Intranasal Lipid Particulate Drug Delivery Systems: An Update on Clinical Challenges and Biodistribution Studies of Cerebroactive Drugs in Alzheimer’s disease

Page: [3281 - 3299] Pages: 19

  • * (Excluding Mailing and Handling)

Abstract

Background: Alzheimer's is the primary cause of death in the various countries that affect wide strata of the population. The treatment of it is restricted to a few conventional oral medications that act only superficially. It is evident that the delivery of a drug to the brain across the blood-brain barrier is challenging as the BBB is armed with several efflux transporters like the P-glycoprotein as well as nasal mucociliary clearance adds up leading to decreased concentration and reduced therapeutic efficacy. Considering these, the intranasal IN route of drug administration is emerging as an alternative route for the systemic delivery of a drug to the brain. The intranasal (IN) administration of lipid nanoparticles loaded with cerebroactive drugs showed promise in treating various neurodegenerative diseases, since the nasal route allows the direct nose to brain delivery by means of solid lipid nanoparticles (SLN’s). The tailoring of intranasal lipid particulate drug delivery systems is a pleasing approach to facilitate uptake of therapeutic agents at the desired site of action, particularly when a free drug has poor pharmacokinetics/ biodistribution (PK/BD) or significant off-site toxicities.

Objectives: 1) In this review, key challenges and physiological mechanisms regulating intranasal brain delivery in Alzheimer’s disease, ex vivo studies, pharmacokinetics parameters including brain uptake and histopathological studies are thoroughly discussed.

2) A thorough understanding of the in vivo behaviour of the intranasal drug carriers will be the elusive goal.

3) The article emphasizes to drag the attention of the research community working in the intranasal field towards the challenges and hurdles of the practical applicability of intranasal delivery of cerebroactive drugs.

Method: Various electronic databases, journals like nanotechnology and nanoscience, dove press are reviewed for the collection and compilation of data.

Results: From in vivo biodistribution studies, pharmacokinetics parameters, and gamma scintigraphy images of various drugs, it is speculated that intranasal lipid particulates drug delivery system shows better brain targeting efficiency for various CNS disorders in comparison to other routes.

Conclusion: Various routes are explored for the delivery of drugs to increase bioavailability in the brain for CNS disorders but the intranasal route shows better results that pave the way for success in the future if properly explored.

Keywords: Intranasal, clinical, Alzheimer, bio-distribution, histopathology, lipid carriers.

[1]
Robert A, Freitas Jr. the ad protocols: a nanorobotic cure for ad and related neurodegenerative conditions. 2016.IMM Report no. 48..
[2]
Dementia Fact sheet. World Health Organization 2017.Available at. https://www.who.int/health-topics/dementia#tab=tab_1
[3]
Morrison Ann S. The pathophysiology of AD disease and directions in treatment Advanced studies in nursing 2011; 3(8): 256-70.
[4]
Parihar MS, Hemnani T. Alzheimer’s disease pathogenesis and therapeutic interventions. J Clin Neurosci 2004; 11(5): 456-67.
[http://dx.doi.org/10.1016/j.jocn.2003.12.007] [PMID: 15177383]
[5]
Agrawal M, Saraf S, Saraf S, et al. Nose-to-brain drug delivery: An update on clinical challenges and progress towards approval of anti-Alzheimer drugs. J Control Release 2018; 281: 139-77.
[http://dx.doi.org/10.1016/j.jconrel.2018.05.011] [PMID: 29772289]
[6]
Lin CH, Chen CH, Lin ZC, et al. Recent advances in oral delivery of drugs and bioactive natural products using SLN’s as the carriers. Yao Wu Shi Pin Fen Xi 2017; 25(2): 219-34.
[PMID: 28911663]
[7]
Pardeshi C, Rajput P, Belgamwar V, et al. Solid lipid based nanocarriers: an overview. Acta Pharm 2012; 62(4): 433-72.
[http://dx.doi.org/10.2478/v10007-012-0040-z] [PMID: 23333884]
[8]
Ramteke KH, Joshi SA, Dhole SN. Solid Lipid Nanoparticle: A Review. IOSR Journal of Pharmacy 2012; 2(6): 34-44.
[http://dx.doi.org/10.9790/3013-26103444]
[9]
Bhattacharjee Y. A SLN’s technology as a novel platform for delivery of drugs. Indo Am J Pharm Res 2013; 3: 4079-97.
[10]
Li H. SLN’s technology as a novel platform for delivery of drugs. Cont Release 2009; 133: 238-44.
[http://dx.doi.org/10.1016/j.jconrel.2008.10.002]
[11]
Melike U, Gulgun Y. Importance of SLN’s (SLN) in various administration routes and future perspectives. Int J Nanomedicine 2007; 2(3): 289-300.
[PMID: 18019829]
[12]
Stützle M, Flamm J, Carle S, et al. Nose-to-Brain delivery of insulin for AD. ADMET DMPK 2015; 3: 190-202.
[http://dx.doi.org/10.5599/admet.3.3.184]
[13]
Buchner K, Seitz-Tutter D, Schönitzer K, Weiss DG. A quantitative study of anterograde and retrograde axonal transport of exogenous proteins in olfactory nerve C-fibers. Neuroscience 1987; 22(2): 697-707.
[http://dx.doi.org/10.1016/0306-4522(87)90366-6] [PMID: 3670606]
[14]
Wu H, Hu K, Jiang X. From nose to brain: understanding transport capacity and transport rate of drugs. Expert Opin Drug Deliv 2008; 5(10): 1159-68.
[http://dx.doi.org/10.1517/17425247.5.10.1159] [PMID: 18817519]
[15]
Pardeshi CV, Belgamwar VS. Direct nose to brain drug delivery via integrated nerve pathways bypassing the blood-brain barrier: an excellent platform for brain targeting. Expert Opin Drug Deliv 2013; 10(7): 957-72.
[http://dx.doi.org/10.1517/17425247.2013.790887] [PMID: 23586809]
[16]
Bahadur S, Pathak K. Physicochemical and physiological considerations for efficient nose-to-brain targeting. Expert Opin Drug Deliv 2012; 9(1): 19-31.
[http://dx.doi.org/10.1517/17425247.2012.636801] [PMID: 22171740]
[17]
Areosa SA, Sherriff F. Memantine for dementia. Cochrane Database Syst Rev 2003; 20: 154-60.
[18]
Xie Z, Liao Q, Xu X, Yao M, Wan J, Liu D. Rapid and sensitive determination of donepezil in human plasma by liquid chromatography/tandem mass spectrometry: application to a pharmacokinetic study. Rapid Commun Mass Spectrom 2006; 20(21): 3193-8.
[http://dx.doi.org/10.1002/rcm.2718] [PMID: 17016805]
[19]
Christodoulou C, Melville P, Scherl WF, Macallister WS, Elkins LE, Krupp LB. Effects of donepezil on memory and cognition in multiple sclerosis. J Neurol Sci 2006; 245(1-2): 127-36.
[http://dx.doi.org/10.1016/j.jns.2005.08.021] [PMID: 16626752]
[20]
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(1-2): 300-10.
[http://dx.doi.org/10.1016/j.ijpharm.2013.04.084] [PMID: 23684658]
[21]
Yasir M, Sara UV, Chauhan I, Gaur PK, Singh AP, Puri D. Ameeduzzafar. Solid lipid nanoparticles for nose 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.
[22]
Jain R, Nabar S, Dandekar P, Patravale V. Micellar nanocarriers: potential nose-to-brain delivery of zolmitriptan as novel migraine therapy. Pharm Res 2010; 27(4): 655-64.
[http://dx.doi.org/10.1007/s11095-009-0041-x] [PMID: 20151180]
[23]
Sussman N. Choosing an atypical antipsychotic. Int Clin Psychopharmacol 2002; 17(3)(Suppl. 3): S29-33.
[PMID: 12570069]
[24]
Wang JS, Ruan Y, Taylor RM, Donovan JL, Markowitz JS, DeVane CL. The brain entry of risperidone and 9-hydroxyrisperidone is greatly limited by P-glycoprotein. Int J Neuropsychopharmacol 2004; 7(4): 415-9.
[http://dx.doi.org/10.1017/S1461145704004390] [PMID: 15683552]
[25]
Mistry A, Stolnik S, Illum L. Nanoparticles for direct nose-to-brain delivery of drugs. Int J Pharm 2009; 379(1): 146-57.
[http://dx.doi.org/10.1016/j.ijpharm.2009.06.019] [PMID: 19555750]
[26]
Doijad RC, Manvi FV, Godhwani DM, et al. Formulation and targeting efficiency of cisplatin engineered SLN’s. Indian J Pharm Sci 2008; 70(2): 203.
[http://dx.doi.org/10.4103/0250-474X.41456] [PMID: 20046713]
[27]
Mehnert W, Mäder K. SLN’s: production, characterization and applications. Adv Drug Deliv Rev 2001; 47: 165-96.
[http://dx.doi.org/10.1016/S0169-409X(01)00105-3] [PMID: 11311991]
[28]
Souto EB, Mehnert W, Müller RH. Polymorphic behaviour of Compritol888 ATO as bulk lipid and as SLN and NLC. J Microencapsul 2006; 23(4): 417-33.
[http://dx.doi.org/10.1080/02652040600612439] [PMID: 16854817]
[29]
Singh AP, Saraf SK, Saraf SA. SLN approach for nose-to-brain delivery of alprazolam. Drug Deliv Transl Res 2012; 2(6): 498-507.
[http://dx.doi.org/10.1007/s13346-012-0110-2] [PMID: 25787328]
[30]
Pietrowsky R, Thiemann A, Kern W, Fehm HL, Born J. A nose-brain pathway for psychotropic peptides: evidence from a brain evoked potential study with cholecystokinin. Psychoneuroendocrinology 1996; 21(6): 559-72.
[http://dx.doi.org/10.1016/S0306-4530(96)00012-1] [PMID: 8983091]
[31]
Koziara JM, Lockman PR, Allen DD, Mumper RJ. In situ blood-brain barrier transport of nanoparticles. Pharm Res 2003; 20(11): 1772-8.
[http://dx.doi.org/10.1023/B:PHAM.0000003374.58641.62] [PMID: 14661921]
[32]
Patel S, Chavhan S, Soni H, Babbar A, et al. Brain targeting of risperidone-loaded SLN’s by IN route. J Drug Target 2011; 19(6): 468-74.
[http://dx.doi.org/10.3109/1061186X.2010.523787] [PMID: 20958095]
[33]
Hanafy AS, Farid RM, ElGamal SS. Complexation as an approach to entrap cationic drugs into cationic nanoparticles administered intranasally for Alzheimer’s disease management: preparation and detection in rat brain. Drug Dev Ind Pharm 2015; 41(12): 2055-68.
[http://dx.doi.org/10.3109/03639045.2015.1062897] [PMID: 26133084]
[34]
Rafii MS, Aisen PS. Recent developments in Alzheimer’s disease therapeutics. BMC Med 2009; 7(1): 7.
[http://dx.doi.org/10.1186/1741-7015-7-7] [PMID: 19228370]
[35]
Bala I, Hariharan S, Kumar MR. PLGA nanoparticles in drug delivery: the state of the art crit rev ther drug 2004; 21(5)
[http://dx.doi.org/10.1615/critrevtherdrugcarriersyst.v21.i5.20]
[36]
Fazil M, Md S, Haque S, et al. Development and evaluation of rivastigmine loaded chitosan nanoparticles for brain targeting. Eur J Pharm Sci 2012; 47(1): 6-15.
[http://dx.doi.org/10.1016/j.ejps.2012.04.013] [PMID: 22561106]
[37]
Seju U, Kumar A, Sawant KK. Development and evaluation of olanzapine-loaded PLGA nanoparticles for nose-to-brain delivery: in vitro and in vivo studies. Acta Biomater 2011; 7(12): 4169-76.
[http://dx.doi.org/10.1016/j.actbio.2011.07.025] [PMID: 21839863]
[38]
Muntimadugu E, Dhommati R, Jain A, Challa VG, Shaheen M, Khan W. Intranasal delivery of nanoparticle encapsulated tarenflurbil: A potential brain targeting strategy for Alzheimer’s disease. Eur J Pharm Sci 2016; 92: 224-34.
[http://dx.doi.org/10.1016/j.ejps.2016.05.012] [PMID: 27185298]
[39]
Barone E, Di Domenico F, Butterfield DA. Statins more than cholesterol lowering agents in Alzheimer disease: their pleiotropic functions as potential therapeutic targets. Biochem Pharmacol 2014; 88(4): 605-16.
[http://dx.doi.org/10.1016/j.bcp.2013.10.030] [PMID: 24231510]
[40]
Martins FP, Gutfilen B, de Souza SA, et al. Monitoring rheumatoid arthritis synovitis with 99mTc-anti-CD3. Br J Radiol 2008; 81(961): 25-9.
[http://dx.doi.org/10.1259/bjr/63780400] [PMID: 18039720]
[41]
Martins FP, Souza SA, Gonçalves RT, Fonseca LM, Gutfilen B. Preliminary results of [99mTc]OKT3 scintigraphy to evaluate acute rejection in renal transplants. Transplant Proc 2004; 36(9): 2664-7.
[http://dx.doi.org/10.1016/j.transproceed.2004.09.085] [PMID: 15621118]
[42]
Lopes FP, de Azevedo MN, Marchiori E, da Fonseca LM, de Souza SA, Gutfilen B. Use of 99mTc-anti-CD3 scintigraphy in the differential diagnosis of rheumatic diseases. Rheumatology (Oxford) 2010; 49(5): 933-9.
[http://dx.doi.org/10.1093/rheumatology/kep471] [PMID: 20129997]
[43]
Jiang Y, Li Y, Liu X. Intranasal delivery: circumventing the iron curtain to treat neurological disorders. Expert Opin Drug Deliv 2015; 12(11): 1717-25.
[http://dx.doi.org/10.1517/17425247.2015.1065812] [PMID: 26206202]
[44]
Artursson P, Lindmark T, Davis SS, Illum L. Effect of chitosan on the permeability of monolayers of intestinal epithelial cells (Caco-2). Pharm Res 1994; 11(9): 1358-61.
[http://dx.doi.org/10.1023/A:1018967116988] [PMID: 7816770]
[45]
Prego C, García M, Torres D, Alonso MJ. Transmucosal macromolecular drug delivery. J Control Release 2005; 101(1-3): 151-62.
[http://dx.doi.org/10.1016/j.jconrel.2004.07.030] [PMID: 15588901]
[46]
Illum L. Nanoparticulate systems for nasal delivery of drugs: a real improvement over simple systems? J Pharm Sci 2007; 96(3): 473-83.
[http://dx.doi.org/10.1002/jps.20718] [PMID: 17117404]
[47]
Jogani VV, Shah PJ, Mishra P, Mishra AK, Misra AR. Intranasal mucoadhesive microemulsion of tacrine to improve brain targeting. Alzheimer Dis Assoc Disord 2008; 22(2): 116-24.
[http://dx.doi.org/10.1097/WAD.0b013e318157205b] [PMID: 18525282]
[48]
Vllasaliu D, Exposito-Harris R, Heras A, et al. Tight junction modulation by chitosan nanoparticles: comparison with chitosan solution. Int J Pharm 2010; 400(1-2): 183-93.
[http://dx.doi.org/10.1016/j.ijpharm.2010.08.020] [PMID: 20727955]
[49]
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 2013; 50(3-4): 312-22.
[http://dx.doi.org/10.1016/j.ejps.2013.07.006] [PMID: 23876823]
[50]
Clementino A, Batger M, Garrastazu G, et al. The nasal delivery of nanoencapsulated statins - an approach for brain delivery. Int J Nanomedicine 2016; 11: 6575-90.
[http://dx.doi.org/10.2147/IJN.S119033] [PMID: 27994459]
[51]
Ferreira A, Rodrigues M, Fortuna A, et al. Huperzine A from Huperzia serrata: a review of its sources, chemistry, pharmacology and toxicology. Phytochem Rev 2016; 15(1): 51-85.
[http://dx.doi.org/10.1007/s11101-014-9384-y]
[52]
Zhang HY. New insights into huperzine A for the treatment of Alzheimer’s disease. Acta Pharmacol Sin 2012; 33(9): 1170-5.
[http://dx.doi.org/10.1038/aps.2012.128] [PMID: 22941287]
[53]
Yang G, Wang Y, Tian J, et al. Huperzine A for AD: a systematic review and meta-analysis of randomized clinical trials. PLoS One 2013; 8(9)
[http://dx.doi.org/10.1371/journal.pone.0074916]
[54]
Sheng J, Han L, Qin J, et al. N-trimethyl chitosan chloride-coated PLGA nanoparticles overcoming multiple barriers to oral insulin absorption. ACS Appl Mater Interfaces 2015; 7(28): 15430-41.
[http://dx.doi.org/10.1021/acsami.5b03555] [PMID: 26111015]
[55]
Sharma D, Sharma RK, Sharma N, et al. Nose-to-brain delivery of PLGA-diazepam nanoparticles. AAPS PharmSciTech 2015; 16(5): 1108-21.
[http://dx.doi.org/10.1208/s12249-015-0294-0] [PMID: 25698083]
[56]
Yin Y, Chen D, Qiao M, Lu Z, Hu H. Preparation and evaluation of lectin-conjugated PLGA nanoparticles for oral delivery of thymopentin. J Control Release 2006; 116(3): 337-45.
[http://dx.doi.org/10.1016/j.jconrel.2006.09.015] [PMID: 17097180]
[57]
Pawar D, Goyal AK, Mangal S, et al. Evaluation of mucoadhesive PLGA microparticles for nasal immunization. AAPS J 2010; 12(2): 130-7.
[http://dx.doi.org/10.1208/s12248-009-9169-1] [PMID: 20077052]
[58]
Suzuki YA, Lopez V, Lönnerdal B. Mammalian lactoferrin receptors: structure and function. Cell Mol Life Sci 2005; 62(22): 2560-75.
[http://dx.doi.org/10.1007/s00018-005-5371-1] [PMID: 16261254]
[59]
Liu Z, Jiang M, Kang T, et al. Lactoferrin-modified PEG-co-PCL nanoparticles for enhanced brain delivery of NAP peptide following intranasal administration. Biomaterials 2013; 34(15): 3870-81.
[http://dx.doi.org/10.1016/j.biomaterials.2013.02.003] [PMID: 23453061]
[60]
Critchley H, Davis SS, Farraj NF, Illum L. Nasal absorption of desmopressin in rats and sheep. Effect of a bioadhesive microsphere delivery system. J Pharm Pharmacol 1994; 46(8): 651-6.
[http://dx.doi.org/10.1111/j.2042-7158.1994.tb03876.x] [PMID: 7815278]
[61]
Kumar M, Pandey RS, Patra KC, et al. Evaluation of neuropeptide loaded trimethyl chitosan nanoparticles for nose to brain delivery. Int J Biol Macromol 2013; 61: 189-95.
[http://dx.doi.org/10.1016/j.ijbiomac.2013.06.041] [PMID: 23831532]
[62]
Muntimadugu E, Dhommati R, Jain A, Challa VG, Shaheen M, Khan W. Intranasal delivery of nanoparticle encapsulated Tarenflurbil:A potential brain targeting strategy for AD Eur J Pharm Sci 224-34.
[63]
Meng Q, Wang A, Hua H, et al. Intranasal delivery of Huperzine A to the brain using lactoferrin-conjugated N-trimethylated chitosan surface-modified PLGA nanoparticles for treatment of Alzheimer’s disease. Int J Nanomedicine 2018; 13: 705-18.
[http://dx.doi.org/10.2147/IJN.S151474] [PMID: 29440896]
[64]
Francis PT, Palmer AM, Snape M, Wilcock GK. The cholinergic hypothesis of Alzheimer’s disease: a review of progress. J Neurol Neurosurg Psychiatry 1999; 66(2): 137-47.
[http://dx.doi.org/10.1136/jnnp.66.2.137] [PMID: 10071091]
[65]
Kumar V, Durai NB, Jobe T. Pharmacologic management of Alzheimer’s disease. Clin Geriatr Med 1998; 14(1): 129-46.
[http://dx.doi.org/10.1016/S0749-0690(18)30134-4] [PMID: 9456339]
[66]
McGeer PL, Schulzer M, McGeer EG. Arthritis and anti-inflammatory agents as possible protective factors for Alzheimer’s disease: a review of 17 epidemiologic studies. Neurology 1996; 47(2): 425-32.
[http://dx.doi.org/10.1212/WNL.47.2.425] [PMID: 8757015]
[67]
Calvo P, Remuñan-López C, Vila-Jato JL, Alonso MJ. Chitosan and chitosan/ethylene oxide-propylene oxide block copolymer nanoparticles as novel carriers for proteins and vaccines. Pharm Res 1997; 14(10): 1431-6.
[http://dx.doi.org/10.1023/A:1012128907225] [PMID: 9358557]
[68]
Aktaş Y, Andrieux K, Alonso MJ, et al. Preparation and in vitro evaluation of chitosan nanoparticles containing a caspase inhibitor. Int J Pharm 2005; 298(2): 378-83.
[http://dx.doi.org/10.1016/j.ijpharm.2005.03.027] [PMID: 15893439]
[69]
Al-Ghamdi MS. The anti-inflammatory, analgesic and antipyretic activity of Nigella sativa. J Ethnopharmacol 2001; 76(1): 45-8.
[http://dx.doi.org/10.1016/S0378-8741(01)00216-1] [PMID: 11378280]
[70]
Mansour MA, Nagi MN, El-Khatib AS, Al-Bekairi AM. Effects of thymoquinone on antioxidant enzyme activities, lipid peroxidation and DT-diaphorase in different tissues of mice: a possible mechanism of action. Cell Biochem Funct 2002; 20(2): 143-51.
[http://dx.doi.org/10.1002/cbf.968] [PMID: 11979510]
[71]
Burits M, Bucar F. Antioxidant activity of Nigella sativa essential oil. Phytother Res 2000; 14(5): 323-8.
[http://dx.doi.org/10.1002/1099-1573(200008)14:5<323:AID-PTR621>3.0.CO;2-Q] [PMID: 10925395]
[72]
Zhang Q, Jiang X, Jiang W, Lu W, Su L, Shi Z. Preparation of nimodipine-loaded microemulsion for intranasal delivery and evaluation on the targeting efficiency to the brain. Int J Pharm 2004; 275(1-2): 85-96.
[http://dx.doi.org/10.1016/j.ijpharm.2004.01.039] [PMID: 15081140]
[73]
Vyas TK, Shahiwala A, Marathe S, Misra A. Intranasal drug delivery for brain targeting. Curr Drug Deliv 2005; 2(2): 165-75.
[http://dx.doi.org/10.2174/1567201053586047]
[74]
Wang X, Chi N, Tang X. Preparation of estradiol chitosan nanoparticles for improving nasal absorption and brain targeting. Eur J Pharm Biopharm 2008; 70(3): 735-40.
[http://dx.doi.org/10.1016/j.ejpb.2008.07.005] [PMID: 18684400]
[75]
Alam S, Khan ZI, Mustafa G, et al. Development and evaluation of thymoquinone-encapsulated chitosan nanoparticles for nose-to-brain targeting: a pharmacoscintigraphic study. Int J Nanomedicine 2012; 7: 5705-18.
[http://dx.doi.org/10.2147/IJN.S35329] [PMID: 23180965]
[76]
Millan MJ, Gobert A, Lejeune F, et al. The novel melatonin agonist agomelatine (S20098) is an antagonist at 5-hydroxytryptamine2C receptors, blockade of which enhances the activity of frontocortical dopaminergic and adrenergic pathways. J Pharmacol Exp Ther 2003; 306(3): 954-64.
[http://dx.doi.org/10.1124/jpet.103.051797] [PMID: 12750432]
[77]
Audinot V, Mailliet F, Lahaye-Brasseur C, et al. New selective ligands of human cloned melatonin MT1 and MT2 receptors. Naunyn Schmiedebergs Arch Pharmacol 2003; 367(6): 553-61.
[http://dx.doi.org/10.1007/s00210-003-0751-2] [PMID: 12764576]
[78]
Yous S, Andrieux J, Howell HE, et al. Novel naphthalenic ligands with high affinity for the melatonin receptor. J Med Chem 1992; 35(8): 1484-6.
[http://dx.doi.org/10.1021/jm00086a018] [PMID: 1315395]
[79]
Garcıa-Fuentes M, Torres D, Alonso MJ. Design of lipid nanoparticles for the oral delivery of hydrophilic macromolecules. Colloids Surf B Biointerfaces 2003; 27(2-3): 159-68.
[http://dx.doi.org/10.1016/S0927-7765(02)00053-X]
[80]
CDER U Guidance for industry: estimating the maximum safe starting dose in initial clinical trials for therapeutics in adult healthy volunteers. Rockville, MD: US Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research 2005.
[81]
Romeo VD, deMeireles JC, Gries WJ, et al. Optimization of systemic nasal drug delivery with pharmaceutical excipients. Adv Drug Deliv Rev 1998; 29(1-2): 117-33.
[http://dx.doi.org/10.1016/S0169-409X(97)00064-1] [PMID: 10837583]
[82]
Fatouh AM, Elshafeey AH, Abdelbary A. Intranasal Agomelatine SLN’s to enhance brain delivery: formulation, optimization and in vivo pharmacokinetics. Drug Des Devel Ther 2017; 11: 1815.
[http://dx.doi.org/10.2147/DDDT.S102500] [PMID: 28684900]
[83]
Yasir M, Sara S, Singh UV. SLN’s for N2B delivery of haloperidol: in vitro drug release and pharmacokinetics evaluation. Yao Xue Xue Bao 2014; 4(6): 454-63.
[PMID: 26579417]
[84]
Benvegnú DM, Barcelos RC, Boufleur N, et al. Haloperidol-loaded polysorbate-coated polymeric nanocapsules increase its efficacy in the antipsychotic treatment in rats. Eur J Pharm Biopharm 2011; 77(2): 332-6.
[http://dx.doi.org/10.1016/j.ejpb.2010.12.016] [PMID: 21168486]
[85]
Chen DB, Yang TZ, Lu WL, Zhang Q. In vitro and in vivo study of two types of long-circulating solid lipid nanoparticles containing paclitaxel. Chem Pharm Bull (Tokyo) 2001; 49(11): 1444-7.
[http://dx.doi.org/10.1248/cpb.49.1444] [PMID: 11724235]
[86]
Yasir M, Sara UVS. Preparation and optimization of haloperidol loaded SLN’s by Box-Behnken design. J Pharm Res 2013; 7(6): 551-8.
[http://dx.doi.org/10.1016/j.jopr.2013.05.022]
[87]
Trotta M, Debernardi F, Caputo O. Preparation of solid lipid nanoparticles by a solvent emulsification-diffusion technique. Int J Pharm 2003; 257(1-2): 153-60.
[http://dx.doi.org/10.1016/S0378-5173(03)00135-2] [PMID: 12711170]
[88]
Serralheiro A, Alves G, Fortuna A, Falcão A. Intranasal administration of carbamazepine to mice: a direct delivery pathway for brain targeting. Eur J Pharm Sci 2014; 60: 32-9.
[http://dx.doi.org/10.1016/j.ejps.2014.04.019] [PMID: 24813112]
[89]
Trotta M, Debernardi F, Caputo O. Preparation of SLN’s by a solvent emulsification-diffusion technique. Int J Pharm 2003; 257(1-2): 153-60.
[http://dx.doi.org/10.1016/S0378-5173(03)00135-2] [PMID: 12711170]
[90]
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(1-2): 285-91.
[http://dx.doi.org/10.1016/j.ijpharm.2008.03.029] [PMID: 18455333]
[91]
Jain T, Bhandari A, Ram V, et al. 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): 008-12.
[92]
Rahman N, Khatoon A, Rahman H. Studies on the development of spectrophotometric method for the determination of haloperidol in pharmaceutical preparation. Quim Nova 2012; 35: 392-7.
[http://dx.doi.org/10.1590/S0100-40422012000200028]
[93]
Yasir M, Sara UVS. SLN’s for Nose to Brain delivery of haloperidol: in vitro drug release and pharmacokinetics evaluation. Yao Xue Xue Bao 2014; 4(6): 454-63.
[PMID: 26579417]
[94]
Li JC, Zhang WJ, Zhu JX, et al. Preparation and brain delivery of nasal solid lipid nanoparticles of quetiapine fumarate in situ gel in rat model of schizophrenia. Int J Clin Exp Med 2015; 8(10): 17590-600.
[PMID: 26770349]
[95]
Altamura AC, Moliterno D, Paletta S, et al. Effect of quetiapine and norquetiapine on anxiety and depression in major psychoses using a pharmacokinetic approach: a prospective observational study. Clin Drug Investig 2012; 32(3): 213-9.
[http://dx.doi.org/10.2165/11597330-000000000-00000] [PMID: 22299714]
[96]
Nikisch G, Baumann P, Liu T, Mathé AA. Quetiapine affects neuropeptide Y and corticotropin-releasing hormone in cerebrospinal fluid from schizophrenia patients: relationship to depression and anxiety symptoms and to treatment response. Int J Neuropsychopharmacol 2012; 15(8): 1051-61.
[http://dx.doi.org/10.1017/S1461145711001556] [PMID: 22008251]
[97]
Yu KF. Study of ibuprofen solid lipid nanoparticle in situ gel. Pharmaceutic 2009.
[98]
Qian JJ, Shi SL. Factors affecting drug absorption and improvement measures for nasal in situ gel delivery system. Zhongguo Xin Yao Zazhi 2012; 8: 884-9.
[99]
Niu MM. Study of cyclosporin A solid lipid nanoparticle in situ gel in ocular drugs. Pharmaceutics 2008.
[100]
Li JC, Zhang WJ, Zhu JX, et al. Preparation and brain delivery of nasal SLN’s of quetiapine fumarate in situ gel in a rat model of schizophrenia. Int J Clin Exp Med 2015; 8(10): 17590.
[PMID: 26770349]
[101]
Miki W. Biological functions and activities of animal carotenoids. Pure Appl Chem 63(1): 141-6.
[http://dx.doi.org/10.1351/pac199163010141]
[102]
Prabhu PN, Ashokkumar P, Sudhandiran G. Antioxidative and antiproliferative effects of astaxanthin during the initiation stages of 1,2-dimethyl hydrazine-induced experimental colon carcinogenesis. Fundam Clin Pharmacol 2009; 23(2): 225-34.
[http://dx.doi.org/10.1111/j.1472-8206.2009.00669.x] [PMID: 19645817]
[103]
Tripathi DN, Jena GB. Astaxanthin intervention ameliorates cyclophosphamide-induced oxidative stress, DNA damage and early hepatocarcinogenesis in rat: role of Nrf2, p53, p38 and phase-II enzymes. Mutat Res 2010; 696(1): 69-80.
[http://dx.doi.org/10.1016/j.mrgentox.2009.12.014] [PMID: 20038455]
[104]
Palozza P, Torelli C, Boninsegna A, et al. Growth-inhibitory effects of the astaxanthin-rich alga Haematococcus pluvialis in human colon cancer cells. Cancer Lett 2009; 283(1): 108-17.
[http://dx.doi.org/10.1016/j.canlet.2009.03.031] [PMID: 19423215]
[105]
Gross GJ, Lockwood SF. Acute and chronic administration of disodium disuccinate astaxanthin (Cardax) produces marked cardioprotection in dog hearts. Mol Cell Biochem 2005; 272(1-2): 221-7.
[http://dx.doi.org/10.1007/s11010-005-7555-2] [PMID: 16010990]
[106]
Goodwill KE, Sabatier C, Marks C, Raag R, Fitzpatrick PF, Stevens RC. Crystal structure of tyrosine hydroxylase at 2.3 A and its implications for inherited neurodegenerative diseases. Nat Struct Biol 1997; 4(7): 578-85.
[http://dx.doi.org/10.1038/nsb0797-578] [PMID: 9228951]
[107]
Satoh A, Tsuji S, Okada Y, et al. Preliminary clinical evaluation of toxicity and efficacy of a new astaxanthin-rich Haematococcus pluvialis extract. J Clin Biochem Nutr 2009; 44(3): 280-4.
[http://dx.doi.org/10.3164/jcbn.08-238] [PMID: 19430618]
[108]
Wolf AM, Asoh S, Hiranuma H, et al. Astaxanthin protects mitochondrial redox state and functional integrity against oxidative stress. J Nutr Biochem 2010; 21(5): 381-9.
[http://dx.doi.org/10.1016/j.jnutbio.2009.01.011] [PMID: 19423317]
[109]
Bhatt PC, Srivastava P, Pandey P, et al. Nose to brain delivery of astaxanthin-loaded SLN’s: fabrication, radiolabeling, optimization and biological studies. RSC Advances 2016; 6: 10001-10.
[http://dx.doi.org/10.1039/C5RA19113K]