Skip to main content

Advertisement

SpringerLink
Log in

RETRACTED ARTICLE: Poloxamer-407-Co-Poly (2-Acrylamido-2-Methylpropane Sulfonic Acid) Cross-linked Nanogels for Solubility Enhancement of Olanzapine: Synthesis, Characterization, and Toxicity Evaluation

  • Research Article
  • Published:
AAPS PharmSciTech Aims and scope Submit manuscript

This article was retracted on 21 February 2024

This article has been updated

Abstract

Current study is focused to enhance the solubility of poorly soluble drug olanzapine (OLZ) by nanogels drug delivery system, as improved solubility is one of the most important applications of nanosystems. Poor solubility is a major issue, and 40% of marketed and about 75% of new active pharmaceutical ingredients are poorly water soluble which significantly affect the bioavailability and therapeutic effects of these drugs. In this study, nanogels, a promising system for solubility enhancement, were developed by free-radical polymerization technique. Different formulations were synthesized in which poloxamer-407 was cross-linked with 2-acrylamido-2-methylpropane sulfonic acid (AMPS) with the help of cross-linker methylene bisacrylamide (MBA). The chemically cross-linked nanogels were characterized by Fourier transform infrared spectroscopy (FT-IR), thermos gravimetric analysis (TGA), differential scanning calorimetry (DSC), X-ray diffraction (XRD), scanning electron microscopy (SEM), zeta size, swelling, sol-gel analysis, drug loading, solubility, and in vitro drug release studies. In order to determine the biocompatibility and cytotoxicity of nanogels to biological system, toxicity study on rabbits was also carried out. It was confirmed that the developed nanogels was thermally stable, safe, effective, and compatible to biological system, and the solubility of olanzapine (OLZ) was enhanced up to 38 folds as compared with reference product.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11
Fig. 12

Similar content being viewed by others

Change history

References

  1. Jermain SV, Brough C, Williams RO III. Amorphous solid dispersions and nanocrystal technologies for poorly water-soluble drug delivery–an update. Int J Pharm. 2018;535(1–2):379–92.

    Article  CAS  PubMed  Google Scholar 

  2. Xie Y, Yao Y. Octenylsuccinate hydroxypropyl phytoglycogen, a dendrimer-like biopolymer, solubilizes poorly water-soluble active pharmaceutical ingredients. Carbohydr Polym. 2018;180:29–37.

    Article  CAS  PubMed  Google Scholar 

  3. Abdelkader H, Fathalla Z. Investigation into the emerging role of the basic amino acid L-lysine in enhancing solubility and permeability of BCS class II and BCS class IV drugs. Pharm Res. 2018;35(8):160.

    Article  PubMed  Google Scholar 

  4. Tambe A, Pandita N. Enhanced solubility and drug release profile of boswellic acid using a poloxamer-based solid dispersion technique. Journal of Drug Delivery Science and Technology. 2018;44:172–80.

    Article  CAS  Google Scholar 

  5. Yousaf AM, et al. Fabrication and in vitro characterization of fenofibric acid-loaded hyaluronic acid–polyethylene glycol polymeric composites with enhanced drug solubility and dissolution rate. Int J Polym Mater Polym Biomater. 2018:1–6.

  6. Malamatari M, Taylor KMG, Malamataris S, Douroumis D, Kachrimanis K. Pharmaceutical nanocrystals: production by wet milling and applications. Drug Discov Today. 2018;23(3):534–47.

    Article  CAS  PubMed  Google Scholar 

  7. Li H, Li H, Wei C, Ke J, Li J, Xu L, et al. Biomimetic synthesis and evaluation of histidine-derivative templated chiral mesoporous silica for improved oral delivery of the poorly water-soluble drug, nimodipine. Eur J Pharm Sci. 2018;117:321–30.

    Article  CAS  PubMed  Google Scholar 

  8. de França Almeida CDL, et al. Amorphous solid dispersions of hecogenin acetate using different polymers for enhancement of solubility and improvement of anti-hyperalgesic effect in neuropathic pain model in mice. Biomed Pharmacother. 2018;97:870–9.

    Article  Google Scholar 

  9. Eleraky NE, Swarnakar NK, Mohamed DF, Attia MA, Pauletti GM. Permeation-enhancing nanoparticle formulation to enable oral absorption of enoxaparin. AAPS PharmSciTech. 2020;21(3):88.

    Article  CAS  PubMed  Google Scholar 

  10. Cheng M, et al. Fabrication of fine puerarin nanocrystals by Box–Behnken design to enhance intestinal absorption. AAPS PharmSciTech. 2020;21(3):1–12.

    Article  Google Scholar 

  11. Sita V, Vavia P. Bromocriptine nanoemulsion-loaded transdermal gel: optimization using factorial design, in vitro and in vivo evaluation. AAPS PharmSciTech. 2020;21(3):80.

    Article  CAS  Google Scholar 

  12. Wang W, Li M, Yang Q, Liu Q, Ye M, Yang G. The opposed effects of polyvinylpyrrolidone K30 on dissolution and precipitation for indomethacin supersaturating drug delivery systems. AAPS PharmSciTech. 2020;21(3):107.

    Article  PubMed  Google Scholar 

  13. Naqvi A, Ahmad M, Minhas MU, Khan KU, Batool F, Rizwan A. Preparation and evaluation of pharmaceutical co-crystals for solubility enhancement of atorvastatin calcium. Polym Bull. 2019.

  14. Kabanov AV, Vinogradov SV. Nanogels as pharmaceutical carriers: finite networks of infinite capabilities. Angew Chem Int Ed. 2009;48(30):5418–29.

    Article  CAS  Google Scholar 

  15. Zhang Y, Andrén OCJ, Nordström R, Fan Y, Malmsten M, Mongkhontreerat S, et al. Off-stoichiometric thiol-ene chemistry to dendritic nanogel therapeutics. Adv Funct Mater. 2019;29:1806693.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Kendre PN, Satav TS. Current trends and concepts in the design and development of nanogel carrier systems. Polym Bull. 2019;76(3):1595–617.

    Article  CAS  Google Scholar 

  17. Grimaudo MA, Amato G, Carbone C, Diaz-Rodriguez P, Musumeci T, Concheiro A, et al. Micelle-nanogel platform for ferulic acid ocular delivery. Int J Pharm. 2020;576:118986.

    Article  CAS  PubMed  Google Scholar 

  18. Suhail M, Rosenholm JM, Minhas MU, Badshah SF, Naeem A, Khan KU, et al. Nanogels as drug-delivery systems: a comprehensive overview. Ther Deliv. 2019;10(11):697–717.

    Article  CAS  PubMed  Google Scholar 

  19. Soni G, Yadav KS. Nanogels as potential nanomedicine carrier for treatment of cancer: a mini review of the state of the art. Saudi Pharmaceutical Journal. 2016;24(2):133–9.

    Article  PubMed  Google Scholar 

  20. Dorwal D. Nanogels as novel and versatile pharmaceuticals. Int J Pharm Pharm Sci. 2012;4(3):67–74.

    CAS  Google Scholar 

  21. Sultana F, et al. An overview of nanogel drug delivery system. J Appl Pharm Sci. 2013;3(8):95–105.

    Google Scholar 

  22. Sasaki Y, Akiyoshi K. Nanogel engineering by associating polymers for biomedical applications. Hydrogel Micro and Nanoparticles. 2012:187–208.

  23. Zhang L, Hu Y, Jiang X, Yang C, Lu W, Yang YH. Camptothecin derivative-loaded poly(caprolactone-co-lactide)-b-PEG-b-poly(caprolactone-co-lactide) nanoparticles and their biodistribution in mice. J Control Release. 2004;96(1):135–48.

    Article  CAS  PubMed  Google Scholar 

  24. Fakhari A, Corcoran M, Schwarz A. Thermogelling properties of purified poloxamer 407. Heliyon. 2017;3(8):e00390.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Dumortier G, Grossiord JL, Agnely F, Chaumeil JC. A review of poloxamer 407 pharmaceutical and pharmacological characteristics. Pharm Res. 2006;23(12):2709–28.

    Article  CAS  PubMed  Google Scholar 

  26. Kolašinac N, Kachrimanis K, Homšek I, Grujić B, Đurić Z, Ibrić S. Solubility enhancement of desloratadine by solid dispersion in poloxamers. Int J Pharm. 2012;436(1–2):161–70.

    Article  PubMed  Google Scholar 

  27. Szafraniec J, Antosik A, Knapik-Kowalczuk J, Chmiel K, Kurek M, Gawlak K, et al. Enhanced dissolution of solid dispersions containing bicalutamide subjected to mechanical stress. Int J Pharm. 2018;542(1–2):18–26.

    Article  CAS  PubMed  Google Scholar 

  28. Ren L, et al. Chronic treatment with the modified Longdan Xiegan Tang attenuates olanzapine-induced fatty liver in rats by regulating hepatic de novo lipogenesis and fatty acid beta-oxidation-associated gene expression mediated by SREBP-1c. PPAR-alpha and AMPK-alpha. 2019;232:176–87.

    Google Scholar 

  29. Uno Y, Coyle JT. Glutamate hypothesis in schizophrenia. Psychiatry Clin Neurosci. 2019;73:204–15.

    Article  PubMed  Google Scholar 

  30. López-González I, Pinacho R, Vila È, Escanilla A, Ferrer I, Ramos B. Neuroinflammation in the dorsolateral prefrontal cortex in elderly chronic schizophrenia. Eur Neuropsychopharmacol. 2019;29:384–96.

    Article  PubMed  Google Scholar 

  31. Schafer, M., et al., Imaging habenula volume in schizophrenia and bipolar disorder. 2018. 9.

  32. McGinty J, Haque MS, Upthegrove RJSr. Depression during first episode psychosis and subsequent suicide risk: a systematic review and meta-analysis of longitudinal studies. Schizophr Res. 2018;195:58–66.

    Article  PubMed  Google Scholar 

  33. Bhuyan, D., et al., Mood, motor, and speech abnormalities in schizophrenia, mania, and other psychotic disorders: a comparative analysis 2019. 10(1): p. 68–72.

  34. Buckly P., et al., Psychiatric comorbidities and schizofrenia 2009. 35(2): p. 383–402.

  35. Ng-Mak, D., et al., Hospitalization risk in bipolar disorder patients treated with lurasidone versus other atypical antipsychotics 2019. 35(2): p. 211–219.

  36. Si TM, et al. Switching to paliperidone extended release in patients with schizophrenia dissatisfied with previous olanzapine treatment: post hoc analysis of an open-label, prospective study. Medicine. 2019;98(3).

  37. de Freitas MR, et al. Inclusion complex of methyl-β-cyclodextrin and olanzapine as potential drug delivery system for schizophrenia. Carbohydr Polym. 2012;89(4):1095–100.

    Article  CAS  PubMed  Google Scholar 

  38. Zhuang T, Zhang W, Cao L, He K, Wang Y, Li J, et al. Isolation, identification and characterization of two novel process-related impurities in olanzapine. J Pharm Biomed Anal. 2018;152:188–96.

    Article  CAS  PubMed  Google Scholar 

  39. Rudrangi SRS, Trivedi V, Mitchell JC, Wicks SR, Alexander BD. Preparation of olanzapine and methyl-β-cyclodextrin complexes using a single-step, organic solvent-free supercritical fluid process: an approach to enhance the solubility and dissolution properties. Int J Pharm. 2015;494(1):408–16.

    Article  CAS  PubMed  Google Scholar 

  40. de Mohac LM, de Fátima Pina M, Raimi-Abraham BT. Solid microcrystalline dispersion films as a new strategy to improve the dissolution rate of poorly water soluble drugs: a case study using olanzapine. Int J Pharm. 2016;508(1–2):42–50.

    Article  Google Scholar 

  41. Pontes-Neto JG, Fontes DAF, de Lyra MAM, Brito MRM, Chaves LL, Rolim-Neto PJ, et al. Evaluation of antioxidant potencial of novel CaAl and NiAl layered double hydroxides loaded with olanzapine. Life Sci. 2018;207:246–52.

    Article  CAS  PubMed  Google Scholar 

  42. Gadhave DG, Tagalpallewar AA, Kokare CR. Agranulocytosis-protective olanzapine-loaded nanostructured lipid carriers engineered for CNS delivery: optimization and hematological toxicity studies. AAPS PharmSciTech. 2019;20(1):22.

    Article  PubMed  Google Scholar 

  43. Shabuddin, M., et al. Formulation and evaluation of fast dissolving oral films of olanzapine. 2018.

  44. Testa CG, Prado LD, Costa RN, Costa ML, Linck YG, Monti GA, et al. Challenging identification of polymorphic mixture: polymorphs I, II and III in olanzapine raw materials. Int J Pharm. 2019;556:125–35.

    Article  CAS  PubMed  Google Scholar 

  45. Anup N, Thakkar S, Misra M. Formulation of olanzapine nanosuspension based orally disintegrating tablets (ODT); comparative evaluation of lyophilization and electrospraying process as solidification techniques. Adv Powder Technol. 2018;29(8):1913–24.

    Article  CAS  Google Scholar 

  46. Jeon S-Y, et al. A randomized, double-blind, placebo-controlled study of the safety and efficacy of olanzapine for the prevention of chemotherapy-induced nausea and vomiting in patients receiving moderately emetogenic chemotherapy: results of the Korean South West Oncology Group (KSWOG) study. Cancer Research and Treatment. 2019;51(1):90.

    Article  CAS  PubMed  Google Scholar 

  47. Dixit M, et al. Enhancing solubility and dissolution of olanzapine by spray drying using β-cyclodextrin polymer. J Appl Pharm Sci. 2014;4(11):81–6.

    Google Scholar 

  48. Abdullah O, Usman Minhas M, Ahmad M, Ahmad S, Ahmad A. Synthesis of hydrogels for combinatorial delivery of 5-fluorouracil and leucovorin calcium in colon cancer: optimization, in vitro characterization and its toxicological evaluation. Polym Bull. 2019;76(6):3017–37.

    Article  CAS  Google Scholar 

  49. Khalid Q, Ahmad M, Usman Minhas M. Hydroxypropyl-β-cyclodextrin hybrid nanogels as nano-drug delivery carriers to enhance the solubility of dexibuprofen: characterization, in vitro release, and acute oral toxicity studies. Adv Polym Technol. 2018;37(6):2171–85.

    Article  CAS  Google Scholar 

  50. Rao, K.M., et al., Novel thermo/pH sensitive nanogels composed from poly (N-vinylcaprolactam) for controlled release of an anticancer drug. 2013;102:891–897.

  51. Drozd KV, Manin AN, Churakov AV, Perlovich GL. Drug-drug cocrystals of antituberculous 4-aminosalicylic acid: screening, crystal structures, thermochemical and solubility studies. Eur J Pharm Sci. 2017;99:228–39.

    Article  CAS  PubMed  Google Scholar 

  52. Sayed E, Karavasili C, Ruparelia K, Haj-Ahmad R, Charalambopoulou G, Steriotis T, et al. Electrosprayed mesoporous particles for improved aqueous solubility of a poorly water soluble anticancer agent: in vitro and ex vivo evaluation. J Control Release. 2018;278:142–55.

    Article  CAS  PubMed  Google Scholar 

  53. Bhaskar K, Anbu J, Ravichandiran V, Venkateswarlu V, Rao Y. Lipid nanoparticles for transdermal delivery of flurbiprofen: formulation, in vitro, ex vivo and in vivo studies. Lipids Health Dis. 2009;8(1):6.

    Article  PubMed  PubMed Central  Google Scholar 

  54. Guo C, et al. Optimization of extended-release ZL-004 nanosuspensions for in vivo pharmacokinetic study to enhance low solubility and compliance. Molecules. 2019;24(1):7.

    Article  Google Scholar 

  55. Ren X, Qi J, Wu W, Yin Z, Li T, Lu Y. Development of carrier-free nanocrystals of poorly water-soluble drugs by exploring metastable zone of nucleation. Acta Pharm Sin B. 2019;9(1):118–27.

    Article  PubMed  Google Scholar 

  56. Madgulkar A, Bhalekar M, Khabiya PN. Nanoparticulates of fenofibrate for solubility enhancement: ex-vivo evaluation. Journal of Drug Delivery and Therapeutics. 2019;9(4):155–63.

    Google Scholar 

  57. Rodríguez-Rodríguez R, Velasquillo-Martínez C, Knauth P, López Z, Moreno-Valtierra M, Bravo-Madrigal J, et al. Sterilized chitosan-based composite hydrogels: physicochemical characterization and in vitro cytotoxicity. J Biomed Mater Res A. 2020;108(1):81–93.

    Article  PubMed  Google Scholar 

  58. Nasir N, Ahmad M, Minhas MU, Barkat K, Khalid MF. pH-responsive smart gels of block copolymer [pluronic F127-co-poly (acrylic acid)] for controlled delivery of ivabradine hydrochloride: its toxicological evaluation. J Polym Res. 2019;26(9):212.

    Article  CAS  Google Scholar 

  59. Yin L, Fei L, Cui F, Tang C, Yin C. Superporous hydrogels containing poly (acrylic acid-co-acrylamide)/O-carboxymethyl chitosan interpenetrating polymer networks. Biomaterials. 2007;28(6):1258–66.

    Article  CAS  PubMed  Google Scholar 

  60. Ullah K, Ali Khan S, Murtaza G, Sohail M, Azizullah, Manan A, et al. Gelatin-based hydrogels as potential biomaterials for colonic delivery of oxaliplatin. Int J Pharm. 2019;556:236–45.

    Article  CAS  PubMed  Google Scholar 

  61. Bode C, Kranz H, Fivez A, Siepmann F, Siepmann J. Often neglected: PLGA/PLA swelling orchestrates drug release: HME implants. J Control Release. 2019;306:97–107.

    Article  CAS  PubMed  Google Scholar 

  62. Jain S, Ancheria RK, Shrivastava S, Soni SL, Sharma M. An overview of nanogel–novel drug delivery system. Asian Journal of Pharmaceutical Research and Development. 2019;7(2):47–55.

    Article  Google Scholar 

  63. Taleb MA, Hegazy DE, Mahmoud GA. Characterization and in vitro drug release behavior of (2-hydroxyethyl methacrylate)–co-(2-acrylamido-2-methyl-1-propanesulfonic acid) crosslinked hydrogels prepared by ionizing radiation. Int J Polym Mater Polym Biomater. 2014;63(16):840–5.

    Article  CAS  Google Scholar 

  64. Hazer O, Soykan C, Kartal Ş. Synthesis and swelling behavior analysis of poly (acrylamidoxime-co-2-acrylamido-2-methylpropane sulfonic acid) hydrogels. Journal of Macromolecular Science, Part A: Pure and Applied Chemistry. 2007;45(1):45–51.

    Article  Google Scholar 

  65. Zhang Y, Wu FP, Li MZ, Wang EJ. pH switching on-off semi-IPN hydrogel based on cross-linked poly (acrylamide-co-acrylic acid) and linear polyallyamine. Polymer. 2005;46(18):7695–700.

    Article  CAS  Google Scholar 

  66. Minhas MU, et al. Functionalized pectin hydrogels by cross-linking with monomer: synthesis, characterization, drug release and pectinase degradation studies. Polym Bull. 2019:1–18.

  67. Üzüm ÖB, et al. Swelling behaviors of novel magnetic semi-IPN hydrogels and their application for Janus Green B removal. Polym Bull. 2019:1–21.

  68. Broglia, M.F., et al., Acid hydrogel matrixes as reducing/stabilizing agent for the in-situ synthesis of Ag-nanocomposites by UV irradiation: pH effect. Materials Research Express, 2019.

  69. Pontes-Neto JG, Lyra MAM, Soares MFLR, Chaves LL, Soares-Sobrinho JL. Intercalation of olanzapine into CaAl and NiAl layered double hydroxides for dissolution rate improvement: synthesis, characterization and in vitro toxicity. Journal of Drug Delivery Science and Technology. 2019;52:986–96.

    Article  CAS  Google Scholar 

Download references

Funding

This research was supported by the Higher Education Commission (HEC) of Pakistan.

Author information

Authors and Affiliations

  1. Faculty of Pharmacy and Alternative Medicine, The Islamia University of Bahawalpur, Bahawalpur, Punjab, 63100, Pakistan

    Kifayat Ullah Khan & Naveed Akhtar

  2. College of Pharmacy, University of Sargodha, University Road, Sargodha City, Punjab, Pakistan

    Muhammad Usman Minhas

Authors
  1. Kifayat Ullah Khan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Naveed Akhtar
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Muhammad Usman Minhas
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Muhammad Usman Minhas.

Ethics declarations

Declaration of Interests

The authors declare that they have no conflict of interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article has been retracted. Please see the retraction notice for more detail: https://doi.org/10.1208/s12249-024-02768-z

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Khan, K.U., Akhtar, N. & Minhas, M.U. RETRACTED ARTICLE: Poloxamer-407-Co-Poly (2-Acrylamido-2-Methylpropane Sulfonic Acid) Cross-linked Nanogels for Solubility Enhancement of Olanzapine: Synthesis, Characterization, and Toxicity Evaluation. AAPS PharmSciTech 21, 141 (2020). https://doi.org/10.1208/s12249-020-01694-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1208/s12249-020-01694-0

KEY WORDS

Search

Navigation