Generic placeholder image

Current Drug Delivery

Editor-in-Chief

ISSN (Print): 1567-2018
ISSN (Online): 1875-5704

Research Article

PLGA Nanoparticles for Nose to Brain Delivery of Clonazepam: Formulation, Optimization by 32 Factorial Design, In Vitro and In Vivo Evaluation

Author(s): Pranav Shah*, Jayant Sarolia, Bhavin Vyas, Priti Wagh, Kaul Ankur and Mishra Anil Kumar

Volume 18, Issue 6, 2021

Published on: 07 July, 2020

Page: [805 - 824] Pages: 20

DOI: 10.2174/1567201817666200708115627

Price: $65

Abstract

Background: Intranasal administration of biodegradable nanoparticles has been extensively studied for targeting the drug directly to CNS through the olfactory or trigeminal route bypassing the blood brain barrier.

Objective: The objective of the present study was to optimize Clonazepam loaded PLGA nanoparticles (CLO-PNPs) by investigating the effect of process variables on the responses using 32 full factorial design.

Methods: Effect of two independent factors-amount of PLGA and concentration of Poloxamer 188, were studied at low, medium, and high levels on three dependent responses-%Entrapment efficiency, Particle size (nm), and % cumulative drug release at 24hr.

Results: %EE, Particle size, and %CDR at 24hr of the optimized batch was 63.7%, 165.1 nm, and 86.96%, respectively. Nanoparticles were radiolabeled with 99mTc and biodistribution was investigated in BALB/c mice after intranasal and intravenous administrations. Significantly higher brain/blood uptake ratios and AUC values in the brain following intranasal administration of CLO-PNPs indicated more effective brain targeting of CLO. Higher brain uptake of intranasal CLO-PNPs was confirmed by rabbit brain scintigraphy imaging. A histopathological study performed on goat nasal mucosa revealed no adverse response of nanoparticles. TEM image exhibited spherical shaped particles in the nano range. DSC and XRD studies suggested Clonazepam encapsulation within the PLGA matrix. The onset of occurrence of PTZ-induced seizures in rats was significantly delayed by intranasal nanoparticles as compared to intranasal and intravenous CLO-SOL.

Conclusion: This investigation exhibits rapid rate and higher extent of CLO transport in the brain with intranasal CLO-PNPs suggesting a better option as compared to oral and parenteral route in the management of acute status epilepticus.

Keywords: Clonazepam, Nose-to-brain delivery, biodistribution, 32 factorial design, gamma scintigraphy, nanoparticles.

Graphical Abstract
[1]
Chen, J.W.; Wasterlain, C.G. Status epilepticus: pathophysiology and management in adults. Lancet Neurol., 2006, 5(3), 246-256.
[http://dx.doi.org/10.1016/S1474-4422(06)70374-X] [PMID: 16488380]
[2]
Manno, E.M., Ed.; New management strategies in the treatment of status epilepticus. Mayo Clinic Proceedings; Elsevier, 2003.
[3]
Lockey, A.S. Emergency department drug therapy for status epilepticus in adults. Emerg. Med. J., 2002, 19(2), 96-100.
[http://dx.doi.org/10.1136/emj.19.2.96] [PMID: 11904250]
[4]
Löscher, W.; Ganter, M.; Fassbender, C.P. Correlation between drug and metabolite concentrations in plasma and anesthetic action of ketamine in swine. Am. J. Vet. Res., 1990, 51(3), 391-398.
[PMID: 2316916]
[5]
Han, H.C.; Lee, D.H.; Chung, J.M. Characteristics of ectopic discharges in a rat neuropathic pain model. Pain 2000, 84(2-3), 253-261.
[PMID: 10666530]
[6]
Kapoor, M.; Cloyd, J.C.; Siegel, R.A. A review of intranasal formulations for the treatment of seizure emergencies. J. Control. Release, 2016, 237, 147-159.
[http://dx.doi.org/10.1016/j.jconrel.2016.07.001] [PMID: 27397490]
[7]
Kaminow, L.; Schimschock, J.R.; Hammer, A.E.; Vuong, A. Lamotrigine monotherapy compared with carbamazepine, phenytoin, or valproate monotherapy in patients with epilepsy. Epilepsy Behav., 2003, 4(6), 659-666.
[http://dx.doi.org/10.1016/j.yebeh.2003.08.033] [PMID: 14698699]
[8]
Castel-Branco, M.; Lebre, V.; Falcão, A.; Figueiredo, I.; Caramona, M. Relationship between plasma and brain levels and the anticonvulsant effect of lamotrigine in rats. Eur. J. Pharmacol., 2003, 482(1-3), 163-168.
[http://dx.doi.org/10.1016/j.ejphar.2003.09.065] [PMID: 14660018]
[9]
Graff, C.L.; Pollack, G.M. Nasal drug administration: potential for targeted central nervous system delivery. J. Pharm. Sci., 2005, 94(6), 1187-1195.
[http://dx.doi.org/10.1002/jps.20318] [PMID: 15858850]
[10]
Gulati, N.; Nagaich, U.; Saraf, S.A. Intranasal delivery of chitosan nanoparticles for migraine therapy. Sci. Pharm., 2013, 81(3), 843-854.
[http://dx.doi.org/10.3797/scipharm.1208-18] [PMID: 24106677]
[11]
Al-Ghananeem, A.M.; Saeed, H.; Florence, R.; Yokel, R.A.; Malkawi, A.H. Intranasal drug delivery of didanosine-loaded chitosan nanoparticles for brain targeting; an attractive route against infections caused by AIDS viruses. J. Drug Target., 2010, 18(5), 381-388.
[http://dx.doi.org/10.3109/10611860903483396] [PMID: 20001275]
[12]
Alsarra, I.A.; Hamed, A.Y.; Mahrous, G.M.; El Maghraby, G.M.; Al-Robayan, A.A.; Alanazi, F.K. Mucoadhesive polymeric hydrogels for nasal delivery of acyclovir. Drug Dev. Ind. Pharm., 2009, 35(3), 352-362.
[http://dx.doi.org/10.1080/03639040802360510] [PMID: 18770068]
[13]
Colombo, G.; Lorenzini, L.; Zironi, E.; Galligioni, V.; Sonvico, F.; Balducci, A.G.; Pagliuca, G.; Giuliani, A.; Calzà, L.; Scagliarini, A. Brain distribution of ribavirin after intranasal administration. Antiviral Res., 2011, 92(3), 408-414.
[http://dx.doi.org/10.1016/j.antiviral.2011.09.012] [PMID: 22001322]
[14]
Fazil, M.; Md, S.; Haque, S.; Kumar, M.; Baboota, S.; Sahni, J.K.; Ali, J. 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]
[15]
Seju, U.; Kumar, A.; Sawant, K.K. Development and evaluation of olanzapine-loaded PLGA nanoparticles for nose-to-brain delivery: in vitro and in vivo studies. Acta Biomater., 2011, 7(12), 4169-4176.
[http://dx.doi.org/10.1016/j.actbio.2011.07.025] [PMID: 21839863]
[16]
Eskandari, S.; Varshosaz, J.; Minaiyan, M.; Tabbakhian, M. Brain delivery of valproic acid via intranasal administration of nanostructured lipid carriers: in vivo pharmacodynamic studies using rat electroshock model. Int. J. Nanomedicine, 2011, 6, 363-371.
[PMID: 21499426]
[17]
Misra, A.; Ganesh, S.; Shahiwala, A.; Shah, S.P. Drug delivery to the central nervous system: a review. J. Pharm. Pharm. Sci., 2003, 6(2), 252-273.
[PMID: 12935438]
[18]
Begley, D.J. The blood-brain barrier: principles for targeting peptides and drugs to the central nervous system. J. Pharm. Pharmacol., 1996, 48(2), 136-146.
[http://dx.doi.org/10.1111/j.2042-7158.1996.tb07112.x] [PMID: 8935161]
[19]
Su, Y.; Sinko, P.J. Drug delivery across the blood-brain barrier: why is it difficult? how to measure and improve it? Expert Opin. Drug Deliv., 2006, 3(3), 419-435.
[http://dx.doi.org/10.1517/17425247.3.3.419] [PMID: 16640501]
[20]
Illum, L. Nasal drug delivery--possibilities, problems and solutions. J. Control. Release, 2003, 87(1-3), 187-198.
[http://dx.doi.org/10.1016/S0168-3659(02)00363-2] [PMID: 12618035]
[21]
Pires, A.; Fortuna, A.; Alves, G.; Falcão, A. Intranasal drug delivery: how, why and what for? J. Pharm. Pharm. Sci., 2009, 12(3), 288-311.
[http://dx.doi.org/10.18433/J3NC79] [PMID: 20067706]
[22]
Sperling, M.R.; Haas, K.F.; Krauss, G.; Seif Eddeine, H.; Henney, H.R., III; Rabinowicz, A.L.; Bream, G.; Squillacote, D.; Carrazana, E.J. Dosing feasibility and tolerability of intranasal diazepam in adults with epilepsy. Epilepsia, 2014, 55(10), 1544-1550.
[http://dx.doi.org/10.1111/epi.12755] [PMID: 25154625]
[23]
Djupesland, P.G.; Messina, J.C.; Mahmoud, R.A. The nasal approach to delivering treatment for brain diseases: an anatomic, physiologic, and delivery technology overview. Ther. Deliv., 2014, 5(6), 709-733.
[http://dx.doi.org/10.4155/tde.14.41] [PMID: 25090283]
[24]
Masserini, M. Nanoparticles for brain drug delivery. ISRN Biochem., 2013.
[http://dx.doi.org/10.1155/2013/238428]
[25]
Gizurarson, S. Anatomical and histological factors affecting intranasal drug and vaccine delivery. Curr. Drug Deliv., 2012, 9(6), 566-582.
[http://dx.doi.org/10.2174/156720112803529828] [PMID: 22788696]
[26]
Thorne, R., Ed.; Delivery of insulin-like growth factor-1 to the brain and spinal cord along olfactory and trigeminal pathways following intranasal administration: a noninvasive method for bypassing the blood-brain barrier; Soc Neurosci Abstracts, 2000.
[27]
Westin, U.E.; Boström, E.; Gråsjö, J.; Hammarlund-Udenaes, M.; Björk, E. Direct nose-to-brain transfer of morphine after nasal administration to rats. Pharm. Res., 2006, 23(3), 565-572.
[http://dx.doi.org/10.1007/s11095-006-9534-z] [PMID: 16489488]
[28]
Walker, M.C.; Tong, X.; Perry, H.; Alavijeh, M.S.; Patsalos, P.N. Comparison of serum, cerebrospinal fluid and brain extracellular fluid pharmacokinetics of lamotrigine. Br. J. Pharmacol., 2000, 130(2), 242-248.
[http://dx.doi.org/10.1038/sj.bjp.0703337] [PMID: 10807660]
[29]
Eisenberg, E.; Shifrin, A.; Krivoy, N. Lamotrigine for neuropathic pain. Expert Rev. Neurother., 2005, 5(6), 729-735.
[http://dx.doi.org/10.1586/14737175.5.6.729] [PMID: 16274331]
[30]
Alam, M.I.; Baboota, S.; Ahuja, A.; Ali, M.; Ali, J.; Sahni, J.K. Intranasal administration of nanostructured lipid carriers containing CNS acting drug: pharmacodynamic studies and estimation in blood and brain. J. Psychiatr. Res., 2012, 46(9), 1133-1138.
[http://dx.doi.org/10.1016/j.jpsychires.2012.05.014] [PMID: 22749490]
[31]
Vyas, T.K.; Babbar, A.K.; Sharma, R.K.; Singh, S.; Misra, A. Intranasal mucoadhesive microemulsions of clonazepam: preliminary studies on brain targeting. J. Pharm. Sci., 2006, 95(3), 570-580.
[http://dx.doi.org/10.1002/jps.20480] [PMID: 16419051]
[32]
Abbas, H.; Refai, H.; El Sayed, N. Superparamagnetic iron oxide–loaded lipid nanocarriers incorporated in thermosensitive in situ gel for magnetic brain targeting of clonazepam. J. Pharm. Sci., 2018, 107(8), 2119-2127.
[http://dx.doi.org/10.1016/j.xphs.2018.04.007] [PMID: 29665379]
[33]
Gavini, E.; Hegge, A.B.; Rassu, G.; Sanna, V.; Testa, C.; Pirisino, G.; Karlsen, J.; Giunchedi, P. Nasal administration of carbamazepine using chitosan microspheres: in vitro/in vivo studies. Int. J. Pharm., 2006, 307(1), 9-15.
[http://dx.doi.org/10.1016/j.ijpharm.2005.09.013] [PMID: 16257156]
[34]
Elshafeey, A.H.; Bendas, E.R.; Mohamed, O.H. Intranasal microemulsion of sildenafil citrate: in vitro evaluation and in vivo pharmacokinetic study in rabbits. AAPS PharmSciTech, 2009, 10(2), 361-367.
[http://dx.doi.org/10.1208/s12249-009-9213-6] [PMID: 19333762]
[35]
Hanson, L.R.; Frey, W.H., II Intranasal delivery bypasses the blood-brain barrier to target therapeutic agents to the central nervous system and treat neurodegenerative disease. BMC Neurosci., 2008, 9(3)(Suppl. 3), S5.
[http://dx.doi.org/10.1186/1471-2202-9-S3-S5] [PMID: 19091002]
[36]
Löscher, W.; Schmidt, D. New horizons in the development of antiepileptic drugs. Epilepsy Res., 2002, 50(1-2), 3-16.
[http://dx.doi.org/10.1016/S0920-1211(02)00063-3] [PMID: 12151112]
[37]
Kreuter, J. Nanoparticulate systems for brain delivery of drugs. Adv. Drug Deliv. Rev., 2001, 47(1), 65-81.
[http://dx.doi.org/10.1016/S0169-409X(00)00122-8] [PMID: 11251246]
[38]
Fielding, R.M.; Smith, P.C.; Wang, L.H.; Porter, J.; Guo, L.S. Comparative pharmacokinetics of amphotericin B after administration of a novel colloidal delivery system, ABCD, and a conventional formulation to rats. Antimicrob. Agents Chemother., 1991, 35(6), 1208-1213.
[http://dx.doi.org/10.1128/AAC.35.6.1208] [PMID: 1929263]
[39]
Chaturvedi, M.; Kumar, M.; Pathak, K. A review on mucoadhesive polymer used in nasal drug delivery system. J. Adv. Pharm. Technol. Res., 2011, 2(4), 215-222.
[http://dx.doi.org/10.4103/2231-4040.90876] [PMID: 22247888]
[40]
Gentile, P.; Chiono, V.; Carmagnola, I.; Hatton, P.V. An overview of poly(lactic-co-glycolic) acid (PLGA)-based biomaterials for bone tissue engineering. Int. J. Mol. Sci., 2014, 15(3), 3640-3659.
[http://dx.doi.org/10.3390/ijms15033640] [PMID: 24590126]
[41]
Nigam, K.; Kaur, A.; Tyagi, A.; Nematullah, M.; Khan, F.; Gabrani, R.; Dang, S. Nose-to-brain delivery of lamotrigine-loaded PLGA nanoparticles. Drug Deliv. Transl. Res., 2019, 9(5), 879-890.
[http://dx.doi.org/10.1007/s13346-019-00622-5] [PMID: 30887226]
[42]
Xie, Y.; Bagby, T.R.; Cohen, M.S.; Forrest, M.L. Drug delivery to the lymphatic system: importance in future cancer diagnosis and therapies. Expert Opin. Drug Deliv., 2009, 6(8), 785-792.
[http://dx.doi.org/10.1517/17425240903085128] [PMID: 19563270]
[43]
Jung, T.; Kamm, W.; Breitenbach, A.; Hungerer, K-D.; Hundt, E.; Kissel, T. Tetanus toxoid loaded nanoparticles from sulfobutylated poly(vinyl alcohol)-graft-poly(lactide-co-glycolide): evaluation of antibody response after oral and nasal application in mice. Pharm. Res., 2001, 18(3), 352-360.
[http://dx.doi.org/10.1023/A:1011063232257] [PMID: 11442276]
[44]
Nah, J-W.; Paek, Y-W.; Jeong, Y-I.; Kim, D-W.; Cho, C-S.; Kim, S-H.; Kim, M.Y. Clonazepam release from poly(DL-lactide-co-glycolide) nanoparticles prepared by dialysis method. Arch. Pharm. Res., 1998, 21(4), 418-422.
[http://dx.doi.org/10.1007/BF02974636] [PMID: 9875469]
[45]
Nah, J-W.; Jeong, Y-D.; Koh, J-J. Drug release from nanoparticles of Poly (DL-lactide-co-glycolide). Korean J. Chem. Eng., 2000, 17(2), 230-236.
[http://dx.doi.org/10.1007/BF02707148]
[46]
Jeong, Y.I.; Cho, C.S.; Kim, S.H.; Ko, K.S.; Kim, S.I.; Shim, Y.H. Preparation of poly (DL‐lactide‐co‐glycolide) nanoparticles without surfactant. J. Appl. Polym. Sci., 2001, 80(12), 2228-2236.
[http://dx.doi.org/10.1002/app.1326]
[47]
Pooja, D.; Tunki, L.; Kulhari, H.; Reddy, B.B.; Sistla, R. Characterization, biorecognitive activity and stability of WGA grafted lipid nanostructures for the controlled delivery of Rifampicin. Chem. Phys. Lipids, 2015, 193, 11-17.
[http://dx.doi.org/10.1016/j.chemphyslip.2015.09.008] [PMID: 26409629]
[48]
González, A.G. Optimization of pharmaceutical formulations based on response-surface experimental designs. Int. J. Pharm., 1993, 97(1-3), 149-159.
[http://dx.doi.org/10.1016/0378-5173(93)90135-3]
[49]
Spell, J.C.; Stewart, J.T. Analysis of clonazepam in a tablet dosage form using smallbore HPLC. J. Pharm. Biomed. Anal., 1998, 18(3), 453-460.
[http://dx.doi.org/10.1016/S0731-7085(98)00058-2] [PMID: 10096839]
[50]
Ranjan, A.P.; Mukerjee, A.; Helson, L.; Vishwanatha, J.K. Scale up, optimization and stability analysis of Curcumin C3 complex-loaded nanoparticles for cancer therapy. J. Nanobiotechnology, 2012, 10(1), 38.
[http://dx.doi.org/10.1186/1477-3155-10-38] [PMID: 22937885]
[51]
Romero-Pérez, A.; García-García, E.; Zavaleta-Mancera, A.; Ramírez-Bribiesca, J.E.; Revilla-Vázquez, A.; Hernández-Calva, L.M.; López-Arellano, R.; Cruz-Monterrosa, R.G. Designing and evaluation of sodium selenite nanoparticles in vitro to improve selenium absorption in ruminants. Vet. Res. Commun., 2010, 34(1), 71-79.
[http://dx.doi.org/10.1007/s11259-009-9335-z] [PMID: 20020202]
[52]
Manoochehri, S.; Darvishi, B.; Kamalinia, G.; Amini, M.; Fallah, M.; Ostad, S.N.; Atyabi, F.; Dinarvand, R. Surface modification of PLGA nanoparticles via human serum albumin conjugation for controlled delivery of docetaxel. Daru, 2013, 21(1), 58.
[http://dx.doi.org/10.1186/2008-2231-21-58] [PMID: 23866721]
[53]
Mohanraj, K.; Sethuraman, S.; Krishnan, U.M. Development of poly(butylene succinate) microspheres for delivery of levodopa in the treatment of Parkinson’s disease. J. Biomed. Mater. Res. B Appl. Biomater., 2013, 101(5), 840-847.
[http://dx.doi.org/10.1002/jbm.b.32888] [PMID: 23401377]
[54]
Elmowafy, E.; Osman, R.; El-Shamy, A.H.; Awad, G.A. Nanocomplexes of an insulinotropic drug: optimization, microparticle formation, and antidiabetic activity in rats. Int. J. Nanomedicine, 2014, 9, 4449-4465.
[PMID: 25258534]
[55]
Nasr, M. Development of an optimized hyaluronic acid-based lipidic nanoemulsion co-encapsulating two polyphenols for nose to brain delivery. Drug Deliv., 2016, 23(4), 1444-1452.
[http://dx.doi.org/10.3109/10717544.2015.1092619] [PMID: 26401600]
[56]
Sood, S.; Jain, K.; Gowthamarajan, K. Optimization of curcumin nanoemulsion for intranasal delivery using design of experiment and its toxicity assessment. Colloids Surf. B Biointerfaces, 2014, 113, 330-337.
[http://dx.doi.org/10.1016/j.colsurfb.2013.09.030] [PMID: 24121076]
[57]
Kaur, A.; Saxena, Y.; Bansal, R.; Gupta, S.; Tyagi, A.; Sharma, R.K.; Ali, J.; Panda, A.K.; Gabrani, R.; Dang, S. Intravaginal delivery of polyphenon 60 and curcumin nanoemulsion gel. AAPS PharmSciTech, 2017, 18(6), 2188-2202.
[http://dx.doi.org/10.1208/s12249-016-0652-6] [PMID: 28070848]
[58]
Babbar, A; Kashyap, R; Chauhan, U. A convenient method for the preparation of 99mTc-labelled pentavalent DMSA and its evaluation as a tumour imaging agent Journal of nuclear biology and medicine (Turin, Italy: 1991), 1991, 35(2), 100-104.
[59]
Sharma, D.; Sharma, R.K.; Sharma, N.; Gabrani, R.; Sharma, S.K.; Ali, J.; Dang, S. Nose-to-brain delivery of PLGA-diazepam nanoparticles. AAPS PharmSciTech, 2015, 16(5), 1108-1121.
[http://dx.doi.org/10.1208/s12249-015-0294-0] [PMID: 25698083]
[60]
Boschi, A.; Uccelli, L.; Martini, P. A Picture of Modern Tc-99m Radiopharmaceuticals: Production, Chemistry, and Applications in Molecular Imaging. Appl. Sci. (Basel), 2019, 9(12), 2526.
[http://dx.doi.org/10.3390/app9122526]
[61]
Psimadas, D.; Bouziotis, P.; Georgoulias, P.; Valotassiou, V.; Tsotakos, T.; Loudos, G. Radiolabeling approaches of nanoparticles with (99m). Tc. Contrast Media Mol. Imaging, 2013, 8(4), 333-339.
[http://dx.doi.org/10.1002/cmmi.1530] [PMID: 23613436]
[62]
Kaul, A.; Chaturvedi, S.; Attri, A.; Kalra, M.; Mishra, A. Targeted theranostic liposomes: rifampicin and ofloxacin loaded pegylated liposomes for theranostic application in mycobacterial infections. RSC Advances, 2016, 6(34), 28919-28926.
[http://dx.doi.org/10.1039/C6RA01135G]
[63]
Keck, P.E., Jr; McElroy, S.L. Clinical pharmacodynamics and pharmacokinetics of antimanic and mood-stabilizing medications. J. Clin. Psychiatry 2002, 63(Suppl. 4), 3-11.
[PMID: 11913673]
[64]
Kumar, M.; Misra, A.; Babbar, A.K.; Mishra, A.K.; Mishra, P.; Pathak, K. Intranasal nanoemulsion based brain targeting drug delivery system of risperidone. Int. J. Pharm., 2008, 358(1-2), 285-291.
[http://dx.doi.org/10.1016/j.ijpharm.2008.03.029] [PMID: 18455333]
[65]
Lalani, J.; Rathi, M.; Lalan, M.; Misra, A. Protein functionalized tramadol-loaded PLGA nanoparticles: preparation, optimization, stability and pharmacodynamic studies. Drug Dev. Ind. Pharm., 2013, 39(6), 854-864.
[http://dx.doi.org/10.3109/03639045.2012.684390] [PMID: 22799442]
[66]
Jain, S.; Mittal, A.K.; Jain, A. R Mahajan R, Singh D. Cyclosporin A loaded PLGA nanoparticle: preparation, optimization, in-vitro characterization and stability studies. Curr. Nanosci., 2010, 6(4), 422-431.
[http://dx.doi.org/10.2174/157341310791658937]
[67]
Kalaria, D.R.; Sharma, G.; Beniwal, V.; Ravi Kumar, M.N. Design of biodegradable nanoparticles for oral delivery of doxorubicin: in vivo pharmacokinetics and toxicity studies in rats. Pharm. Res., 2009, 26(3), 492-501.
[http://dx.doi.org/10.1007/s11095-008-9763-4] [PMID: 18998202]
[68]
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), 181-194.
[http://dx.doi.org/10.1517/17425247.2014.945416] [PMID: 25164097]
[69]
Subedi, R.K.; Kang, K.W.; Choi, H-K. Preparation and characterization of solid lipid nanoparticles loaded with doxorubicin. Eur. J. Pharm. Sci., 2009, 37(3-4), 508-513.
[http://dx.doi.org/10.1016/j.ejps.2009.04.008] [PMID: 19406231]
[70]
Shah, K.A.; Date, A.A.; Joshi, M.D.; Patravale, V.B. Solid lipid nanoparticles (SLN) of tretinoin: potential in topical delivery. Int. J. Pharm., 2007, 345(1-2), 163-171.
[http://dx.doi.org/10.1016/j.ijpharm.2007.05.061] [PMID: 17644288]
[71]
Lalani, J.; Patil, S.; Kolate, A.; Lalani, R.; Misra, A. Protein-functionalized PLGA nanoparticles of lamotrigine for neuropathic pain management. AAPS PharmSciTech, 2015, 16(2), 413-427.
[http://dx.doi.org/10.1208/s12249-014-0235-3] [PMID: 25354788]
[72]
Sawant, K.K.; Dodiya, S.S. Recent advances and patents on solid lipid nanoparticles. Recent Pat. Drug Deliv. Formul., 2008, 2(2), 120-135.
[http://dx.doi.org/10.2174/187221108784534081] [PMID: 19075903]
[73]
Kedar, U.; Phutane, P.; Shidhaye, S.; Kadam, V. Advances in polymeric micelles for drug delivery and tumor targeting. Nanomedicine (Lond.), 2010, 6(6), 714-729.
[http://dx.doi.org/10.1016/j.nano.2010.05.005] [PMID: 20542144]
[74]
Jia, L.; Shen, J.; Li, Z.; Zhang, D.; Zhang, Q.; Liu, G.; Zheng, D.; Tian, X. In vitro and in vivo evaluation of paclitaxel-loaded mesoporous silica nanoparticles with three pore sizes. Int. J. Pharm., 2013, 445(1-2), 12-19.
[http://dx.doi.org/10.1016/j.ijpharm.2013.01.058] [PMID: 23384728]
[75]
Jia, L-J.; Zhang, D-R.; Li, Z-Y.; Feng, F-F.; Wang, Y-C.; Dai, W-T.; Duan, C.X.; Zhang, Q. Preparation and characterization of silybin-loaded nanostructured lipid carriers. Drug Deliv., 2010, 17(1), 11-18.
[http://dx.doi.org/10.3109/10717540903431586] [PMID: 19941406]
[76]
Cojocaru, V.; Ranetti, A.E.; Hinescu, L.G.; Ionescu, M.; Cosmescu, C.; Poștoarcă, A.G. Formulation and evaluation of in vitro release kinetics of Na3CaDTPA decorporation agent embedded in microemulsion-based gel formulation for topical delivery. Farmacia, 2015, 63(5), 656-664.
[77]
Singhvi, G.; Singh, M. In-vitro drug release characterization models. Int J Pharm Stud Res., 2011, 2(1), 77-84.
[78]
Kim, D-H.; Martin, D.C. Sustained release of dexamethasone from hydrophilic matrices using PLGA nanoparticles for neural drug delivery. Biomaterials, 2006, 27(15), 3031-3037.
[http://dx.doi.org/10.1016/j.biomaterials.2005.12.021] [PMID: 16443270]
[79]
Feng, S-S. Nanoparticles of biodegradable polymers for new-concept chemotherapy. Expert Rev. Med. Devices, 2004, 1(1), 115-125.
[http://dx.doi.org/10.1586/17434440.1.1.115] [PMID: 16293015]
[80]
Kushwaha, S.K.; Keshari, R.K.; Rai, A. Advances in nasal trans-mucosal drug delivery. J. Appl. Pharm. Sci., 2011, 1(7), 21.
[81]
Nigam, K.; Kaur, A.; Tyagi, A.; Manda, K.; Gabrani, R.; Dang, S. Baclofen-loaded poly (d, l-lactide-co-glycolic acid) nanoparticles for neuropathic pain management: in vitro and in vivo evaluation. Rejuvenation Res., 2019, 22(3), 235-245.
[http://dx.doi.org/10.1089/rej.2018.2119] [PMID: 30175946]
[82]
Musumeci, T.; Bonaccorso, A.; Puglisi, G. Epilepsy Disease and Nose-to-Brain Delivery of Polymeric Nanoparticles: An Overview. Pharmaceutics, 2019, 11(3), 118.
[http://dx.doi.org/10.3390/pharmaceutics11030118] [PMID: 30871237]
[83]
Nour, S.A.; Abdelmalak, N.S.; Naguib, M.J.; Rashed, H.M.; Ibrahim, A.B. Intranasal brain-targeted clonazepam polymeric micelles for immediate control of status epilepticus: in vitro optimization, ex vivo determination of cytotoxicity, in vivo biodistribution and pharmacodynamics studies. Drug Deliv., 2016, 23(9), 3681-3695.
[http://dx.doi.org/10.1080/10717544.2016.1223216] [PMID: 27648847]
[84]
Wieber, A.; Selzer, T.; Kreuter, J. Characterisation and stability studies of a hydrophilic decapeptide in different adjuvant drug delivery systems: a comparative study of PLGA nanoparticles versus chitosan-dextran sulphate microparticles versus DOTAP-liposomes. Int. J. Pharm., 2011, 421(1), 151-159.
[http://dx.doi.org/10.1016/j.ijpharm.2011.09.011] [PMID: 21945740]
[85]
Yadav, K.S.; Sawant, K.K. Modified nanoprecipitation method for preparation of cytarabine-loaded PLGA nanoparticles. AAPS PharmSciTech, 2010, 11(3), 1456-1465.
[http://dx.doi.org/10.1208/s12249-010-9519-4] [PMID: 20842542]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy