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Current Nanomaterials

Author(s): Dipthi Shree*, Chinam N. Patra, Debashish Ghose, Goutam K. Jena, Biswa M. Sahoo, Kahnu C. Panigrahi and Jammula Sruti

DOI: 10.2174/2405461507666220418113115

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Cinacalcet HCl-Loaded PLGA Nanoparticles Using the Porous Carrier

Page: [90 - 100] Pages: 11

  • * (Excluding Mailing and Handling)

Abstract

Background: Cinacalcet HCl is a calcimimetic, BCS class IV drug with low oral bioavailability. Polymeric nanoparticles are widely used as biomaterials owing to their biocompatibility, biodegradability, varied structures, low toxicity, and simple and easy formulation process.

Objective: The aim of the study was to enhance the oral bioavailability of poorly water-soluble drug, i.e., cinacalcet HCl, by using a suitable particulate nanocarrier system, i.e., polymeric nanoparticles.

Methods: Biodegradable Cinacalcet HCl (CH)-loaded poly (lactic-co-glycolic acid) (PLGA) nanoparticles were prepared by nanoprecipitation method using Poloxamer-188 as a stabilizer. The experimental parameters, like polymer concentration, stabilizer concentration, temperature, and RPM speed, were optimized. An optimized polymeric nanoparticle formulation PNP (F8) was solidified by adsorption on the porous carrier sylysia 350.

Results: PNP (F8) exhibited a particle size of 155 nm with low PDI (0.231) and high zeta potential (- 21.3 mV). In vitro diffusion study revealed sustained release of CH for 24 h for both PNP (F8) and solidified PNP (F8). Pharmacokinetics after oral administration of PNP (F8) and solidified PNP (F8) exhibited a 5-fold increase in bioavailability. Thus, both PNP (F8) and solidified PNP (F8) showed significant improvement in oral bioavailability.

Conclusion: Adsorption of polymeric nanoparticles onto porous carriers like sylysia 350 can be considered as a promising approach for long-term stability.

Keywords: Sylysia 350, nanoprecipitation, P-XRD, probe sonication, calcium-sensing receptor, cinacalcet HCl.

Graphical Abstract

[1]
Rothe HM, Liangos O, Biggar P, Petermann A, Ketteler M. Cinacalcet treatment of primary hyperparathyroidism. Int J Endocrinol 2011; 2011: 415719.
[http://dx.doi.org/10.1155/2011/415719] [PMID: 21461394]
[2]
Lindberg JS, Culleton B, Wong G, et al. Cinacalcet HCl, an oral calcimimetic agent for the treatment of secondary hyperparathyroidism in hemodialysis and peritoneal dialysis: A randomized, double-blind, multicenter study. J Am Soc Nephrol 2005; 16(3): 800-7.
[http://dx.doi.org/10.1681/ASN.2004060512] [PMID: 15689407]
[3]
Cunningham J, Danese M, Olson K, Klassen P, Chertow GM. Effects of the calcimimetic cinacalcet HCl on cardiovascular disease, fracture, and health-related quality of life in secondary hyperparathyroidism. Kidney Int 2005; 68(4): 1793-800.
[http://dx.doi.org/10.1111/j.1523-1755.2005.00596.x] [PMID: 16164656]
[4]
Cinacalcet hydrochloride. Available from: https://pubchem.ncbi.nlm.nih.gov/compound/Cinacalcet-hydrochloride
[5]
Europa.eu. Available from: https://www.ema.europa.eu/en/docu- ments/assessment-report/cinacalcet-accordpharma-epar-public-assessment-report-en
[6]
Xu X, Chen G, Li Y, Wang J, Yin J, Ren L. Enhanced dissolution and oral bioavailbility of cinacalcet hydrochlorde nanocrystals with no food effect. Nanotechnology 2019; 30(5): 055102.
[http://dx.doi.org/10.1088/1361-6528/aaef46] [PMID: 30511665]
[7]
Bennet D, Kim S. Polymer nanoparticles for smart drug delivery. In: Application of nanotechnology in drug delivery. Intech Open Science 2014; pp. 257-310.
[8]
Anagnostou K, Stylianakis M, Michaleas S, Skouras A. Biodegradable nanomaterial. In: Nanomater for Clin. Appl 2020; pp. 123-57.
[9]
Madkour LH. Nanoparticle and polymeric nanoparticle-based targeted drug delivery systems. In: Nucleic acids as gene anticancer drug delivery therapy. Academic Press: Cambridge, MA, USA 2019; pp. 191-240.
[10]
Din FU, Aman W, Ullah I, et al. Effective use of nanocarriers as drug delivery systems for the treatment of selected tumors. Int J Nanomedicine 2017; 12: 7291-309.
[http://dx.doi.org/10.2147/IJN.S146315] [PMID: 29042776]
[11]
Banik BL, Fattahi P, Brown JL. Polymeric nanoparticles: The future of nanomedicine. Wiley Interdiscip Rev Nanomed Nanobiotechnol 2016; 8(2): 271-99.
[http://dx.doi.org/10.1002/wnan.1364] [PMID: 26314803]
[12]
Begines B, Ortiz T, Pérez-Aranda M, et al. Polymeric nanoparticles for drug delivery: Recent developments and future prospects. Nanomaterials 2020; 10(7): 1403.
[http://dx.doi.org/10.3390/nano10071403] [PMID: 32707641]
[13]
des Rieux A, Fievez V, Garinot M, Schneider YJ, Préat V. Nanoparticles as potential oral delivery systems of proteins and vaccines: A mechanistic approach. J Control Release 2006; 116(1): 1-27.
[http://dx.doi.org/10.1016/j.jconrel.2006.08.013] [PMID: 17050027]
[14]
Liechty WB, Kryscio DR, Slaughter BV, Peppas NA. Polymers for drug delivery systems. Annu Rev Chem Biomol Eng 2010; 1(1): 149-73.
[http://dx.doi.org/10.1146/annurev-chembioeng-073009-100847] [PMID: 22432577]
[15]
Kumari A, Yadav SK, Yadav SC. Biodegradable polymeric nanoparticles based drug delivery systems. Colloids Surf B Biointerfaces 2010; 75(1): 1-18.
[http://dx.doi.org/10.1016/j.colsurfb.2009.09.001] [PMID: 19782542]
[16]
Sung YK, Kim SW. Recent advances in polymeric drug delivery systems. Biomater Res 2020; 24(1): 12.
[http://dx.doi.org/10.1186/s40824-020-00190-7] [PMID: 32537239]
[17]
Nimesh S. Poly (D, L-lactide-co-glycolide)-based nanoparticles Gene Therapy Potential Applications of Nanotechnology Cambridge Woodhead Publishing. 2013; pp. 309-29.
[18]
Hua Y, Su Y, Zhang H, et al. Poly(lactic-co-glycolic acid) microsphere production based on quality by design: A review. Drug Deliv 2021; 28(1): 1342-55.
[http://dx.doi.org/10.1080/10717544.2021.1943056] [PMID: 34180769]
[19]
Ahuja G, Pathak K. Porous carriers for controlled/modulated drug delivery. Indian J Pharm Sci 2009; 71(6): 599-607.
[http://dx.doi.org/10.4103/0250-474X.59540] [PMID: 20376211]
[20]
Planinšek O. Kovačič B, Vrečer F. Carvedilol dissolution improvement by preparation of solid dispersions with porous silica. Int J Pharm 2011; 406(1-2): 41-8.
[http://dx.doi.org/10.1016/j.ijpharm.2010.12.035] [PMID: 21219991]
[21]
Segall AI. Preformulation: The use of FTIR in compatibility studies. JIAPS 2019; 4(3): 1-6.
[22]
Kosy O, Subramanian L, Thomas S. Differential scanning calorimetry in nanoscience and nanotechnology. In: Thermal and Rheological Measurement Techniques for Nanomaterials Characterization. 2017; pp. 109-22.
[23]
Panigrahi KC, Patra CN, Rao MEB. Quality by design enabled development of oral self-nanoemulsifying drug delivery system of a novel calcimimetic cinacalcet HCI using a porous carrier: In-vitro and in-vivo characterisation. AAPS PharmSciTech 2019; 20(5): 216.
[http://dx.doi.org/10.1208/s12249-019-1411-2] [PMID: 31172322]
[24]
Lancheros R, Guerrero CA, Godoy-Silva RD. Improvement of N-Acetylcysteine loaded in PLGA nanoparticles by nanoprecipitation method. J Nanotechnol 2018; 4: 1-11.
[http://dx.doi.org/10.1155/2018/3620373]
[25]
Jena GK, Patra CN, Dixit PK. Cytotoxicity and pharmacokinetic studies of PLGA based capecitabine loaded nanoparticles. Indian J Pharm Educ Res 2020; 54(2): 349-56.
[http://dx.doi.org/10.5530/ijper.54.2.40]
[26]
Gaikwad VL, Choudhari PB, Bhatia NM, Bhatia MS. Characterization of pharmaceutical nanocarriers: In-vitro and in-vivo studies. In: Nanomaterials for Drug Delivery and Therapy. 2019; pp. 33-58.
[http://dx.doi.org/10.1016/B978-0-12-816505-8.00016-3]
[27]
Salatin S, Barar J, Barzegar-Jalali M, Adibkia K, Kiafar F, Jelvehgari M. Development of a nanoprecipitation method for the entrapment of a very water soluble drug into Eudragit RL nanoparticles. Res Pharm Sci 2017; 12(1): 1-14.
[http://dx.doi.org/10.4103/1735-5362.199041] [PMID: 28255308]
[28]
Buhr E, Senftleben N, Klein T, et al. Characterization of nanoparticles by scanning electron microscopy in transmission mode Measur Sci Technol 20(8) 084025.
[http://dx.doi.org/10.1088/0957-0233/20/8/084025]
[29]
Dodiya S, Chavhan S, Korde A, Sawant KK. Solid lipid nanoparticles and nanosuspension of adefovir dipivoxil for bioavailability improvement: Formulation, characterization, pharmacokinetic and biodistribution studies. Drug Dev Ind Pharm 2013; 39(5): 733-43.
[http://dx.doi.org/10.3109/03639045.2012.694889] [PMID: 22690834]
[30]
Raval N, Maheswari R, Kalyane D, et al. Importance of physicochemical characterization of nanoparticles in pharmaceutical product development. In: Advances in Pharmaceutical Product Development and Research 2019; pp. 369-400.
[http://dx.doi.org/10.1016/B978-0-12-817909-3.00010-8]
[31]
Muthu MS, Rawat MK, Mishra A, Singh S. PLGA nanoparticle formulations of risperidone: preparation and neuropharmacological evaluation. Nanomedicine 2009; 5(3): 323-33.
[http://dx.doi.org/10.1016/j.nano.2008.12.003] [PMID: 19523427]
[32]
Gill P, Moghadam TT, Ranjbar B. Differential scanning calorimetry techniques: Applications in biology and nanoscience. J Biomol Tech 2010; 21(4): 167-93.
[PMID: 21119929]
[33]
Leyva-Porras C, Cruz-Alcantar P, Espinosa-Solis V, et al. Applications of Differential Scanning Calorimetry (DSC) and Modulated Differential Scanning Calorimetry (MDSC) in food and drug industries. Polymers 2020; 12(1): 5.
[http://dx.doi.org/10.3390/polym12010005]
[34]
Jammula S, Patra CN, Swain S, et al. Improvement in the dissolution rate and tableting properties of cefuroxime axetil by melt-granulated dispersion and surface adsorption. Acta Pharm Sin B 2013; 3(2): 113-22.
[http://dx.doi.org/10.1016/j.apsb.2013.01.001]
[35]
Fessi H, Puisieux F, Devissaguet JP, Ammoury N, Benita S. Nanocapsule formation by interfacial polymer deposition following solvent displacement. Int J Pharm 1989; 55(1): R1-4.
[http://dx.doi.org/10.1016/0378-5173(89)90281-0]
[36]
Marchais H, Benali S, Irache JM, Tharasse-Bloch C, Lafont O, Orecchioni AM. Entrapment efficiency and initial release of phenylbutazone from nanocapsules prepared from different polyesters. Drug Dev Ind Pharm 1998; 24(9): 883-8.
[http://dx.doi.org/10.3109/03639049809088536] [PMID: 9876542]
[37]
Huang W, Zhang C. Tuning the size of Poly(Lactic-co-Glycolic Acid) (PLGA) nanoparticles fabricated by nanoprecipitation. Biotechnol J 2018; 13(1): 1700203.
[http://dx.doi.org/10.1002/biot.201700203] [PMID: 28941234]
[38]
Kamaly N, Yameen B, Wu J, Farokhzad OC. Degradable controlled-release polymers and polymeric nanoparticles: Mechanisms of controlling drug release. Chem Rev 2016; 116(4): 2602-63.
[http://dx.doi.org/10.1021/acs.chemrev.5b00346] [PMID: 26854975]
[39]
Makadia HK, Siegel SJ. Poly Lactic-co-Glycolic Acid (PLGA) as biodegradable controlled drug delivery carrier. Polymers 2011; 3(3): 1377-97.
[http://dx.doi.org/10.3390/polym3031377] [PMID: 22577513]
[40]
Hines DJ, Kaplan DL. Poly(lactic-co-glycolic) acid-controlled-release systems: Experimental and modeling insights. Crit Rev Ther Drug Carrier Syst 2013; 30(3): 257-76.
[http://dx.doi.org/10.1615/CritRevTherDrugCarrierSyst.2013006475] [PMID: 23614648]
[41]
Visan AI, Popescu-Pelin G, Socol G. Degradation behavior of polymers used as coating materials for drug delivery-A basic review. Polymers 2021; 13(8): 1272.
[http://dx.doi.org/10.3390/polym13081272]
[42]
Fredenberg S, Wahlgren M, Reslow M, Axelsson A. The mechanisms of drug release in poly(lactic-co-glycolic acid)-based drug delivery systems-A review. Int J Pharm 2011; 415(1-2):34-52. Polymers (Basel) 2021; 13(8): 1272.
[PMID: 33919820]
[43]
Pourtalebi Jahromi L, Ghazali M, Ashrafi H, Azadi A. A comparison of models for the analysis of the kinetics of drug release from PLGA-based nanoparticles. Heliyon 2020; 6(2): e03451.
[http://dx.doi.org/10.1016/j.heliyon.2020.e03451] [PMID: 32140583]
[44]
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.
[PMID: 20524422]
[45]
Li ZZ, Wen LX, Shao L, Chen JF. Fabrication of porous hollow silica nanoparticles and their applications in drug release control. J Control Release 2004; 98(2): 245-54.
[http://dx.doi.org/10.1016/j.jconrel.2004.04.019] [PMID: 15262416]
[46]
Jammula S, Patra ChN, Swain S, et al. Design and characterization of cefuroxime axetil biphasic floating minitablets. Drug Deliv 2015; 22(1): 125-35.
[http://dx.doi.org/10.3109/10717544.2013.871603] [PMID: 24417642]