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Improving lithium carbonate therapeutics by pegylated liposomal technology: an in vivo study

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Abstract

Bipolar disorder is a chronic mental illness which is associated with high risk of self-harm and suicide. Lithium carbonate has been suggested as a medicine to control and cure this disease. To overcome the complications related to taking lithium carbonate, nanotechnology has come to the aid of scientists. In this study, pegylated liposomal lithium carbonate nanoparticles were prepared by the reverse phase evaporation method to improve the drug’s therapeutic characteristics as well as lessening its side effects. In order to synthesize pegylated liposomal lithium carbonate, phosphatidylcholine, polyethylene glycol 3350 (PEG3350), cholesterol, and lithium carbonate were mixed. The characterization of synthesized nanoparticles was determined by Zetasizer. Encapsulation and drug loading efficiency and release pattern studies were determined through spectrophotometry method. In addition, serum lithium and creatinine levels of the samples were analyzed. The mean diameter, size distribution, and zeta potential for pegylated liposomal particles containing lithium carbonate and blank pegylated liposomal were determined by Zetasizer equal to 102 nm, 0.458, and −25.1 mV; 284.2 nm, 0.427, and −28.3 mV, respectively. Drug loading and encapsulation efficiency were calculated to be 32.87 and 97.4 %, respectively. The drug release pattern demonstrated that the half-life of the nanodrug was approximately two times higher than the standard drug. The results related to the analysis of serum lithium and creatinine levels indicated that the efficiency of liposomal drug formulation was increased compared to the standard drug. Based on the findings, the nanodrug enjoyed a half-life two times higher than that of the standard drug and an efficiency level equal to it.

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References

  • Amarnath S, Sharma US (1997) Liposomes in drug delivery: progress and limitations. Int J Pharm 154:123–140

    Article  Google Scholar 

  • Ani M, Moshtaghie AA, Akbarzadeh S (2005) Changes in biochemical parameters related to lipid metabolism following lithium treatment in rat. Iran Biomed J 9:27–32

    CAS  Google Scholar 

  • Cervantes F, Mesa R, Barosi G (2007) New and old treatment modalities in primary myelofibrosis. Cancer J 13:377–383

    Article  CAS  PubMed  Google Scholar 

  • Chen CH, Suckling J, Lennox BR, Ooi C, Bullmore ET (2011) A quantitative meta-analysis of fMRI studies in bipolar disorder. Bipolar Disord 13:1–15

    Article  CAS  PubMed  Google Scholar 

  • Cheng HC, Chang CY, Hsieh FI, Yeh JJ, Chien MY, Pan RN, Deng MC, Liu DZ (2011) Effects of tremella-alginate-liposome encapsulation on oral delivery of inactivated H5N3 vaccine. J Microencapsul 28:55–61

    Article  CAS  PubMed  Google Scholar 

  • Cheong I, Zhou S (2009) Tumor-specific liposomal drug release mediated by liposomase. Methods Enzymol 465:251–265

    Article  CAS  PubMed  Google Scholar 

  • Christian GD (2002) Reagents for lithium electrodes and sensors for blood serum analysis. Sensors 2:432–435

    Article  CAS  Google Scholar 

  • Chudal R, Sucksdorff D, Suominen A, Lehti V, Hinkka-Yli-Salomäki S, Huttunen J, Ristkari T, Gissler M, McKeague IW, Brown AS, Sourander A (2014) Finnish prenatal study of bipolar disorders (FIPS-B): overview, design and description of the sample. Nord J Psychiatry 68:169–179

    Article  PubMed  Google Scholar 

  • Clough Z, Henry R, Ekelund A (2014) Delirium associated with therapeutic levels of lithium in bipolar disorder. Prog Neurol Psychiatry 18:10–12

    Article  Google Scholar 

  • Costantino L, Boraschi D (2012) Is there a clinical future for polymeric nanoparticles as brain-targeting drug delivery agents? Drug Discov Today 17:367–378

    Article  CAS  PubMed  Google Scholar 

  • Dikpati A, Madgulkar AR, Kshirsagar SJ, Bhalekar MR, Singh Chahal A (2012) Targeted drug delivery to CNS using nanoparticles. J Adv Pharm Sci 2:79–191

    Google Scholar 

  • Espirito Santo CE, Carvalho TMJP (2014) Determination of serum lithium: comparison between atomic emission and absorption spectrometry methods. J Bras Patol Med Lab 49:12

    Article  Google Scholar 

  • Fountoulakis KN, Kelsoe JR, Akiskal H (2012) Receptor targets for antidepressant therapy in bipolar disorder: an overview. J Affect Disord 138:222–238

    Article  CAS  PubMed  Google Scholar 

  • Fukumoto T, Morinobu S, Okamoto Y, Kagaya A, Yamawaki S (2001) Chronic lithium treatment increases the expression of brain-derived neurotrophic factor in the rat brain. Psychopharmacology (Berlin) 158:100–106

    Article  CAS  Google Scholar 

  • Geddes JR, Miklowitz DJ (2013) Treatment of bipolar disorder. Lancet 381:1672–1682

    Article  CAS  PubMed  Google Scholar 

  • Goodwin GM, Consensus Group of the British Association for Psychopharmacology (2009) Evidence-based guidelines for treating bipolar disorder: revised second edition--recommendations from the British Association for Psychopharmacology. J Psychopharmacol 23:346–388

    Article  CAS  PubMed  Google Scholar 

  • Handa T, Naito S, Hiramatsu M, Tsuboi M (2006) Thermal SiO and H13CO+ line observations of the dense molecular cloud G0.11-0.11 in the galactic center region. Astrophys J 636:261–266

    Article  CAS  Google Scholar 

  • Himanshu A, Sitasharan P, Singhai AK (2011) Liposomes as drug carriers. IJPLS 2:945–951

    Google Scholar 

  • Irache JM, Esparza I, Gamazo C, Agüeros M, Espuelas S (2011) Nanomedicine: novel approaches in human and veterinary therapeutics. Vet Parasitol 180:47–71

    Article  PubMed  Google Scholar 

  • Italia JL, Bhatt DK, Bhardwaj V, Tikoo K, Kumar MN (2007) PLGA nanoparticles for oral delivery of cyclosporine: nephrotoxicity and pharmacokinetic studies in comparison to Sandimmune Neoral. J Control Release 119:197–206

    Article  CAS  PubMed  Google Scholar 

  • Iwanaga K, Ono S, Narioka K, Kakemi M, Morimoto K, Yamashita S, Namba Y, Oku N (1999) Application of surface-coated liposomes for oral delivery of peptide: effects of coating the liposome’ssurface on the GI transit of insulin. J Pharm Sci 88:248–252

    Article  CAS  PubMed  Google Scholar 

  • Jurgons R, Seliger C, Hilpert A, Trahms L, Odenbach S, Alexiou C (2006) Drug loaded magnetic nanoparticles for cancer therapy. J Phys Condens Matter 18:S2893–S2902

    Article  CAS  Google Scholar 

  • Kawai F (2002) Microbial degradation of polyethers. Appl Microbiol Biotechnol 58:30–38

    Article  CAS  PubMed  Google Scholar 

  • Lasic DD (1998) Novel applications of liposomes. Trends Biotechnol 16:307–321

    Article  CAS  PubMed  Google Scholar 

  • Leyhe T, Eschweiler GW, Stransky E, Gasser T, Annas P, Basun H, Laske C (2009) Increase of BDNF serum concentration in lithium treated patients with early Alzheimer’s disease. J Alzheimers Dis 16:649–656

    CAS  PubMed  Google Scholar 

  • Lian T, Ho RJ (2001) Trends and developments in liposome drug delivery systems. J Pharm Sci 90:667–680

    Article  CAS  PubMed  Google Scholar 

  • Madetoja J, Madetoja M, Mäkinen J, Riuttala E, Jokinen J (2009) Blood sampling from the tail vein, in comparison with two other techniques, causes less stress to mice. Scand J Lab Anim Sci 36:215–221

    CAS  Google Scholar 

  • Masserini M (2013) Nanoparticles for brain drug delivery. ISRN Biochem 2013:18

    Article  Google Scholar 

  • Michelon L, Vallada H (2005) Fatores genéticos e ambientais na manifestação do transtorno bipolar. Rev Psiq Clin 32:21–27

    Article  Google Scholar 

  • Mu L, Feng SS (2003) PLGA/TPGS nanoparticles for controlled release of paclitaxel: effects of the emulsifier and drug loading ratio. Pharm Res 20:1864–1872

    Article  CAS  PubMed  Google Scholar 

  • Nakase I, Lai H, Singh NP, Sasaki T (2008) Anticancer properties of artemisinin derivatives and their targeted delivery by transferrin conjugation. Int J Pharm 354:28–33

    Article  CAS  PubMed  Google Scholar 

  • Ning Z, Cheung CS, Fu J, Liu MA, Schnell MA (2006) Experimental study of environmental tobacco smoke particles under actual indoor environment. Sci Total Environ 367:822–830

    Article  CAS  PubMed  Google Scholar 

  • Ochekpe NA, Olorunfemi PO, Ngwuluka NC (2009) Nanotechnology and drug delivery. Part 1: background and applications. Trop J Pharm Res 8:265–274

    CAS  Google Scholar 

  • Olya S, Khorvash M, Rahmani HR, Esmaeilkhanian S, Olya B, Sadri H (2014) Oral delivery of insulin-loaded nanoparticles in diabetic rabbits and in sheep. Czech J Anim Sci 59:251–256

    Google Scholar 

  • Otsuka H, Nagasaki Y, Kataoka K (2012) PEGylated nanoparticles for biological and pharmaceutical applications. Adv Drug Deliv Rev 64:246–255

    Article  Google Scholar 

  • Sadock BJ, Sadock VA, Ruiz P (2009) Kaplan and Sadock’s comprehensive textbook of psychiatry (2 volume set). Lippincott Williams & Wilkins (LWW), Philadelphia

    Google Scholar 

  • Shallie PD, Adefule AK, Akpan HB, Fakoya D, Adejumo EN (2010) Analysis of some lipid parameters following lithium administration. Afr J Pharm Pharacol 4:202–206

    CAS  Google Scholar 

  • Smith AJ, Kim SH, Duggirala NK, Jin J, Wojtas L, Ehrhart J, Giunta B, Tan J, Zaworotko MJ, Shytle RD (2013) Improving lithium therapeutics by crystal engineering of novel ionic cocrystals. Mol Pharm 10:4728–4738

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • William ZP, Leo EH (2006) Antipsychotic agents & lithium. In: Bertram G (ed) Basic and clinical pharmacology America: K LANGE medical book. McGraw-Hill Companies, Columbus, pp 490–495

    Google Scholar 

  • Yang T, Choi MK, Cui FD, Kim JS, Chung SJ, Shim CK, Kim DD (2007) Preparation and evaluation of paclitaxel-loaded PEGylated immunoliposome. J Control Release 120:169–177

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Seyed Ebrahim Alavi or Azim Akbarzadeh.

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Hosseini, Y., Alavi, S.E., Akbarzadeh, A. et al. Improving lithium carbonate therapeutics by pegylated liposomal technology: an in vivo study. Comp Clin Pathol 25, 211–218 (2016). https://doi.org/10.1007/s00580-015-2172-2

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  • DOI: https://doi.org/10.1007/s00580-015-2172-2

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