Skip to main content
Disciplines
Automotive Business IT + Informatics Construction + Real Estate Electrical Engineering + Electronics Energy + Sustainability Insurance + Risk Finance + Banking Management + Leadership Marketing + Sales Mechanical Engineering + Materials
Events
DE
EN
Books
Journals
Topic Page
Marketing
Start single access now
Access for companies
EXTENDED SEARCH
Log in
Top
Colloid and Polymer Science

06-04-2024 | Research

Spray dried mebendazole–loaded Soluplus-based polymeric micelles for improved biopharmaceutical attributes: in vitro and in vivo studies

Authors: Tania Bajaj, Ghanshyam Das Gupta, Charan Singh

Published in: Colloid and Polymer Science

Log in

Activate our intelligent search to find suitable subject content or patents.

search-config
loading …

Abstract

The aim of this research was to investigate spray-dried mebendazole (MBZ)–loaded Soluplus-based polymeric micelles (MBZ@PMs) for improved solubility and bioabsorption upon oral administration. Following the MBZ@PM preparation, the formed micellar preparation was examined using FTIR, PXRD, DSC, and TEM techniques to determine its physical and chemical properties. Critical micelle concentration determination studies showed that Soluplus® can effectively generate stable polymeric micelles. Particle size analysis demonstrated spherical shape and a particle size of 538.7 ± 2.129 nm. Solubility studies demonstrated approximately eight times higher solubility of MBZ@PMs vis-à-vis MBZ in PBS pH 6.8 (90.16 ± 2.54 µg/mL v/s 11.97 ± 2.99 µg/mL). Stability studies confirmed that the size distribution and polydispersity index of the prepared polymeric micelles showed negligible variations. In vitro release studies revealed low MBZ release from MBZ@PMs (9.70 ± 3.2% in 2 h) at pH 1.2 and sustained (33.3 ± 3.9%) at PBS pH 6.8 in 48 h. In vivo pharmacokinetic studies showed approximately fourfold higher bioavailability (AUC0-ꝏ 153.81 ± 24.20 v/s 38.20 ± 5.55) and 1.5-fold extended half-life of MBZ from MBZ@PMs (2.13 ± 0.53 v/s 1.44 ± 0.36). Therefore, these unprecedented Soluplus®-based polymeric micelles of Mebendazole can be applied as a potential carrier system to improve the therapeutic efficacy of poorly water-soluble compounds.

Graphical Abstract

Dont have a licence yet? Then find out more about our products and how to get one now:

Springer Professional "Wirtschaft+Technik"

Online-Abonnement

Mit Springer Professional "Wirtschaft+Technik" erhalten Sie Zugriff auf:

  • über 102.000 Bücher
  • über 537 Zeitschriften

aus folgenden Fachgebieten:

  • Automobil + Motoren
  • Bauwesen + Immobilien
  • Business IT + Informatik
  • Elektrotechnik + Elektronik
  • Energie + Nachhaltigkeit
  • Finance + Banking
  • Management + Führung
  • Marketing + Vertrieb
  • Maschinenbau + Werkstoffe
  • Versicherung + Risiko

Jetzt Wissensvorsprung sichern!

inform now

Springer Professional "Technik"

Online-Abonnement

Mit Springer Professional "Technik" erhalten Sie Zugriff auf:

  • über 67.000 Bücher
  • über 390 Zeitschriften

aus folgenden Fachgebieten:

  • Automobil + Motoren
  • Bauwesen + Immobilien
  • Business IT + Informatik
  • Elektrotechnik + Elektronik
  • Energie + Nachhaltigkeit
  • Maschinenbau + Werkstoffe




 

Jetzt Wissensvorsprung sichern!

inform now
Literature
1.
Lavelle EC, Sharif S, Thomas NW, Holland J, Davis SS (1995) The importance of gastrointestinal uptake of particles in the design of oral delivery systems. Adv Drug Deliv Rev 18(1):5–22CrossRef
2.
Deshpande AA, Rhodes CT, Shah NH, Malick AW (1996) Controlled-release drug delivery systems for prolonged gastric residence: an overview. Drug Dev Ind Pharm 22(6):531–539CrossRef
3.
Dian L, Yang Z, Li F, Wang Z, Pan X, Peng X, Huang X, Guo Z, Quan G, Shi X, Chen B (2013) Cubic phase nanoparticles for sustained release of ibuprofen: formulation, characterization, and enhanced bioavailability study. Int J Nanomed 8:845
4.
Johnston AP, Such GK, Ng SL, Caruso F (2011) Challenges facing colloidal delivery systems: from synthesis to the clinic. Curr Opin Colloid Interface Sci 16(3):171–181CrossRef
5.
Grotz E, Tateosian NL, Salgueiro J, Bernabeu E, Gonzalez L, Manca ML, Amiano N, Valenti D, Manconi M, García V, Moretton MA (2019) Pulmonary delivery of rifampicin-loaded soluplus micelles against Mycobacterium tuberculosis. Journal of Drug Delivery Science and Technology 1(53):101170CrossRef
6.
Al-Akayleh F, Zakari Z, Adwan S, Al-Remawi M (2020) Preparation, characterization and ex-vivo human skin permeation of ibuprofen-soluplus polymeric nanomicelles. Int J Pharm Sci Res 12:2863–2869
7.
8.
Chen JM, Wang ZZ, Wu CB, Li S, Lu TB (2012) Crystal engineering approach to improve the solubility of mebendazole. CrystEngComm 14(19):6221–6229CrossRef
9.
Canete R, Escobedo AA, Almirall P, Gonzalez ME, Brito K, Cimerman S (2009) Mebendazole in parasitic infections other than those caused by soil-transmitted helminths. Trans R Soc Trop Med Hyg 103(5):437–442PubMedCrossRef
10.
Garg A, Singh C, Pradhan D, Ghosh G, Rath G (2020) Topical application of nanoparticles integrated supramolecular hydrogels for the potential treatment of seborrhoeic dermatitis. Pharm Dev Technol 25(6):748–756PubMedCrossRef
11.
Singh C, Koduri LS, Dhawale V, Bhatt TD, Kumar R, Grover V, Tikoo K, Suresh S (2015) Potential of aerosolized rifampicin lipospheres for modulation of pulmonary pharmacokinetics and bio-distribution. Int J Pharm 495(2):627–632PubMedCrossRef
12.
Devasari N, Dora CP, Singh C, Paidi SR, Kumar V, Sobhia ME, Suresh S (2015) Inclusion complex of erlotinib with sulfobutyl ether-β-cyclodextrin: preparation, characterization, in silico, in vitro and in vivo evaluation. Carbohyd Polym 10(134):547–556CrossRef
13.
Singh C, Bhatt TD, Gill MS, Suresh S (2014) Novel rifampicin–phospholipid complex for tubercular therapy: synthesis, physicochemical characterization and in-vivo evaluation. Int J Pharm 460(1–2):220–227PubMedCrossRef
14.
Dora CP, Trotta F, Kushwah V, Devasari N, Singh C, Suresh S, Jain S (2016) Potential of erlotinibcyclodextrinnanosponge complex to enhance solubility, dissolution rate, in vitro cytotoxicity and oral bioavailability. Carbohyd Polym 10(137):339–349CrossRef
15.
Ghasemiyeh P, Mohammadi-Samani S (2018) Solid lipid nanoparticles and nanostructured lipid carriers as novel drug delivery systems: applications, advantages and disadvantages. Research in pharmaceutical sciences 13(4):288PubMedPubMedCentralCrossRef
16.
Bajaj T, Singh C, Gupta GD (2022) Novel metal organic frameworks improves solubility and oral absorption of mebendazole: physicochemical characterization and in vitro-in vivo evaluation. Journal of Drug Delivery Science and Technology 1(70):103264CrossRef
17.
Bhuptani RS, Jain AS, Makhija DT, Jagtap AG, Hassan PA, Nagarsenker MS (2016) Soluplus based polymeric micelles and mixed micelles of lornoxicam: design, characterization and In vivo efficacy studies in rats. Indian Journal of Pharmaceutical Education and Research 50(2):277–286
18.
Qi X, Gao C, Yin C, Fan J, Wu X, Guo C (2021) Improved anticancer activity of betulinic acid on breast cancer through a grafted copolymer-based micelles system. Drug Delivery 28(1):1962–1971PubMedPubMedCentralCrossRef
19.
Sipos B, Csóka I, Ambrus R, Schelz Z, Zupkó I, Balogh GT, Katona G (2022) Spray-dried indomethacin-loaded polymeric micelles for the improvement of intestinal drug release and permeability. Eur J Pharm Sci 1(174):106200CrossRef
20.
Rezazadeh M, Davatsaz Z, Emami J, Hasanzadeh F, Jahanian-Najafabadi A (2018) Preparation and characterization of spray-dried inhalable powders containing polymeric micelles for pulmonary delivery of paclitaxel in lung cancer. J Pharm Pharm Sci 21(1s):200s-s214PubMedCrossRef
21.
Ding Y, Wang C, Wang Y, Xu Y, Zhao J, Gao M, Ding Y, Peng J, Li L (2018) Development and evaluation of a novel drug delivery: Soluplus®/TPGS mixed micelles loaded with piperine in vitro and in vivo. Drug Dev Ind Pharm 44(9):1409–1416PubMedCrossRef
22.
Zeng YC, Li S, Liu C, Gong T, Sun X, Fu Y, Zhang ZR (2017) Soluplus micelles for improving the oral bioavailability of scopoletin and their hypouricemic effect in vivo. Acta PharmacologicaSinica 38(3):424–433CrossRef
23.
Chaudhary S, Garg T, Rath G, Murthy RR, Goyal AK (2016) Enhancing the bioavailability of mebendazole by integrating the principles solid dispersion and nanocrystal techniques, for safe and effective management of human echinococcosis. Artificial Cells, Nanomedicine, and Biotechnology 44(3):937–942PubMed
24.
Wang S, Ye F, Wei F, Zhao G (2017) Spray-drying of curcumin-loaded octenylsuccinated corn dextrin micelles stabilized with maltodextrin. Powder Technol 1(307):56–62CrossRef
25.
Aboul‐Enein HY, Bunaciu AA, Fleschin S (2002) Analysis of mebendazole polymorphs by Fourier transform IR spectrometry using chemometric methods. Biopolymers: Original Research on Biomolecules 67(1):56–60CrossRef
26.
Jena SK, Singh C, Dora CP, Suresh S (2014) Development of tamoxifen-phospholipid complex: novel approach for improving solubility and bioavailability. Int J Pharm 473(1–2):1–9PubMedCrossRef
27.
Zhang Z, Cui C, Wei F, Lv H (2017) Improved solubility and oral bioavailability of apigenin via Soluplus/Pluronic F127 binary mixed micelles system. Drug Dev Ind Pharm 43(8):1276–1282PubMedCrossRef
28.
Ji S, Lin X, Yu E, Dian C, Yan X, Li L, Zhang M, Zhao W, Dian L (2018) Curcumin-loaded mixed micelles: preparation, characterization, and in vitro antitumor activity. Journal of Nanotechnology 1:2018
29.
Zhou Y, Wang C, Liu W, Yang M, Xu B, Chen Y (2022) Fast in vitro release and in vivo absorption of an anti-schizophrenic drug paliperidone from its Soluplus®/TPGS mixed micelles. Pharmaceutics 14(5):889PubMedPubMedCentralCrossRef
30.
Li G, Lu Y, Fan Y, Ning Q, Li W (2020) Enhanced oral bioavailability of magnolol via mixed micelles and nanosuspensions based on Soluplus®-Poloxamer 188. Drug Delivery 27(1):1010–1017PubMedPubMedCentralCrossRef
31.
Jin IS, Jo MJ, Park CW, Chung YB, Kim JS, Shin DH (2020) Physicochemical, pharmacokinetic, and toxicity evaluation of soluplus® polymeric micelles encapsulating fenbendazole. Pharmaceutics 12(10):1000PubMedPubMedCentralCrossRef
32.
33.
Bhattacharjee S (2016) DLS and zeta potential—what they are and what they are not? J Control Release 10(235):337–351CrossRef
34.
Elzoghby AO, Helmy MW, Samy WM, Elgindy NA (2013) Spray-dried casein-based micelles as a vehicle for solubilization and controlled delivery of flutamide: formulation, characterization, and in vivo pharmacokinetics. Eur J Pharm Biopharm 84(3):487–496PubMedCrossRef
35.
Zhao J, Xu Y, Wang C, Ding Y, Chen M, Wang Y, Peng J, Li L, Lv L (2017) Soluplus/TPGS mixed micelles for dioscin delivery in cancer therapy. Drug Dev Ind Pharm 43(7):1197–1204PubMedCrossRef
36.
Agatonovic-Kustrin S, Glass BD, Mangan M, Smithson J (2008) Analysing the crystal purity of mebendazole raw material and its stability in a suspension formulation. Int J Pharm 361(1–2):245–250PubMedCrossRef
37.
Kumar S, Chawla G, Sobhia ME, Bansal AK (2008) Characterization of solid-state forms of mebendazole. Die Pharmazie-An International Journal of Pharmaceutical Sciences 63(2):136–143
38.
Shamma RN, Basha M (2013) Soluplus®: a novel polymeric solubilizer for optimization of carvedilol solid dispersions: formulation design and effect of method of preparation. Powder Technol 1(237):406–414CrossRef
39.
Bonde GV, Ajmal G, Yadav SK, Mittal P, Singh J, Bakde BV, Mishra B (2020) Assessing the viability of Soluplus® self-assembled nanocolloids for sustained delivery of highly hydrophobic lapatinib (anticancer agent): Optimisation and in-vitro characterisation. Colloids Surf, B 1(185):110611CrossRef
40.
Brusau EV, Camí GE, Narda GE, Cuffini S, Ayala AP, Ellena J (2008) Synthesis and characterization of a new mebendazole salt: mebendazole hydrochloride. J Pharm Sci 97(1):542–552PubMedCrossRef
41.
Liebenberg W, Dekker TG, Lotter AP, De Villiers MM (1998) Identification of the mebendazole polymorphic form present in raw materials and tablets available in South Africa. Drug Dev Ind Pharm 24(5):485–488PubMedCrossRef
42.
De Villiers MM, Terblanche RJ, Liebenberg W, Swanepoel E, Dekker TG, Song M (2005) Variable-temperature X-ray powder diffraction analysis of the crystal transformation of the pharmaceutically preferred polymorph C of mebendazole. J Pharm Biomed Anal 38(3):435–441PubMedCrossRef
43.
Altamimi MA, Neau SH (2017) Investigation of the in vitro performance difference of drug-Soluplus® and drug-PEG 6000 dispersions when prepared using spray drying or lyophilization. Saudi Pharmaceutical Journal 25(3):419–439PubMedCrossRef
44.
Piazzini V, D’Ambrosio M, Luceri C, Cinci L, Landucci E, Bilia AR, Bergonzi MC (2019) Formulation of nanomicelles to improve the solubility and the oral absorption of silymarin. Molecules 24(9):1688PubMedPubMedCentralCrossRef
45.
Alopaeus JF, Hagesæther E, Tho I (2019) Micellisation mechanism and behaviour of Soluplus®–furosemide micelles: preformulation studies of an oral nanocarrier-based system. Pharmaceuticals 12(1):15PubMedPubMedCentralCrossRef
46.
Dian L, Yu E, Chen X, Wen X, Zhang Z, Qin L, Wang Q, Li G, Wu C (2014) Enhancing oral bioavailability of quercetin using novel soluplus polymeric micelles. Nanoscale Res Lett 9(1):1–1CrossRef
47.
Singh J, Mittal P, VasantBonde G, Ajmal G, Mishra B (2018) Design, optimization, characterization and in-vivo evaluation of Quercetin enveloped Soluplus®/P407 micelles in diabetes treatment. Artificial Cells, Nanomedicine, and Biotechnology 46(sup3):S546–S555PubMedCrossRef
48.
Rani S, Mishra S, Sharma M, Nandy A, Mozumdar S (2020) Solubility and stability enhancement of curcumin in Soluplus® polymeric micelles: a spectroscopic study. J Dispersion Sci Technol 41(4):523–536CrossRef
49.
50.
Lim C, Ramsey JD, Hwang D, Teixeira SC, Poon CD, Strauss JD, Rosen EP, Sokolsky-Papkov M, Kabanov AV (2022) Drug-dependent morphological transitions in spherical and worm-like polymeric micelles define stability and pharmacological performance of micellar drugs. Small 18(4):2103552CrossRef
51.
Pignatello R, Corsaro R, Bonaccorso A, Zingale E, Carbone C, Musumeci T (2022) Soluplus® polymeric nanomicelles improve solubility of BCS-class II drugs. Drug Deliv Transl Res 12(8):1991–2006PubMedPubMedCentralCrossRef
52.
Naksuriya O, Shi Y, Van Nostrum CF, Anuchapreeda S, Hennink WE, Okonogi S (2015) HPMA-based polymeric micelles for curcumin solubilization and inhibition of cancer cell growth. Eur J Pharm Biopharm 1(94):501–512CrossRef
Metadata
Title
Spray dried mebendazole–loaded Soluplus-based polymeric micelles for improved biopharmaceutical attributes: in vitro and in vivo studies
Authors
Tania Bajaj
Ghanshyam Das Gupta
Charan Singh
Publication date
06-04-2024
Publisher
Springer Berlin Heidelberg
Published in
Colloid and Polymer Science
Print ISSN: 0303-402X
Electronic ISSN: 1435-1536
DOI
https://doi.org/10.1007/s00396-024-05251-0

Premium Partners

    Image Credits