Skip to main content

Advertisement

SpringerLink
Log in

Formulation and Evaluation of Chitosan-PLGA Biocomposite Scaffolds Incorporated with Quercetin Liposomes Made by QbD Approach for Improved Healing of Oral Lesions

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

An Author Correction to this article was published on 17 August 2023

This article has been updated

Abstract

The current research aims to develop and evaluate chitosan-PLGA biocomposite scaffolds in combination with quercetin liposomes to accomplish the desired impact in oral lesions where pharmacotherapeutic agent treatment through circulation could only reach the low content at the target. Optimization of quercetin-loaded liposomes was carried out using 32 factorial design. The preparation of porous scaffolds comprising produced quercetin-loaded liposomes by thin-film method was carried out in the current study using a unique strategy combining solvent casting and gas foaming procedures. The prepared scaffolds were tested for physicochemical properties, in vitro quercetin release study, ex vivo drug permeation and retention research using goat mucosa, antibacterial activity, and cell migration studies on fibroblast L929 cell lines. Improved cell growth and migration were seen in the order control < liposomes < proposed system. The proposed system has been examined for its biological and physicochemical features, and it has the potential to be utilized as an efficient therapy for oral lesions.

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

Similar content being viewed by others

Data Availability

Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.

Change history

References

  1. Akash MS, Rehman K, Chen S. Polymeric-based particulate systems for delivery of therapeutic proteins. Pharm Dev Technol. 2016;21(3):367–78.

    Article  CAS  PubMed  Google Scholar 

  2. Amirchaghmaghi M, Delavarian Z, Iranshahi M, Shakeri MT, Mozafari PM, Mohammadpour AH, Farazi F, Iranshahy M. A randomized placebo-controlled double blind clinical trial of for treatment of oral lichen planus. J Dent Res Dent Clin Dent Prospects. 2015;9(1):23.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Attia DA, El-Say KM, Ramadan AA. Optimization and characterization of bioadhesive gastroretentive amoxicillin tablets using the mixture experimental design. J Appl Sci. 2008;4(11):1328–39.

    Google Scholar 

  4. Avachat AM, Gujar KN, Wagh KV. Development and evaluation of tamarind seed xyloglucan-based mucoadhesive buccal films of rizatriptan benzoate. Carbohydr Polym. 2013;91(2):537–42.

    Article  CAS  PubMed  Google Scholar 

  5. Bangham AD, Standish MM, Watkins JC. Diffussion of univalent ion across the lamellae of swollen phospholipids. J Mol Biol. 1995;13:238–52.

    Article  Google Scholar 

  6. Begum MYM, Osmani RA, Alqahtani A, Ghazwani M, Hani U, Ather H, Rahamathulla M, Siddiqua A. Development of stealth liposomal formulation of celecoxib: In-vitro and In-vivo evaluation. Plos One. 2022;17(4):e0264518.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Cascone MG, Barbani N, Cristallini C, Giusti P, Ciardelli G, Lazzeri L. Bioartificial polymeric materials based on polysaccharides. J Biomater Sci Polym Ed. 2001;12:267–81.

    Article  CAS  PubMed  Google Scholar 

  8. Chang JS, Chang KL, Hwang DF, Kong ZL. In-vitro cytotoxicitiy of silica nanoparticles at high concentrations strongly depends on the metabolic activity type of the cell line. Environ Sci Technol. 2007;41(6):2064–8.

    Article  CAS  PubMed  Google Scholar 

  9. Chen G, Kawazoe N, 3.1 - Preparation of polymer scaffolds by ice particulate method for tissue engineering, Editor(s): Mitsuhiro Ebara, Biomaterials Nanoarchitectonics, William Andrew Publishing, 2016, Pages 77-95, ISBN 9780323371278, https://doi.org/10.1016/B978-0-323-37127-8.00006-6.

  10. Coondoo A, Phiske M, Verma S, Lahiri K. Side-effects of topical steroids: a long overdue revisit. Indian Dermatol Online J. 2014;5(4):416–25.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Dash S, Murthy PN, Nath L, Chowdhury P. Kinetic modeling on drug release from controlled drug delivery systems. Acta Pol Pharm. 2010;67(3):217–23.

    CAS  PubMed  Google Scholar 

  12. Devi M, Kumar MS, Mahadevan N. Amphotericin-B loaded vesicular systems for the treatment of topical fungal infection. Int J Rec Adv Pharm Res. 2011;4:37–46.

    Google Scholar 

  13. Dhandayuthapani B, Yoshida Y, Maekawa T, Kumar DS. 2011. Polymeric scaffolds in tissue engineering application: a review. Int J Polym Sci. 290602. https://doi.org/10.1155/2011/290602.

  14. Doijad RC, Manvi FV, Rao VM, Patel PS. Buccoadhesive drug delivery system of isosorbide dinitrate: formulation and evaluation. Indian J Pharm Sci. 2006;68(6):744.

    Article  CAS  Google Scholar 

  15. Erjavec V, Pavlica Z, Sentjurc M, Petelin M. In vivo study of liposomes as drug carriers to oral mucosa using EPR oximetry. Int J Pharm. 2006;307(1):1–8.

    Article  CAS  PubMed  Google Scholar 

  16. Evans ND, Gentleman E, Polak JM. Scaffolds for stem cells. Mater Today. 2006;9(12):26–33.

    Article  CAS  Google Scholar 

  17. Garg T, Singh O, Arora S, Murthy RS. Scaffold: a novel carrier for cell and drug delivery. Crit Rev Ther Drug Carrier Sys. 2012;29(1):1–63.

    Article  CAS  Google Scholar 

  18. Gubernator J. Active methods of drug loading into liposomes: recent strategies for stable drug entrapment and increased in vivo activity. Expert Opin Drug Deliv. 2011;8(5):565–80.

    Article  CAS  PubMed  Google Scholar 

  19. Gupta V, Barupal AK, Ramteke S. Formulation development and In-vitro characterization of proliposomes for topical delivery of aceclofenac. Indian J Pharm Sci. 2008;70(6):768.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Hamdy AA, Ibrahem MA. Management of aphthous ulceration with topical quercetin: a randomized clinical trial. J Contemp Dent Prac. 2010;11(4):E009–16.

    Google Scholar 

  21. Hokmabad VR, Davaran S, Aghazadeh M, Rahbarghazi R, Salehi R, Ramazani A. Fabrication and characterization of novel ethyl cellulose-grafted-poly (ɛ-caprolactone)/alginate nanofibrous/macroporous scaffolds incorporated with nano-hydroxyapatite for bone tissue engineering. J Biomater Appl. 2019;33(8):1128–44.

    Article  CAS  PubMed  Google Scholar 

  22. Hamid AMS, Rehman K, Chen S. Natural and synthetic polymers as drug carriers for delivery of therapeutic proteins. Polym Rev. 2015;55(3):371–406.

    Article  Google Scholar 

  23. Kao TK, Ou YC, Raung SL, Lai CY, Liao SL, Chen CJ. Inhibition of nitric oxide production by quercetin in endotoxin/cytokine-stimulated microglia. Life Sci. 2010;86(9-10):315–21.

    Article  CAS  PubMed  Google Scholar 

  24. Kaur A, Kaur G. Mucoadhesive buccal patches based on interpolymer complexes of chitosan–pectin for delivery of carvedilol. Saudi Pharm J. 2012;20(1):21–7.

    Article  PubMed  Google Scholar 

  25. Lee EJ, Kasper FK, Mikos AG. Biomaterials for tissue engineering. Ann Biomed Eng. 2014;42(2):323-337. doi: 10.1007/s10439-013-0859-6

  26. Khojasteh A, Motamedian SR, Rad MR, Shahriari MH, Nadjmi N. Polymeric vs hydroxyapatite-based scaffolds on dental pulp stem cell proliferation and differentiation. World J Stem Cells. 2015;7(10):1215.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Jithendra PAM, Rajam T, Kalaivani AB, Mandal RC. Preparation and characterization of aloe vera blended collagen-chitosan composite scaffold for tissue engineering applications. ACS Appl Mater Interfaces. 2013;5(15):7291–308.

    Article  CAS  PubMed  Google Scholar 

  28. Lakhanpal P, Rai DK. Quercetin: a versatile flavonoid. Internet J Med Update. 2007;2(2):22–37.

    Google Scholar 

  29. Langer R, Acanti JP. Tissue engineering. Sci. 1993;260(5110):920–6.

    Article  CAS  Google Scholar 

  30. Liang C-C, Park AY, Guan J-L. In-vitro scratch assay: a convenient and inexpensive method for analysis of cell migration In-vitro. Nat Protoc. 2007;2:329–33.

    Article  CAS  PubMed  Google Scholar 

  31. Lin YJ, Yen CN, Hu YC, Wu YC, Liao CJ, Chu IM. Chondrocytes culture in three-dimensional porous alginate scaffolds enhanced cell proliferation, matrix synthesis and gene expression. J Biomed Mater Res A. 2009;88(1):23–33.

    Article  PubMed  Google Scholar 

  32. Ma L, Gao C, Mao Z, Zhou J, Shen J, Hu X, Han C. Collagen/chitosan porous scaffolds with improved biostability for skin tissue engineering. Biomaterials. 2003;24(26):4833–41.

    Article  CAS  PubMed  Google Scholar 

  33. Maherani B, Arab-Tehrany ER, Mozafari M, Gaiani C, Linder M. Liposomes: a review of manufacturing techniques and targeting strategies. Curr Nanosci. 2011;7(3):436–52.

    Article  CAS  Google Scholar 

  34. Mandal BB, Kundu SC. Cell proliferation and migration in silk fibroin 3D scaffolds. Biomaterials. 2009;30(15):2956–65.

    Article  CAS  PubMed  Google Scholar 

  35. Meng ZX, Zheng W, Zheng W, Li L, Li L, Zheng Y, Zheng Y. Fabrication, characterization and in vitro drug release behavior of electrospun PLGA/chitosan nanofibrous scaffold. Mat Chem Phy. 2011;125(3):606–11.

    Article  CAS  Google Scholar 

  36. Mostafa MA, Ibrahem MA. Management of aphthous ulceration with topical quercetin. Cairo Dent J. 2009;25(1):15.

    Google Scholar 

  37. Munot N, Kandekar U, Rikame C, Patil A, Sengupta P, Urooj S, Bilal A. Improved mucoadhesion, permeation and in-vitro anticancer potential of synthesized thiolated Acacia and Karaya gum combination: a systematic study. Molecules. 2022b;27(20):6829.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Munot N, Kandekar U, Giram PS, Khot K, Patil A, Cavalu S. A comparative study of quercetin-loaded nanocochleates and liposomes: formulation, characterization, assessment of degradation and in-vitro anticancer potential. Pharmaceutics. 2022a;14(8):1601.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Nguyen TLA, Bhattacharya D. Antimicrobial activity of quercetin: an approach to its mechanistic principle. Molecules. 2022;27(8):2494.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Paderni C, Compilato D, Giannola LI, Campisi G. Oral local drug delivery and new perspectives in oral drug formulation. Oral Surg. Oral Med. Oral Pathol. Oral Radiol. 2012;114(3):e25–34.

    Article  Google Scholar 

  41. Pan Z, Ding J. Poly(lactide-co-glycolide) porous scaffolds for tissue engineering and regenerative medicine. Interface Focus. 2012;2(3):366–77.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Patel V, Liu F, Brown MB. Advances in oral transmucosal drug delivery. J. Control Release. 2011;153(2):106–16.

    Article  CAS  PubMed  Google Scholar 

  43. Patel VF, Liu F, Brown MB. Modeling the oral cavity: in-vitro and in vivo evaluations of buccal drug delivery systems. J Control Release. 2012;161(3):746–56.

    Article  CAS  PubMed  Google Scholar 

  44. Patil PS, Salunkhe VR, Bhinge SD, Patil SB, Kumbhar BV. Formulation optimization and evaluation of glycyrrhetinic acid loaded PLARosome using factorial design: in-vitro anti-ulcer activity and in silico PASS prediction. J Indian Chem Soc. 2021;98:100199.

    Article  CAS  Google Scholar 

  45. Patil A, Munot N, Patwekar M, Patwekar F, Ahmad I, Alraey Y, Alghamdi S, Kabrah A, Dablool AS, Islam F. Encapsulation of lactic acid bacteria by lyophilisation with its effects on viability and adhesion properties. Evid Based Complement Altern Med. 2022;4651194:9.

    Google Scholar 

  46. Pawar A, Bothiraja C, Shaikh K, Mali A. An insight into cochleates, a potential drug delivery system. RSC Adv. 2015;5(99):81188–202.

    Article  CAS  Google Scholar 

  47. Peter M, Ganesh N, Selvamurugan N, Nair SV, Furuike T, Tamura H, Jayakumar R. Preparation and characterization of chitosan–gelatin/nanohydroxyapatite composite scaffolds for tissue engineering applications. Carbohydr Polym. 2010;80(3):687–94.

    Article  CAS  Google Scholar 

  48. Salunkhe VR, Patil PS, Wadkar GH, Bhinge SD. Herbal liposomes: natural network for targeted drug delivery system. Int J Pharm Res. 2021;33(29B):31–41.

    Article  Google Scholar 

  49. Sarkar N, Bose S. Liposome-encapsulated curcumin-loaded 3D printed scaffold for bone tissue engineering. ACS Appl Mater Interfaces. 2019;11(19):17184–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Shirvan AR, Bashari A, Hemmatinejad. New insight into the fabrication of smart mucoadhesive buccal patches as a novel controlled-drug delivery system. Eur Polym J. 2019;119:541–50.

    Article  Google Scholar 

  51. Vissers CA, Harvestine JN, Leach JK. Pore size regulates mesenchymal stem cell response to Bioglass-loaded composite scaffolds. J Mat Chem B. 2015;3(44):8650–8.

    Article  CAS  Google Scholar 

  52. Yardimci G, Kutlubay Z, Engin B, Tuzun Y. Precancerous lesions of oral mucosa. World J Clin Cases. 2014;2(12):866–72.

    Article  PubMed  PubMed Central  Google Scholar 

  53. Yu ES, Min HJ, An SY, Won HY, Hong JH, Hwang ES. Regulatory mechanisms of IL-2 and IFNγ suppression by quercetin in T helper cells. Biochem Pharmacol. 2008;76(1):70–88.

    Article  CAS  PubMed  Google Scholar 

  54. Wijetunge SS, Wen J, Yeh CK, Sun Y. Lectin-conjugated liposomes as biocompatible, bioadhesive drug carriers for the management of oral ulcerative lesions. ACS Appl Bio Mater. 2018;1(5):1487–895.

    Article  CAS  PubMed  Google Scholar 

  55. Zakizadeh M, Nabavi SF, Nabavi SM, Ebrahimzadeh MA. In-vitro antioxidant activity of flower, seed and leaves of Alcea hyrcana Grossh. Eur Rev Med Pharmacol Sci. 2011;15(4):406–12.

    CAS  PubMed  Google Scholar 

  56. Zhang H, Liu X, Yang M, Zhu L. Silk fibroin/sodium alginate composite nano-fibrous scaffold prepared through thermally induced phase-separation (TIPS) method for biomedical applications. Mat Sci Eng C. 2015;55:8–13.

    Article  Google Scholar 

  57. Zhang J, Liu H, Ding JX, Wu J, Zhuang XL, Chen XS, Wang JC, Yin JB, Li ZM. High-pressure compression-molded porous resorbable polymer/hydroxyapatite composite scaffold for cranial bone regeneration. ACS Biomater Sci Eng. 2016a;2(9):1471–82.

    Article  CAS  PubMed  Google Scholar 

  58. Zhang J, Yang SG, Ding JX, Li ZM. Tailor-made poly (l-lactide)/poly (lactide-co-glycolide)/hydroxyapatite composite scaffolds prepared via high-pressure compression molding/salt leaching. RSC Adv. 2016b;6(53):47418–26.

    Article  CAS  Google Scholar 

  59. Zhu CT, Xu YQ, Shi J, Li J, Ding J. Liposome combined porous β-TCP scaffold: preparation, characterization, and anti-biofilm activity. Drug Deliv. 2010;17(6):391–8.

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

This study was funded by Savitribai Phule Pune University under Aspire Research Mentorship Grant (Grant No. 18TEC001157).

Author information

Authors and Affiliations

  1. Technical Lead, HCL Technologies, Chennai, Tamil Nadu, 600058, India

    Neha Manish Munot

  2. Department of Pharmaceutics, STES’s Smt. Kashibai Navale College of Pharmacy, Kondhwa (Bk), Affiliated to Savitribai Phule Pune University, Pune, 411048, India

    Yashwant Dattatraya Shinde

  3. Maliba Pharmacy College, Bardoli, Gujarat, 394350, India

    Pranav Shah

  4. Department of Pharmaceutics, D Y Patil College of Pharmacy, Kolhapur, 416006, India

    Abhinandan Patil

  5. Department of Pharmacology, Dr. Shivajirao Kadam College of Pharmacy, Kasbe Digraj, Maharashtra, MS, 416305, India

    Sandeep B. Patil

  6. Department of Pharmaceutical Chemistry, Rajarambapu College of Pharmacy, Kasegaon, MS, 415404, India

    Somnath D. Bhinge

Authors
  1. Neha Manish Munot
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yashwant Dattatraya Shinde
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Pranav Shah
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Abhinandan Patil
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Sandeep B. Patil
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Somnath D. Bhinge
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors contributed to the study’s conception and design. The first draft of the manuscript was written by Neha Munot, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Somnath D. Bhinge.

Ethics declarations

Ethics Approval and Consent to Participate

Not applicable

Consent for Publication

Not applicable.

Competing Interests

The authors declare no competing interests.

Additional information

Publisher’s Note

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

Highlights

• In this research, the authors have successfully prepared porous biocomposite scaffolds loaded with quercetin liposomes.

• Liposomes is novel drug delivery system to achieve target-specific action along with other numerous benefits than conventional drug delivery system.

• Moreover, authors have successfully characterized prepared porous biocomposite scaffolds loaded with quercetin liposomes using advanced tools.

• The authors have explored the improved healing of oral lesions and antibacterial activity of porous biocomposite scaffolds loaded with quercetin liposomes.

The original article has been updated to correct Dr. Pranav Shah's affiliation.

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.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Munot, N.M., Shinde, Y.D., Shah, P. et al. Formulation and Evaluation of Chitosan-PLGA Biocomposite Scaffolds Incorporated with Quercetin Liposomes Made by QbD Approach for Improved Healing of Oral Lesions. AAPS PharmSciTech 24, 147 (2023). https://doi.org/10.1208/s12249-023-02584-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1208/s12249-023-02584-x

Keywords

Search

Navigation