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Current Pharmaceutical Design


ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Review Article

Lipid Nanoparticles as Carriers for the Treatment of Neurodegeneration Associated with Alzheimer’s Disease and Glaucoma: Present and Future Challenges

Author(s): Elena S. López*, Ana L.L. Machado, Lorena B. Vidal, Roberto González-Pizarro, Amelia D. Silva and Eliana B. Souto

Volume 26, Issue 12, 2020

Page: [1235 - 1250] Pages: 16

DOI: 10.2174/1381612826666200218101231

Price: $65


Glaucoma constitutes the second cause of blindness worldwide and it is considered a neurodegenerative disorder. In this sense, Alzheimer’s disease, which is the most common type of dementia, also causes neurodegeneration. The association between both diseases remains unknown although it has been hypothesised that a possible connection might exist and it will be analysed throughout the review. In this sense, nanoparticulate systems and specially, lipid nanoparticles could be the key for effective neuroprotection. Lipid nanoparticles are the most recent type of drug nanoparticulate systems. These nanoparticles have shown great potential to encapsulate hydrophobic drugs increasing their bioavailability and being able to deliver them to the target tissue. In addition, they have shown great potential for ocular drug delivery. This review explores the most recent strategies employing lipid nanoparticles for AD and glaucoma.

Keywords: Glaucoma, Alzheimer's disease, lipid nanoparticles, solid lipid nanoparticles, nanostructured lipid carriers, glaucoma.

Battaglia L, Serpe L, Foglietta F, et al. Application of lipid nanoparticles to ocular drug delivery. Expert Opin Drug Deliv 2016; 13(12): 1743-57.
[] [PMID: 27291069]
Kim NJ, Harris A, Gerber A, et al. Nanotechnology and glaucoma: a review of the potential implications of glaucoma nanomedicine. Br J Ophthalmol 2014; 98(4): 427-31.
[] [PMID: 24246373]
Bach-Holm D, Kessing SV, Mogensen U, Forman JL, Andersen PK, Kessing LV. Normal tension glaucoma and Alzheimer disease: comorbidity? Acta Ophthalmol 2012; 90(7): 683-5.
[] [PMID: 21332678]
Müller RH, Shegokar R, Keck CM. 20 years of lipid nanoparticles (SLN and NLC): present state of development and industrial applications. Curr Drug Discov Technol 2011; 8(3): 207-27.
[] [PMID: 21291409]
Chang EE, Goldberg JL. Glaucoma 2.0: neuroprotection, neuroregeneration, neuroenhancement. Ophthalmology 2012; 119(5): 979-86.
[] [PMID: 22349567]
Bertaud S, Aragno V, Baudouin C, Labbé A. [Primary open-angle glaucoma]. Rev Med Interne 2019; 40(7): 445-52.
[] [PMID: 30594326]
Pan Y. Rohit V.Natural history of glaucoma. Indian J Ophthalmol 2011; 59(Suppl 1.): S19-23.
Weinreb RN, Aung T, Medeiros FA. The pathophysiology and treatment of glaucoma: a review. JAMA 2014; 311(18): 1901-11.
[] [PMID: 24825645]
Heneka MT, Carson MJ, El Khoury J, et al. Neuroinflammation in Alzheimer’s disease. Lancet Neurol 2015; 14(4): 388-405.
[] [PMID: 25792098]
Sit AJ, Liu JHK. Pathophysiology of glaucoma and continuous measurements of intraocular pressure. Mol Cell Biomech 2009; 6(1): 57-69.
[PMID: 19382536]
Crish SD, Calkins DJ. Neurodegeneration in glaucoma: progression and calcium-dependent intracellular mechanisms. Neuroscience 2011; 176: 1-11.
[] [PMID: 21187126]
Calkins DJ. Critical pathogenic events underlying progression of neurodegeneration in glaucoma. Prog Retin Eye Res 2012; 31(6): 702-19.
[] [PMID: 22871543]
Tezel G. Oxidative stress in glaucomatous neurodegeneration: mechanisms and consequences. Prog Retin Eye Res 2006; 25(5): 490-513.
[] [PMID: 16962364]
Association A. Alzheimer’s disease facts and figures. Alzheimers Dement 2018; 14: 367-429.
Gaugler J, James B, Johnson T, Scholz K, Weuve J. Alzheimer’s disease facts and figures. Alzheimers Dement 2016; 12(4): 459-509.
[] [PMID: 27570871]
Selkoe DJ, Hardy J. The amyloid hypothesis of Alzheimer’s disease at 25 years. EMBO Mol Med 2016; 8(6): 595-608.
[] [PMID: 27025652]
Jack CR Jr, Bennett DA, Blennow K, et al. NIA-AA Research Framework: Toward a biological definition of Alzheimer’s disease. Alzheimers Dement 2018; 14(4): 535-62.
[] [PMID: 29653606]
Hebert LE, Weuve J, Scherr P. Alzheimer disease in the United States (2020-2050) estimated using 2010 census. Neurology 2013; 80(19): 1778-83.
Smale G, Nichols NR, Brady DR, Finch CE, Horton WE Jr. Evidence for apoptotic cell death in Alzheimer’s disease. Exp Neurol 1995; 133(2): 225-30.
[] [PMID: 7544290]
Bastard JP, Maachi M, Lagathu C, et al. Recent advances in the relationship between obesity, inflammation, and insulin resistance. Eur Cytokine Netw 2006; 17(1): 4-12.
[PMID: 16613757]
Cheignon C, Tomas M, Bonnefont-Rousselot D, Faller P, Hureau C, Collin F. Oxidative stress and the amyloid beta peptide in Alzheimer’s disease. In:Redox Biol 2018; 14: 450-64.
Wostyn P, Audenaert K, De Deyn PP. Alzheimer’s disease and glaucoma: is there a causal relationship? Br J Ophthalmol 2009; 93(12): 1557-9.
[] [PMID: 19286688]
Hinton DR, Sadun AA, Blanks JC, Miller CA. Optic-nerve degeneration in Alzheimer’s disease. N Engl J Med 1986; 315(8): 485-7.
[] [PMID: 3736630]
Blanks JC, Torigoe Y, Hinton DR, Blanks RHI. Retinal pathology in Alzheimer’s disease. I. Ganglion cell loss in foveal/parafoveal retina. Neurobiol Aging 1996; 17(3): 377-84.
[] [PMID: 8725899]
Yoneda S, Hara H, Hirata A, Fukushima M, Inomata Y, Tanihara H. Vitreous fluid levels of β-amyloid((1-42)) and tau in patients with retinal diseases. Jpn J Ophthalmol 2005; 49(2): 106-8.
[] [PMID: 15838725]
McKinnon SJ. Glaucoma: ocular Alzheimer’s disease? Front Biosci 2003; 8: s1140-56.
[] [PMID: 12957857]
LeBlanc A. Increased production of 4 kDa amyloid β peptide in serum deprived human primary neuron cultures: possible involvement of apoptosis. J Neurosci 1995; 15(12): 7837-46.
[] [PMID: 8613723]
Laferla FM, Tinkle B, Bieberich CJ, Haudenschild CC. The Alzheimer’s Abeta peptide nduces neurodegeneration transgenic mice. Nature 1995; 9: 21-30.
[PMID: 7704018]
McKinnon SJ, Lehman DM, Kerrigan-Baumrind LA, et al. Caspase activation and amyloid precursor protein cleavage in rat ocular hypertension. Invest Ophthalmol Vis Sci 2002; 43(4): 1077-87.
[PMID: 11923249]
Gervais FG, Xu D, Robertson GS, et al. Involvement of caspases in proteolytic cleavage of Alzheimer’s amyloid-beta precursor protein and amyloidogenic A beta peptide formation. Cell 1999; 97(3): 395-406.
[] [PMID: 10319819]
Gonzalez-Pizarro R, Silva-Abreu M, Calpena AC, Egea MA, Espina M, García ML. Development of fluorometholone-loaded PLGA nanoparticles for treatment of inflammatory disorders of anterior and posterior segments of the eye. Int J Pharm 2018; 547(1-2): 338-46.
[] [PMID: 29800741]
Sánchez-López E. et al.New potential strategies for Alzheimer’s disease prevention: pegylated biodegradable dexibuprofen nanospheres administration to APPswe/PS1dE9. Nanomedicine 2017; 13(3): 1171-82.
Sánchez-López E, Egea MA, Cano A, et al. PEGylated PLGA nanospheres optimized by design of experiments for ocular administration of dexibuprofen-in vitro, ex vivo and in vivo characterization. Colloids Surf B Biointerfaces 2016; 145: 241-50.
[] [PMID: 27187188]
Ganesan P, Narayanasamy D. Lipid nanoparticles: different preparation techniques, characterization, hurdles, and strategies for the production of solid lipid nanoparticles and nanostructured lipid carriers for oral drug delivery. Sustain Chem Pharm 2017; 6(May): 37-56.
Sánchez-López E, Espina M, Doktorovova S, Souto EB, García ML. Lipid nanoparticles (SLN, NLC): Overcoming the anatomical and physiological barriers of the eye - Part I - Barriers and determining factors in ocular delivery. Eur J Pharm Biopharm 2017; 110: 70-5.
[] [PMID: 27789358]
Naseri N, Valizadeh H, Zakeri-Milani P. Solid lipid nanoparticles and nanostructured lipid carriers: structure preparation and application. Adv Pharm Bull 2015; 5(3): 305-13.
[] [PMID: 26504751]
Shishir MRI, Xie L, Sun C, Zheng X, Chen W. Advances in micro and nano-encapsulation of bioactive compounds using biopolymer and lipid-based transporters. Trends Food Sci Technol 2018; 78: 34-60.
Gonzalez-Mira E, Nikolić S, Calpena AC, Egea MA, Souto EB, García ML. Improved and safe transcorneal delivery of flurbiprofen by NLC and NLC-based hydrogels. J Pharm Sci 2012; 101(2): 707-25.
[] [PMID: 22012873]
Souto EB, Doktorovova S, Gonzalez-Mira E, Egea MA, Garcia ML. Feasibility of lipid nanoparticles for ocular delivery of anti-inflammatory drugs. Curr Eye Res 2010; 35(7): 537-52.
[] [PMID: 20597640]
Bhatta RS, Chandasana H, Chhonker YS, et al. Mucoadhesive nanoparticles for prolonged ocular delivery of natamycin: In vitro and pharmacokinetics studies. Int J Pharm 2012; 432(1-2): 105-12.
[] [PMID: 22569234]
Kels BD, Grzybowski A, Grant-Kels JM. Human ocular anatomy. Clin Dermatol 2015; 33(2): 140-6.
[] [PMID: 25704934]
Liu D, Lian Y, Fang Q, Liu L, Zhang J, Li J. Hyaluronic-acid-modified lipid-polymer hybrid nanoparticles as an efficient ocular delivery platform for moxifloxacin hydrochloride. Int J Biol Macromol 2018; 116: 1026-36.
[] [PMID: 29778883]
Wang F, Chen L, Jiang S, et al. Optimization of methazolamide-loaded solid lipid nanoparticles for ophthalmic delivery using Box-Behnken design. J Liposome Res 2014; 24(3): 171-81.
[] [PMID: 24611687]
Cardigos J, Ferreira Q, Crisóstomo S, et al. Nanotechnology-ocular devices for glaucoma treatment: a literature review. Curr Eye Res 2019; 44(2): 111-7.
[] [PMID: 30309248]
Long B. Anatomy of the eyeHandbook of Emergency Ophthalmology 2018; 1-12.
Chirco KR, Sohn EH, Stone EM, Tucker BA, Mullins RF. Structural and molecular changes in the aging choroid: implications for age-related macular degeneration. Eye (Lond) 2017; 31(1): 10-25.
[] [PMID: 27716746]
J. Salazar, Ana I. Ramírez et al. Anatomy of the Human Optic Nerve: Structure and Function INTech Open, vol i, no tourism 2018; 13.
Mangan BG, Al-Yahya K, Chen CT, et al. Retinal pigment epithelial damage, breakdown of the blood-retinal barrier, and retinal inflammation in dogs with primary glaucoma. Vet Ophthalmol 2007; 10(Suppl. 1): 117-24.
[] [PMID: 17973843]
Kaur C, Foulds WS, Ling EA. Blood-retinal barrier in hypoxic ischaemic conditions: basic concepts, clinical features and management. Prog Retin Eye Res 2008; 27(6): 622-47.
[] [PMID: 18940262]
Mannermaa E, Vellonen KS, Urtti A. Drug transport in corneal epithelium and blood-retina barrier: emerging role of transporters in ocular pharmacokinetics. Adv Drug Deliv Rev 2006; 58(11): 1136-63.
[] [PMID: 17081648]
Shah R, Eldridge D, Palombo E, Harding I. Lipid nanoparticles: production, characterization and stability. Ther Drug Monit 2015; 23(4): 305-15.
Muller RH, Mäder K, Gohla S. Solid lipid nanoparticles (SLN) for controlled drug delivery - a review of the state of the art. Eur J Pharm Biopharm 2000; 50: 161-77.
Ekambaram P, Sathali AH, Priyanka K. A review on solid lipid nanoparticles. Sci Revs Chem Commun 2012; 2(1): 80-102.
Yadav N, Khatak S, Singh Sara UV. Solid lipid nanoparticles- A review. Int J Appl Pharm 2013; 5(2): 8-18.
Garud A, Singh D, Garud N. Solid Lipid Nanoparticles (SLN): method, characterization and applications. Int Curr Pharm J 2012; 1(11): 384-93.
Ramteke KHS. Joshi, and S. Dhole, “Solid lipid nanoparticles- A review. IOSR J Pharm 2012; 2(6): 34-44.
Beloqui A, Solinís MÁ, Rodríguez-Gascón A, Almeida AJ, Préat V. Nanostructured lipid carriers: Promising drug delivery systems for future clinics. Nanomedicine (Lond) 2016; 12(1): 143-61.
[] [PMID: 26410277]
Schafroth N, Arpagaus C, Jadhav UY, Makne S, Douroumis D. Nano and microparticle engineering of water insoluble drugs using a novel spray-drying process. Colloids Surf B Biointerfaces 2012; 90(1): 8-15.
[] [PMID: 22019455]
Tapeinos C, Battaglini M, Ciofani G. Advances in the design of solid lipid nanoparticles and nanostructured lipid carriers for targeting brain diseases. J Control Release 2017; 264: 306-32.
[] [PMID: 28844756]
Gordillo-Galeano A, Mora-Huertas CE. Solid lipid nanoparticles and nanostructured lipid carriers: A review emphasizing on particle structure and drug release. Eur J Pharm Biopharm 2018; 133: 285-308.
[] [PMID: 30463794]
Attama AA, Reichl S, Müller-Goymann CC. Sustained release and permeation of timolol from surface-modified solid lipid nanoparticles through bioengineered human cornea. Curr Eye Res 2009; 34(8): 698-705.
[] [PMID: 19899997]
Andrés-Guerrero V, Bravo-Osuna I, Pastoriza P, Molina-Martinez R, Herrero-Vanrell IT. Novel technologies for the delivery of ocular therapeutics in glaucoma. J Drug Deliv Sci Technol 2017; 42: 180-6.
El-Salamouni NS, Farid RM, El-Kamel AH, El-Gamal SS. Effect of sterilization on the physical stability of brimonidine-loaded solid lipid nanoparticles and nanostructured lipid carriers. Int J Pharm 2015; 496(2): 976-83.
[] [PMID: 26498372]
Li R, Jiang S, Liu D, et al. A potential new therapeutic system for glaucoma: solid lipid nanoparticles containing methazolamide. J Microencapsul 2011; 28(2): 134-41.
[] [PMID: 21142697]
Wang F, Chen L, Zhang D, et al. Methazolamide-loaded solid lipid nanoparticles modified with low-molecular weight chitosan for the treatment of glaucoma: vitro and vivo study. J Drug Target 2014; 22(9): 849-58.
[] [PMID: 25045926]
Belforte NA, Moreno MC, de Zavalía N, et al. Melatonin: a novel neuroprotectant for the treatment of glaucoma. J Pineal Res 2010; 48(4): 353-64.
[] [PMID: 20374442]
Shukla M, Govitrapong P, Boontem P, Reiter RJ, Satayavivad J. Mechanisms of melatonin in alleviating Alzheimer’s disease. Curr Neuropharmacol 2017; 15(7): 1010-31.
[] [PMID: 28294066]
Dhawan S, Kapil R, Singh B. Formulation development and systematic optimization of solid lipid nanoparticles of quercetin for improved brain delivery. J Pharm Pharmacol 2011; 63(3): 342-51.
[] [PMID: 21749381]
Truong CT. Development and evaluation of Quercetin nanoparticles and hot melt cast films for neuroprotectionMater Sci 2017; 188..
Loureiro A, Cavaco-paulo A. Size controlled protein nanoemulsions for cancer therapyCent Biol Eng 2017; 4710.
Neves AR, Queiroz JF, Reis S. Brain-targeted delivery of resveratrol using solid lipid nanoparticles functionalized with apolipoprotein E. J Nanobiotechnology 2016; 14(1): 27.
[] [PMID: 27061902]
Yusuf M, Khan M, Khan RA, Ahmed B. Biochemical evaluation of brain targeted piperidine solid lipid nanoparticles in an experimentally induced Alzheimer’s disease model. J Drug Target 2013; 21(3): 300-11.
[] [PMID: 23231324]
Sachdeva AK, Misra S, Pal Kaur I, Chopra K. Neuroprotective potential of sesamol and its loaded solid lipid nanoparticles in ICV-STZ-induced cognitive deficits: behavioral and biochemical evidence. Eur J Pharmacol 2015; 747: 132-40.
[] [PMID: 25449035]
Picone P, Bondi ML, Montana G, et al. Ferulic acid inhibits oxidative stress and cell death induced by Ab oligomers: improved delivery by solid lipid nanoparticles. Free Radic Res 2009; 43(11): 1133-45.
[] [PMID: 19863373]
Nazem A, Mansoori GA. Nanotechnology for Alzheimer’s disease detection and treatment. Insciences J 2011; 1(4): 169-93.
Kakkar V, Kaur IP. Evaluating potential of curcumin loaded solid lipid nanoparticles in aluminium induced behavioural, biochemical and histopathological alterations in mice brain. Food Chem Toxicol 2011; 49(11): 2906-13.
[] [PMID: 21889563]
Sánchez-López E, Espina M, Doktorovova S, Souto EBB, García MLL. Lipid nanoparticles (SLN, NLC): Overcoming the anatomical and physiological barriers of the eye - Part II - Ocular drug-loaded lipid nanoparticles. Eur J Pharm Biopharm 2017; 110: 58-69.
[] [PMID: 27789359]
Gao P, Xu H, Ding P, Gao Q, Sun J, Chen D. Controlled release of huperzine A from biodegradable microspheres: In vitro and in vivo studies. Int J Pharm 2007; 330(1-2): 1-5.
[] [PMID: 16987624]
Abu-Amero KK, Kondkar AA, Chalam KV. Resveratrol and ophthalmic diseases. Nutrients 2016; 8(4): 200.
[] [PMID: 27058553]
Anubhav A, Malti A, Gyanendra S, Gaurav K, Shubhini AS. Design and development of resveratrol NLCs and their role in synaptic transmission of acetylcholine in C. elegans model. Curr Drug Ther 2017; 12(2): 134-48.
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.
[] [PMID: 24813112]
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.
[] [PMID: 26133084]
Rajput AP, Butani SB. Resveratrol anchored nanostructured lipid carrier loaded in situ gel via nasal route: Formulation, optimization and in vivo characterization. J Drug Deliv Sci Technol 2019; 51: 214-23.
Rajput A, Bariya A, Allam A, Othman S, Butani SB. In situ nanostructured hydrogel of resveratrol for brain targeting: in vitro-in vivo characterization. Drug Deliv Transl Res 2018; 8(5): 1460-70.
[] [PMID: 29785574]
Kim DSHL, Kim JY, Han Y. Curcuminoids in neurodegenerative diseases. Recent Patents CNS Drug Discov 2012; 7(3): 184-204.
[] [PMID: 22742420]
Davis BM, Pahlitzsch M, Guo L, et al. Topical curcumin nanocarriers are neuroprotective in eye disease. Sci Rep 2018; 8(1): 11066.
[] [PMID: 30038334]
Sadegh Malvajerd S. et al.Brain delivery of Curcumin using solid lipid nanoparticles and nanostructured lipid carriers: preparation, optimization, and pharmacokinetic evaluation. ACS Chem Neurosci 2019; 10(1): 728-39.
Meng F, Asghar S, Gao S, et al. A novel LDL-mimic nanocarrier for the targeted delivery of curcumin into the brain to treat Alzheimer’s disease. Colloids Surf B Biointerfaces 2015; 134: 88-97.
[] [PMID: 26162977]
Zhuang CY, Li N, Wang M, et al. Preparation and characterization of vinpocetine loaded nanostructured lipid carriers (NLC) for improved oral bioavailability. Int J Pharm 2010; 394(1-2): 179-85.
[] [PMID: 20471464]
Park SJ, Kim DH, Kim JM, et al. Mismatch between changes in baicalein-induced memory-related biochemical parameters and behavioral consequences in mouse. Brain Res 2010; 1355: 141-50.
[] [PMID: 20691671]
Do C, Leung C, Chan H L H, Civan M, To C. Baicalein lowers intraocular pressure in gerbils Investig opthalmology Vis Sci 2013; 54(13)
Do C, Leung C, Chan H L H, Civan M, To C. Ocular hypotensice effect of baicalein in Sprague-Dawley rats Investig opthalmology Vis Sci 2014; 55(13): 2891.
Tsai MJ, Wu PC, Huang YB, et al. Baicalein loaded in tocol nanostructured lipid carriers (tocol NLCs) for enhanced stability and brain targeting. Int J Pharm 2012; 423(2): 461-70.
[] [PMID: 22193056]
Cacabelos R, Cacabelos P, Torrellas C, Tellado I, Carril JC. Pharmacogenomics of Alzheimer’s disease: Novel therapeutic strategies for drug development Pharmacogenomics in Drug Discovery and Development. Humana Press, New York, NY,. 2014; pp. 323-556.
Blanco A R, Bondi ML, Cavallaro G, et al. Nanostructured formulations for delivering silibinin and other active ingredients for the treatment of eye diseases 2015. WO2016055976A1.
Azeem A, Anwer MK, Talegaonkar S. Niosomes in sustained and targeted drug delivery: some recent advances. J Drug Target 2009; 17(9): 671-89.
[] [PMID: 19845484]
Kaur H, Dhiman S, Arora S. Niosomes: A novel drug delivery system. Int J Pharm Sci Rev Res 2012; 15(1): 113-20.
Saraswathi TS, Mothilal M, Jaganathan MK. Niosomes as an emerging formulation tool for drug delivery-a review. Int J Appl Pharm 2019; 11(2): 7-15.
Aggarwal D, Kaur IP. Improved pharmacodynamics of timolol maleate from a mucoadhesive niosomal ophthalmic drug delivery system. Int J Pharm 2005; 290(1-2): 155-9.
[] [PMID: 15664141]
Dufes C, Gaillard F, Uchegbu IF, Schätzlein AG, Olivier JC, Muller JM. Glucose-targeted niosomes deliver vasoactive intestinal peptide (VIP) to the brain. Int J Pharm 2004; 285(1-2): 77-85.
[] [PMID: 15488681]
Asharani PV, Lianwu Y, Gong Z, Valiyaveettil S. Comparison of the toxicity of silver, gold and platinum nanoparticles in developing zebrafish embryos. Nanotoxicology 2011; 5(1): 43-54.
[] [PMID: 21417687]
Loureiro JA, Andrade S, Duarte A, et al. Resveratrol and grape extract-loaded solid lipid nanoparticles for the treatment of Alzheimer’s disease. Molecules 2017; 22(2): 1-16.
[] [PMID: 28208831]

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