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Formulation of Chitosan-Coated Piperine NLCs: Optimization, In Vitro Characterization, and In Vivo Preclinical Assessment

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Abstract

In the present research work, surface-modified nanostructured lipid carriers (NLCs) with chitosan (CH) were prepared to improve the therapeutic efficacy of piperine (PP). NLCs were developed and optimized (CH-PP-NLCs-opt) by design expert software and the selected NLCs surface was coated with chitosan (0.2% w/v). CH-PP-NLCs-opt have shown a particle size of 149.34 ± 4.54 nm and entrapment efficiency of 80.65 ± 1.23%. The results of the solid-state characterization study exhibited that PP enclosed in lipids and present amorphous form. It might be due to the nanoparticle size of NLCs. The drug release study revealed PP-NLCs-opt and CH-PP-NLCs-opt exhibited significant (P < 0.05) difference in PP release (88.87 ± 5.23% and 76.34 ± 4.54%) as compared to pure PP (19.02 ± 2.87%). CH-PP-NLCs-opt exhibited strong bioadhesion than PP-NLCs-opt which has a positive influence the drug permeation and absorption. CH-PP-NLCs-opt showed higher permeation (1083.34 ± 34.15 μg/ cm2) than pure PP (106.65 ± 15.44 μg/cm2) and PP-NLCs-opt (732.45 ± 28.56 μg/ cm2). The significantly enhanced bioavailability of PP was observed from CH-PP-NLCs-opt (3.76- and 1.21-fold) than PP-dispersion and PP-NLCs-opt. The diabetes was induced in rats by a single intraperitoneal administration of streptozotocin (STZ, 40 mg/kg, citrate buffer pH 4.5), and results revealed that PP-NLCs-opt and CH-PP-NLCs-opt reduce the blood glucose level (28.26% and 36.52% respectively) as compared to PP-dispersion (10.87%). It also helps to maintain the altered biochemical parameters. In conclusion, CH-PP-NLC can be a novel oral nanocarrier for the management of diabetes.

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References

  1. Wu Y, Ding Y, Tanaka Y, Zhang W. Risk factors contributing to type 2 diabetes and recent advances in the treatment and prevention. Int J Med Sci. 2014;11(11):1185–200.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Rana S, Kumar S, Rathore N, Padwad Y, Bhushan S. Nutrigenomics and its impact on life style associated metabolic diseases. Curr Genomics. 2016;17(3):261–78.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Samarakoon DNAW, Uluwaduge DI, Siriwardhene MA. Mechanisms of action of Sri Lankan herbal medicines used in the treatment of diabetes: a review. J Integr Med. 2020;18(1):14–20.

    Article  PubMed  Google Scholar 

  4. Gupta S, Kesarla R, Omri A. Formulation strategies to improve the bioavailability of poorly absorbed drugs with special emphasis on self-emulsifying systems. ISRN Pharm. 2013;2013:1–16.

    Google Scholar 

  5. Jarald E, Joshi SB, Jain DC. Diabetes and herbal medicines. Iran J Pharmacol Ther. 2008;7(1):97–106.

    CAS  Google Scholar 

  6. Stojanović-Radić Z, Pejčić M, Dimitrijević M, Aleksić A, Anil Kumar NV, Salehi B, et al. Piperine—a major principle of black pepper: a review of its bioactivity and studies. Appl Sci. 2019;9(20):1–29.

    Article  CAS  Google Scholar 

  7. Gorgani L, Mohammadi M, Najafpour GD, Nikzad M. Piperine—the bioactive compound of black pepper: from isolation to medicinal formulations. Compr Rev Food Sci Food Saf. 2017;16(1):124–40.

    Article  CAS  PubMed  Google Scholar 

  8. Kharbanda C, Alam MS, Hamid H, Javed K, Bano S, Ali Y, et al. Novel Piperine derivatives with antidiabetic effect as PPAR-γ agonists. Chem Biol Drug Des. 2016;1:354–62.

    Article  CAS  Google Scholar 

  9. Panahi Y, Khalili N, Hosseini MS, Abbasinazari M, Sahebkar A. Lipid-modifying effects of adjunctive therapy with curcuminoids-piperine combination in patients with metabolic syndrome: results of a randomized controlled trial. Complement Ther Med. 2014;22(5):851–7.

    Article  PubMed  Google Scholar 

  10. Kumar S, Sharma S, Vasudeva N. Screening of antidiabetic and antihyperlipidemic potential of oil from Piper longum and piperine with their possible mechanism. Expert Opin Pharmacother. 2013;14(13):1723–36.

    Article  CAS  PubMed  Google Scholar 

  11. Boddupalli BM, Masana P, Anisetti RN, Kallem SV, Madipoju B. Formulation and evaluation of Pioglitazone loaded Bovine serum albumin nanoparticles along with Piperine. Drug Invent Today. 2013;5(3):212–5.

    Article  CAS  Google Scholar 

  12. Abdel-Daim MM, Sayed AA, Abdeen A, Aleya L, Ali D, Alkahtane AA, et al. Piperine enhances the antioxidant and anti-inflammatory activities of thymoquinone against microcystin-LR-induced hepatotoxicity and neurotoxicity in mice. Oxidative Med Cell Longev. 2019;2019:1–10.

  13. Doucette CD, Hilchie AL, Liwski R, Hoskin DW. Piperine, a dietary phytochemical, inhibits angiogenesis. J Nutr Biochem. 2013;24(1):231–9.

    Article  CAS  PubMed  Google Scholar 

  14. Shao B, Cui C, Ji H, Tang J, Wang Z, Liu H, et al. Enhanced oral bioavailability of piperine by self-emulsifying drug delivery systems: In vitro, in vivo and in situ intestinal permeability studies. Drug Deliv. 2015;22(6):740–7.

  15. Ren T, Hu M, Cheng Y, Shek TL, Xiao M, Ho NJ, et al. Piperine-loaded nanoparticles with enhanced dissolution and oral bioavailability for epilepsy control. Eur J Pharm Sci. 2019;137:104988.

  16. Alshehri S, Imam SS, Hussain A, Altamimi MA. Formulation of piperine ternary inclusion complex using β CD and HPMC: physicochemical characterization, molecular docking, and antimicrobial testing. Processes. 2020;1450(8):1–15.

  17. Lingli Q. Advance on delivery nanocarriers of piperine: Nanoparticles. E3S Web Conf. 2019;131:3–6.

    Article  CAS  Google Scholar 

  18. Izgelov D, Cherniakov I, Aldouby Bier G, Domb AJ, Hoffman A. The effect of piperine pro-nano lipospheres on direct intestinal phase II metabolism: the Raloxifene paradigm of enhanced oral bioavailability. Mol Pharm. 2018;15(4):1548–55.

    Article  CAS  PubMed  Google Scholar 

  19. Pachauri M, Gupta ED, Ghosh PC. Piperine loaded PEG-PLGA nanoparticles: Preparation, characterization and targeted delivery for adjuvant breast cancer chemotherapy. J Drug Deliv Sci Technol. 2015;29:269–82.

    Article  CAS  Google Scholar 

  20. Al-Heibshy FNS, Başaran E, Arslan R, Öztürk N, Erol K, Demirel M. Physicochemical characterization and pharmacokinetic evaluation of rosuvastatin calcium incorporated solid lipid nanoparticles. Int J Pharm. 2020;578:119106.

    Article  CAS  PubMed  Google Scholar 

  21. Elmowafy M, Ibrahim HM, Ahmed MA, Shalaby K, Salama A, Hefesha H. Atorvastatin-loaded nanostructured lipid carriers (Nlcs): strategy to overcome oral delivery drawbacks. Drug Deliv. 2017;24(1):932–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Chauhan I, Yasir M, Verma M, Singh AP. Nanostructured lipid carriers: a groundbreaking approach for transdermal drug delivery. Adv Pharm Bull. 2020;10(2):150–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Ameeduzzafar, Ali J, Bhatnagar A, Kumar N, Ali A. Chitosan nanoparticles amplify the ocular hypotensive effect of cateolol in rabbits. Int J Biol Macromol. 2014;65:479–91.

    Article  CAS  PubMed  Google Scholar 

  24. Bin-Jumah M, Gilani SJ, Jahangir MA, Zafar A, Alshehri S, Yasir M, et al. Clarithromycin-loaded ocular chitosan nanoparticle: formulation, optimization, characterization, ocular irritation, and antimicrobial activity. Int J Nanomedicine. 2020;15:7861–75.

  25. Shoueir KR, El-Desouky N, Rashad MM, Ahmed MK, Janowska I, El-Kemary M. Chitosan based-nanoparticles and nanocapsules: overview, physicochemical features, applications of a nanofibrous scaffold, and bioprinting. Int J Biol Macromol. 2021;167:1176–1197.

  26. Rehman S, Nabi B, Baboota S, Ali J. Tailoring lipid nanoconstructs for the oral delivery of paliperidone: formulation, optimization and in vitro evaluation. Chem Phys Lipids. 2021;234:105005.

    Article  CAS  PubMed  Google Scholar 

  27. Yasir M, Sara UVS. Solid lipid nanoparticles for nose to brain delivery of haloperidol: In vitro drug release and pharmacokinetics evaluation. Acta Pharm Sin B. 2014;4(6):454–63.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Walimbe CA, More SS, Walawalkar RU, Shah RR, Ghodake D. Optimisation of nanostructured lipid carriers of Ritonavir. Inven Rapid NDDS. 2012;4:4–11.

    Google Scholar 

  29. Yasir M, Vir Singh Sara U, Som I, Gaur P, Singh M, Ameeduzzafar. Nose to brain drug delivery: a novel approach through solid lipid nanoparticles. Curr Nanomedicine. 2016;6(2):105–32.

    Article  CAS  Google Scholar 

  30. Jazuli I, Annu NB, Moolakkadath T, Alam T, Baboota S, et al. Optimization of nanostructured lipid carriers of lurasidone hydrochloride using Box-Behnken design for brain targeting: in vitro and in vivo studies. J Pharm Sci. 2019;108(9):3082–90.

    Article  CAS  PubMed  Google Scholar 

  31. Ameeduzzafar,  Qumber M, Alruwaili NK, Bukhari SNA, Alharbi KS, Imam SS, et al. BBD-based development of itraconazole loaded nanostructured lipid carrier for topical delivery: in vitro evaluation and antimicrobial assessment. J Pharm Innov. 2021;16:85–98.

  32. Ameeduzzafar, Khan N, Alruwaili NK, Bukhari SNA, Alsuwayt B, Afzal M, et al. Improvement of ocular efficacy of levofloxacin by bioadhesive chitosan coated PLGA nanoparticles: Box-behnken design, in-vitro characterization, antibacterial evaluation and scintigraphy study. Iran J Pharm Res. 2020;19(1):292–311.

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Yasir M, Sara UVS. Preparation and optimization of haloperidol loaded solid lipid nanoparticles by Box–Behnken design. J Pharm Res. 2013;7(6):551–8.

    CAS  Google Scholar 

  34. Ameeduzzafar, Alruwaili NK, Imam SS, Alotaibi NH, Alhakamy NA, Alharbi KS, et al. Formulation of chitosan polymeric vesicles of ciprofloxacin for ocular delivery: Box-Behnken optimization, in vitro characterization, HET-CAM irritation, and antimicrobial assessment. AAPS PharmSciTech. 2020;21(5):167.

  35. Pyo YC, Tran P, Kim DH, Park JS. Chitosan-coated nanostructured lipid carriers of fenofibrate with enhanced oral bioavailability and efficacy. Colloids Surf B: Biointerfaces. 2020;196:111331.

    Article  CAS  PubMed  Google Scholar 

  36. Gilani SJ, Bin-Jumah M, Rizwanullah M, Imam SS, Imtiyaz K, Alshehri S, et al. Chitosan coated luteolin nanostructured lipid carriers: optimization, in vitro-ex vivo assessments and cytotoxicity study in breast cancer cells. Coatings. 2021;11(2):1–16.

    Article  CAS  Google Scholar 

  37. Ameeduzzafar, Ali J, Khan N, Ali A. Development and optimization of carteolol loaded carboxymethyl tamarind kernel polysaccharide nanoparticles for ophthalmic delivery: box-behnken design, in vitro, ex vivo assessment. Sci Adv Mater. 2014;6(1):63–75.

    Article  CAS  Google Scholar 

  38. Yeo PL, Lim CL, Chye SM, Ling APK, Koh RY. Niosomes: a review of their structure, properties, methods of preparation, and medical applications. Asian Biomed. 2017;11(4):301–13.

    Article  Google Scholar 

  39. Santosh MK, Shaila D, Rajyalakshmi I, Rao IS. RP - HPLC Method for determination of piperine from piper longum Linn. and Piper nigrum Linn. E-Journal Chem. 2005;2(2):131–5.

    Article  Google Scholar 

  40. Yasir M, Chauhan I, Zafar A, Verma M, Noorulla KM, Tura AJ, et al. Buspirone loaded solid lipid nanoparticles for amplification of nose to brain efficacy: Formulation development, optimization by Box-Behnken design, in-vitro characterization and in-vivo biological evaluation. J Drug Deliv Sci Technol. 2020;102164.

  41. El Rabey HA, Al-Seeni MN, Bakhashwain AS. The antidiabetic activity of nigella sativa and propolis on streptozotocin-induced diabetes and diabetic nephropathy in male rats. Evidence-based Complement Altern Med. 2017;2017:1–14.

    Article  Google Scholar 

  42. Khan S, Shaharyar M, Fazil M, Baboota S, Ali J. Tacrolimus-loaded nanostructured lipid carriers for oral delivery—optimization of production and characterization. Eur J Pharm Biopharm. 2016;108:277–88.

    Article  CAS  PubMed  Google Scholar 

  43. Poonia N, Kharb R, Lather V, Pandita D. Nanostructured lipid carriers: versatile oral delivery vehicle. Futur Sci OA. 2016;2(3):FSO135.

  44. Zafar A. Development of oral lipid based nano-formulation of dapagliflozin: optimization, in vitro characterization and ex vivo intestinal permeation study. J Oleo Sci. 2020;69(11):1389–401.

    Article  CAS  PubMed  Google Scholar 

  45. Alam T, Khan S, Gaba B, Haider MF, Baboota S, Ali J. Adaptation of quality by design-based development of isradipine nanostructured–lipid carrier and its evaluation for in vitro gut permeation and in vivo solubilization fate. J Pharm Sci. 2018;107(11):2914–26.

    Article  CAS  PubMed  Google Scholar 

  46. Elmowafy M, Alruwaili NK, Shalaby K, Alharbi KS, Altowayan WM, Ahmed N, et al. Long-acting paliperidone parenteral formulations based on polycaprolactone nanoparticles; the influence of stabilizer and chitosan on in vitro release, protein adsorption, and cytotoxicity. Pharmaceutics. 2020;12(2).

  47. Uprit S, Kumar Sahu R, Roy A, Pare A. Preparation and characterization of minoxidil loaded nanostructured lipid carrier gel for effective treatment of alopecia. Saudi Pharm J. 2013;21(4):379–85.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Shamma RN, Aburahma MH. Follicular delivery of spironolactone via nanostructured lipid carriers for management of alopecia. Int J Nanomedicine. 2014;9(1):5449–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Eid RK, Ashour DS, Essa EA, El Maghraby GM, Arafa MF. Chitosan coated nanostructured lipid carriers for enhanced in vivo efficacy of albendazole against Trichinella spiralis. Carbohydr Polym. 2020;232:115826.

  50. Khan A, Iqbal Z, Khadra I, Ahmad L, Khan A, Khan MI, et al. Simultaneous determination of domperidone and Itopride in pharmaceuticals and human plasma using RP-HPLC/UV detection: Method development, validation and application of the method in in-vivo evaluation of fast dispersible tablets. J Pharm Biomed Anal. 2016;121:6–12.

  51. Naik A, Pechtold LARM, Potts RO, Guy RH. Mechanism of oleic acid-induced skin penetration enhancement in vivo in humans. J Control Release. 1995;37(3):299–306.

    Article  CAS  Google Scholar 

  52. Thatipamula RP, Palem CR, Gannu R, Mudragada S, Yamsani MR. Formulation and in vitro characterization of domperidone loaded solid lipid nanoparticles and nanostructured lipid carriers. DARU, J Pharm Sci. 2011;19(1):23–32.

    CAS  Google Scholar 

  53. Li M, Si L, Pan H, Rabba AK, Yan F, Qiu J, et al. Excipients enhance intestinal absorption of ganciclovir by P-gp inhibition:assessed in vitro by everted gut sac and in situ by improved intestinal perfusion. Int J Pharm. 2011;403(1–2):37–45.

  54. Hallan SS, Kaur P, Kaur V, Mishra N, Vaidya B. Lipid polymer hybrid as emerging tool in nanocarriers for oral drug delivery. Artif Cells Nanomed Biotechnol. 2016;44(1):334–49.

    Article  CAS  PubMed  Google Scholar 

  55. Shah P, Chavda K, Vyas B, Patel S. Formulation development of linagliptin solid lipid nanoparticles for oral bioavailability enhancement: role of P-gp inhibition. Drug Deliv Transl Res. 2021;11(3):1166-1185.

  56. Yasir M, Gaur PK, Puri D, Preeti S, Kumar SS. Solid lipid nanoparticles approach for lymphatic targeting through intraduodenal delivery of quetiapine fumarate. Curr Drug Deliv. 2017;15(6):818–28.

    Article  CAS  Google Scholar 

  57. Shah NV, Seth AK, Balaraman R, Aundhia CJ, Maheshwari RA, Parmar GR. Nanostructured lipid carriers for oral bioavailability enhancement of raloxifene: design and in vivo study. J Adv Res. 2016;7(3):423–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

The authors extend their appreciation to the Deanship of Scientific Research, Jouf University for funding this work through research grant no (DSR 2020-04-488).

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Authors and Affiliations

  1. Department of Pharmaceutics, College of Pharmacy, Jouf University, Sakaka, Aljouf Region, 72341, Saudi Arabia

    Ameeduzzafar Zafar, Nabil K. Alruwaili, Omar Awad Alsaidan & Mohammed Elmowafy

  2. Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia

    Syed Sarim Imam

  3. Department of Pharmacology, College of Pharmacy, Jouf University, Sakaka, Aljouf Region, 72341, Saudi Arabia

    Khalid Saad Alharbi

  4. Department of Pharmacy, College of Health Science, Arsi University, Asella, Ethiopia

    Mohd Yasir

  5. Department of Biology, College of Science, Jouf University, Sakaka, Aljouf Region, Saudi Arabia

    Elshaer F. Mohammed

  6. Department of Clinical Laboratories Sciences, College of Applied Medical Sciences, Jouf University, Sakaka, Aljouf Region, Saudi Arabia

    Ziad H. Al-Oanzi

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  1. Ameeduzzafar Zafar
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  2. Nabil K. Alruwaili
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Correspondence to Ameeduzzafar Zafar.

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The protocol of the study was approved by the Institutional Animal Ethical Committee (IAEC), Jouf University, Aljouf, KSA (approval number=18-5-42).

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Zafar, A., Alruwaili, N.K., Imam, S.S. et al. Formulation of Chitosan-Coated Piperine NLCs: Optimization, In Vitro Characterization, and In Vivo Preclinical Assessment. AAPS PharmSciTech 22, 231 (2021). https://doi.org/10.1208/s12249-021-02098-4

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