Skip to main content

Advertisement

SpringerLink
Log in

Development and Characterization of PCL Electrospun Membrane-Coated Bletilla striata Polysaccharide-Based Gastroretentive Drug Delivery System

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

Abstract

The purpose of this study was to investigate the potential of Bletilla striata polysaccharide (BSP, a natural glucomannan material) for the development of a gastroretentive drug delivery system for the first time. Novel BSP-based porous wafer was prepared for levofloxacin hydrochloride (LFH) delivery by combining floating, swelling, and mucoadhesion mechanisms. The influences of BSP and ethyl cellulose (EC) on drug release and mucoadhesive strength were studied by 32 factorial design. The optimized matrix was coated with polycaprolactone (PCL) electrospun membrane by electrospinning and heat treatment technology. The optimized formula (F6, coated) exhibited Q4 h of 41.20 ± 1.90%, Q8 h of 76.49 ± 1.69%, and mucoadhesive strength of 86.11 ± 1.33 gf, and its drug release profile most closely resembled the Korsmeyer–Peppas model with anomalous diffusion driving mechanism. F6 (coated) also presented excellent buoyancy, preferred swelling characteristic due to the porous structure formed by freeze-drying. Meanwhile, the internal morphology, physical state, drug–excipient compatibility, and thermal behavior were recorded. The negligible cytotoxicity of F6 (coated) was observed in human gastric epithelial cell cultures. In the in vitro antimicrobial experiment, the prepared wafer exhibited obvious bacterial inhibition zone, and due to its longer gastric retention, the wafer also performed a more effective Helicobacter pylori clearance than free LFH in vivo.

Graphical abstract

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

Similar content being viewed by others

Abbreviations

BSP:

Bletilla striata polysaccharide

DSC:

Differential scanning calorimeter

EC:

Ethyl cellulose

FTIR:

Fourier transform infrared spectroscopy

GES-1:

Human gastric mucosal epithelial cells

GRDDS:

Gastroretentive drug delivery system

H. pylori :

Helicobacter pylori

LFH:

Levofloxacin hydrochloride

PCL:

Polycaprolactone

Q 4 h :

Cumulative release of the drug at 4 h

Q 8 h :

Cumulative release of the drug at 8 h

References

  1. El-Zahaby SA, Kassem AA, El-Kamel AH. Design and evaluation of gastroretentive levofloxacin floating mini-tablets-in-capsule system for eradication of Helicobacter pylori. Saudi Pharmaceutical Journal. 2014;22(6):570–9.

    Article  Google Scholar 

  2. Antos D, Schneider-Brachert W, Bästlein E, Hänel C, Haferland C, Buchner M, et al. 7-Day triple therapy of Helicobacter pylori infection with levofloxacin, amoxicillin, and high-dose esomeprazole in patients with known antimicrobial sensitivity. Helicobacter. 2006;11(1):39–45.

    Article  CAS  Google Scholar 

  3. Bera H, Maiti S, Saha S, Nayak AK. Biopolymers-based gastroretentive buoyant systems for therapeutic management of Helicobacter pylori infection. Polysaccharide Carriers for Drug Delivery; 2019. 713–736 p.

  4. Lopes CM, Bettencourt C, Rossi A, Buttini F, Barata P. Overview on gastroretentive drug delivery systems for improving drug bioavailability. Int J Pharm. 2016;510(1):144–58.

    Article  CAS  Google Scholar 

  5. Hwang KM, Cho CH, Tung NT, Kim JY, Rhee YS, Park ES. Release kinetics of highly porous floating tablets containing cilostazol. Eur J Pharm Biopharm. 2017;115(2):39–51.

    Article  CAS  Google Scholar 

  6. Tadros MI. Controlled-release effervescent floating matrix tablets of ciprofloxacin hydrochloride: development, optimization and in vitro-in vivo evaluation in healthy human volunteers. Eur J Pharm Biopharm. 2010;74(2):332–9.

    Article  CAS  Google Scholar 

  7. Rajput P, Singh D, Pathak K. Bifunctional capsular dosage form: novel fanicular cylindrical gastroretentive system of clarithromycin and immediate release granules of ranitidine HCl for simultaneous delivery. Int J Pharm. 2014;461(1–2):310–21.

    Article  CAS  Google Scholar 

  8. Patel A, Modasiya M, Shah D, Patel V. Development and in vivo floating behavior of verapamil HCl intragastric floating tablets. AAPS PharmSciTech. 2009;10(1):310–5.

    Article  CAS  Google Scholar 

  9. Bhalla S, Nagpal M. Comparison of various generations of superporous hydrogels based on chitosan-acrylamide and in vitro drug release. ISRN Pharmaceutics. 2013;2013:1–8.

    Article  Google Scholar 

  10. Su C-Y, Ho H-O, Chen Y-C, Yu Y-T, Liu D-Z, Chao F-C, et al. Complex hydrogels composed of chitosan with ring-opened polyvinyl pyrrolidone as a gastroretentive drug dosage form to enhance the bioavailability of bisphosphonates. Sci Rep. 2018;8(1):1–12.

    Google Scholar 

  11. Ruiz-Caro R, Veiga MD. In vitro evaluation of acyclovir/chitosan floating systems. Materials. 2010;3(12):5195–211.

    Article  CAS  Google Scholar 

  12. Kim JY, Kim SH, Rhee YS, Park CW, Park ES. Preparation of hydroxypropylmethyl cellulose-based porous matrix for gastroretentive delivery of gabapentin using the freeze-drying method. Cellulose. 2013;20(6):3143–54.

    Article  CAS  Google Scholar 

  13. Mandal UK, Chatterjee B, Senjoti FG. Gastro-retentive drug delivery systems and their in vivo success: a recent update. Int J Pharm. 2016.

  14. Auriemma G, Cerciello A, Sansone F, Morello S, Aquino RP. Polysaccharides based gastroretentive system to sustain piroxicam release: development and in vivo prolonged anti-inflammatory effect. Int J Biol Macromol. 2018.

  15. Yao J. Tiao He Yi Wei granule, a traditional Chinese medicine, against ethanol-induced gastric ulcer in mice. Evid Based Complement Alternat Med. 2015;2015:1–8.

    CAS  Google Scholar 

  16. Qu Y, Li C, Zhang C, Zeng R, Fu C. Optimization of infrared-assisted extraction of Bletilla striata polysaccharides based on response surface methodology and their antioxidant activities. Carbohydr Polym. 2016;148:345–53.

    Article  CAS  Google Scholar 

  17. Liao Z, Zeng R, Hu L, Maffucci KG, Qu Y. Polysaccharides from tubers of Bletilla striata: physicochemical characterization, formulation of buccoadhesive wafers and preliminary study on treating oral ulcer. Int J Biol Macromol. 2019;122:1035–45.

    Article  CAS  Google Scholar 

  18. Hu L, Liao Z, Hu Q, Maffucci KG, Qu Y. Novel Bletilla striata polysaccharide microneedles: fabrication, characterization, and in vitro transcutaneous drug delivery. Int J Biol Macromol. 2018;117:928–36.

    Article  CAS  Google Scholar 

  19. Cui X, Zhang X, Yang Y, Wang C, Zhang C, Peng G. Preparation and evaluation of novel hydrogel based on polysaccharide isolated from Bletilla striata. Pharm Dev Technol. 2017;22(8):1001–11.

    Article  CAS  Google Scholar 

  20. Kim JY, Seo JW, Rhee YS, Park CW, Park ES. Freeze-dried highly porous matrix as a new gastroretentive dosage form for ecabet sodium: in vitro and in vivo characterizations. J Pharm Sci. 2014;103(1):262–73.

    Article  CAS  Google Scholar 

  21. Said Z, Baker SR, Hansen J, D’Apice K, Thornhill MH, Madsen LS, et al. Pre-clinical evaluation of novel mucoadhesive bilayer patches for local delivery of clobetasol-17-propionate to the oral mucosa. Biomaterials. 2018;178:134–46.

    Article  Google Scholar 

  22. Lee WL, Tan JWM, Tan CN, Loo SCJ. Modulating drug release from gastric-floating microcapsules through spray-coating layers. PLoS One. 2014;9(12):1–16.

    Google Scholar 

  23. Abriata JP, Turatti RC, Luiz MT, Raspantini GL, Tofani LB, do Amaral RLF, et al. Development, characterization and biological in vitro assays of paclitaxel-loaded PCL polymeric nanoparticles. Materials Science and Engineering C. 2019;96:347–55.

  24. Qi X, Chen H, Rui Y, Yang F, Ma N, Wu Z. Floating tablets for controlled release of ofloxacin via compression coating of hydroxypropyl cellulose combined with effervescent agent. Int J Pharm. 2015;489(1–2):210–7.

    Article  CAS  Google Scholar 

  25. Zhao Q, Gao B, Ma L, Lian J, Deng L, Chen J. Innovative intragastric ascaridole floating tablets: development, optimization, and in vitro-in vivo evaluation. Int J Pharm. 2015;496(2):432–9.

    Article  CAS  Google Scholar 

  26. College JSS, Nagar SS. Development of a gastroretentive drug delivery system based on superporous hydrogel. N Vishal Gupta * and HG Shivakumar. 2010;9(6):257–64.

  27. Sharma OP, Shah MV, Parikh DC, Mehta TA. Formulation optimization of gastroretentive drug delivery system for allopurinol using experimental design. Expert Opinion on Drug Delivery. 2014;12(4):513–24.

    Article  Google Scholar 

  28. El-Zahaby SA, Kassem AA, El-Kamel AH. Formulation and in vitro evaluation of size expanding gastro-retentive systems of levofloxacin hemihydrate. Int J Pharm. 2014;464(1–2):10–8.

    Article  CAS  Google Scholar 

  29. Canal C, Aparicio RM, Esquena J, Girona J, Group TE. Drug delivery properties of macroporous polystyrene solid foams. J Pharm Pharm Sci. 2012;15(1):197–207.

    Article  CAS  Google Scholar 

  30. Hao S, Wang Y, Wang B. Sinking-magnetic microparticles prepared by the electrospray method for enhanced gastric antimicrobial delivery. Mol Pharm. 2014;11(5):1640–50.

    Article  CAS  Google Scholar 

  31. Hao S, Wang Y, Wang B, Zou Q, Zeng H, Chen X, et al. A novel gastroretentive porous microparticle for anti-Helicobacter pylori therapy: preparation, in vitro and in vivo evaluation. Int J Pharm. 2014;463(1):10–21.

    Article  CAS  Google Scholar 

  32. Siafaka PI, Zisi AP, Exindari MK, Karantas ID, Bikiaris DN. Porous dressings of modified chitosan with poly(2-hydroxyethyl acrylate) for topical wound delivery of levofloxacin. Carbohydr Polym. 2016;143:90–9.

    Article  CAS  Google Scholar 

  33. Aoki H, Iwao Y, Mizoguchi M, Noguchi S, Itai S. Clarithromycin highly-loaded gastro-floating fine granules prepared by high-shear melt granulation can enhance the efficacy of Helicobacter pylori eradication. Eur J Pharm Biopharm. 2015;2:2–7.

    Google Scholar 

  34. Zhang X, Zhang Y, Han H. Formulation optimization of gastro-retention tablets of paeonol and efficacy in treatment of experimental gastric ulcer. Chem Pharm Bull. 2017;1200.

  35. Gambhire MN, Ambade KW, Kurmi SD, Kadam VJ, Jadhav KR. Development and in vitro evaluation of an oral floating matrix tablet formulation of diltiazem hydrochloride. AAPS PharmSciTech. 2007;8(3):E166–74.

    Article  Google Scholar 

  36. Priyadarshini R, Nandi G, Changder A, Chowdhury S, Chakraborty S, Ghosh LK. Gastroretentive extended release of metformin from methacrylamide-g-gellan and tamarind seed gum composite matrix. Carbohydrate Polymers. 2015.

  37. Ahmed A, Getti G, Boateng J. Ciprofloxacin-loaded calcium alginate wafers prepared by freeze-drying technique for potential healing of chronic diabetic foot ulcers. Drug Delivery and Translational Research. 2018;8(6):1751–68.

    Article  CAS  Google Scholar 

  38. Acharya S, Patra S, Pani NR. Optimization of HPMC and carbopol concentrations in non-effervescent floating tablet through factorial design. Carbohydrate Polymers. 2014;102(1).

  39. Hauptstein S, Müller C, Dünnhaupt S, Laffleur F, Bernkop-schnürch A. Preactivated thiomers: evaluation of gastroretentive minitablets. Int J Pharm. 2013:1–7.

  40. Qin C, Wu M, Xu S, Wang X, Shi W, Dong Y, et al. Design and optimization of gastro-floating sustained-release tablet of pregabalin: in vitro and in vivo evaluation. International Journal of Pharmaceutics. 2018;545(1–2).

  41. Bera H, Gaini C, Kumar S, Sarkar S, Boddupalli S, Ippagunta SR. HPMC-based gastroretentive dual working matrices coated with Ca+ 2ion crosslinked alginate-fenugreek gum gel membrane. Mater Sci Eng C. 2016;67:170–81.

    Article  CAS  Google Scholar 

  42. Bera H, Ippagunta SR, Kumar S, Vangala P. Core-shell alginate-ghatti gum modified montmorillonite composite matrices for stomach-specific flurbiprofen delivery. Mater Sci Eng C. 2017;76:715–26.

    Article  CAS  Google Scholar 

  43. Jalvandi J, White M, Gao Y, Truong YB, Padhye R, Kyratzis IL. Polyvinyl alcohol composite nanofibres containing conjugated levofloxacin-chitosan for controlled drug release. Mater Sci Eng C. 2017;73:440–6.

    Article  CAS  Google Scholar 

  44. Islan GA, Cacicedo ML, Bosio VE, Castro GR. Development and characterization of new enzymatic modified hybrid calcium carbonate microparticles to obtain nano-architectured surfaces for enhanced drug loading. J Colloid Interface Sci. 2015;439:76–87.

    Article  CAS  Google Scholar 

  45. Imam SS, Nasir S, Bukhari A, Ahmed J, Ali A. Formulation and optimization of levofloxacin loaded chitosan nanoparticle for ocular delivery: in-vitro characterization, ocular tolerance and antibacterial activity. International Journal of Biological Macromolecules. 2017.

  46. Chen Z, Cheng L, He Y, Wei X. Extraction, characterization, utilization as wound dressing and drug delivery of Bletilla striata polysaccharide: a review. Int J Biol Macromol. 2018.

  47. Zhang C, Gao F, Gan S, He Y, Chen Z, Liu X, et al. Chemical characterization and gastroprotective effect of an isolated polysaccharide fraction from Bletilla striata against ethanol-induced acute gastric ulcer. Food Chem Toxicol. 2019;131(5):110539.

    Article  CAS  Google Scholar 

  48. Islan GA, Dini C, Bartel LC, Bolzán AD, Castro GR. Characterization of smart auto-degradative hydrogel matrix containing alginate lyase to enhance levofloxacin delivery against bacterial biofilms. Int J Pharm. 2015;496(2):953–64.

    Article  CAS  Google Scholar 

  49. Verma A, Dubey J, Hegde RR, Rastogi V, Pandit JK. Helicobacter pylori: past, current and future treatment strategies with gastroretentive drug delivery systems. J Drug Target. 2016;24(10):897–915.

    Article  CAS  Google Scholar 

  50. Huanbutta K, Sangnim T. Design and development of zero-order drug release gastroretentive floating tablets fabricated by 3D printing technology. Journal of Drug Delivery Science and Technology. 2019;52(5):831–7.

    Article  CAS  Google Scholar 

Download references

Funding

This research was supported by the National Natural Science Foundation of China (81603309), the National Key Research and Development Program of China (2017YFC1700705), the Sichuan Provincial Scholars for Science and Technology Activities for Overseas Researchers (2018-68), and the Key Projects of Central Universities (2018NZD18).

Author information

Authors and Affiliations

  1. Pharmacy College, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, People’s Republic of China

    Zhouying Li, Ling Yang & Yan Qu

  2. College of Pharmacy, Southwest University for Nationalities, Chengdu, 610041, People’s Republic of China

    Rui Zeng

  3. Department of Pharmacy, Guizhou Provincial People’s Hospital, Guiyang, 550002, People’s Republic of China

    Xiaodong Ren

  4. Department of Chemistry, Stony Brook University, Stony Brook, New York, 11794, USA

    Katherine G. Maffucci

Authors
  1. Zhouying Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rui Zeng
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ling Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xiaodong Ren
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Katherine G. Maffucci
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yan Qu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yan Qu.

Ethics declarations

Ethical Approval

All the animal experiments were approved and supervised/conducted by the Chengdu University of Traditional Chinese Medicine Ethics Committee of Care and Use of Laboratory Animals, and the animals were house and handled according to the University Unit for Laboratory Animal Medicine guidelines.

Conflict of Interest

The authors declare that they have no conflicts of interest.

Additional information

Publisher’s Note

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

Electronic Supplementary Material

ESM 1

(DOCX 74 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Li, Z., Zeng, R., Yang, L. et al. Development and Characterization of PCL Electrospun Membrane-Coated Bletilla striata Polysaccharide-Based Gastroretentive Drug Delivery System. AAPS PharmSciTech 21, 66 (2020). https://doi.org/10.1208/s12249-019-1607-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1208/s12249-019-1607-5

KEY WORDS

Search

Navigation