanal Biomed. 2011;3(1):8-12.
Jann MW, Kennedy WK. Safety and Tolerability of Antipsychotics. In Spina E,Trifirò G, (Eds.). Pharmacovigilance in Psychiatry. Springer International Publishing, Cham, 2016. PP. 167-189.
Jores K, Mehnert W, Drechsler M. Investigations on the structure of solid lipid nanoparticles (SLN) and oil-loaded solid lipid nanoparticles by photon correlation spectroscopy, field-flow fractionation and transmission electron microscopy. J Control Release. 2004;95(2):217-27.
Kanazawa, T, Taki H, Tanaka K, Takashima Y, Okada H. Cell-penetratingpeptide-modified block copolymer micelles promote direct brain delivery via intranasal administration. Pharm Res . 2011;28(9):2130-9.
Korsmeyer RW, Gurny R., Doelker E, Buri P, Pappas NA. Mechanism of solute release from porous hydrophilic polymers. Int J Pharm . 1961;15(2):25-35.
Kumar M, Misra A, Babbar AK, Mishra AK, Mishra P, Pathak K. Intranasal nanoemulsion based brain targeting drug delivery system of risperidone. Int J Pharm . 2008;358(1):285-91.
Pandey R, Sharma S, Khuller GK. Oral solid lipid nanoparticle-based antitubercular chemotherapy. Tuberculosis. 2005;85(5):415-20.
Pandita D, Ahuja A, Velpandian T, Lather V, Dutta T, Khar R.K. Characterization and in vitro assessment of paclitaxel loaded lipid nanoparticles formulated using modified solvent injection technique. Pharmazie. 2009;64(5):301-10.
Patel MN, Lakkadwala S, Majrad MS, Injeti ER, Gollmer SM, Shah ZA, et al. Characterization and Evaluation of 5-Fluorouracil-Loaded Solid Lipid Nanoparticles Prepared via a Temperature-Modulated Solidification Technique. Ageing Int. 2014;15(6):1498-508.
Schwarz C, Mehnert W, Lucks JS, Muller RH. Solid lipid nanoparticles for controlled drug delivery-I. production, characterization and sterilization. J Control Release . 1994;30(1):83-96.
Settle EC, Ayd FJ. Haloperidol: a quarter century of experience. J Clin Psychiatry. 1983;44(12):440-48.
Shah AK, Date AA, Joshi MD, Patravale VB. Solid lipid nanoparticles of tretinoin: potential in topical delivery. Int J Pharm . 2007;345(2):163-71.
Shah. B, Khunt, D, Bhatt H, Misra M, Padh H. Application of quality by design approach for intranasal delivery of rivastigmine loaded solid lipid nanoparticles: Effect on formulation and characterization parameters. Eur J Pharm Sci . 2015;78:54-66.
Singh AP, Saraf SK, Saraf SA. SLN approach for nose-to-brain delivery of alprazolam. Drug Deliv Transl Res. 2012;2(6):498-507.
Soutto EB, Wising SA, Barbosa CM, Muller RH. Development of a controlled released formulation based on SLN and NLC for the topical clotrimazole delivery. Int J Pharm . 2004;278(2):71-7.
Trotta M, Debernardi F, Caputo O. Preparation of solid lipid nanoparticles by a solvent emulsification diffusion technique. Int J Pharm . 2003;257(2):153-60.
Varshosaz J, Tabbakhian M, Mohammadi MY. Formulation and optimization of solid lipid nanoparticles of buspirone HCl for enhancement of its oral bioavailability. J Liposome Res. 2010;20(4):286-96.
Wang F, Jiang X, Lu W. Profiles of methotrexate in blood and CSF following intranasal and intravenous administration to rats. Int J Pharm . 2003;263(2):1-7.
Wang W, Wang C, Zhang Y, Fu H, Gao, Zhang R. Preparation and characterization of solid lipid nanoparticles loaded with salmon calcitonin phospholipid complex. J Drug Deliv Sci Tec. 2019;52:838-45.
Wong HL, Wu XY, Bendayan R. Nanotechnological advances for the delivery of CNS therapeutics, Adv Drug Deliv Rev . 2012;64(7):686-700.
Yasir M, Sara UVS, Chauhan I, Gaur PK, Singh AP, Puri D, et al. Solid lipid nanoparticles fornose to brain delivery of donepezil: formulation, optimization by Box-Behnken design,in vitro and in vivo evaluation. Artif Cells, Nanomed Biotechnol. 2018;46(8):1838-51.
Yasir M, Sara UVS. Development and validation of UV spectrophotometric method for the estimation of haloperidol. Br J Pharm Res . 2014;4(11):1407-15.
Zhang QZ, Jiang XG, Jiang WM, LU W, SU LN, SHI ZQ. Preparation of nimodipine-loaded microemulsion for intranasal delivery and evaluation on the targeting efficiency to the brain. Int J Pharm . 2004;275(2):85-96.
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