Enhancement of Losartan Transdermal Transport Through Incorporation into Chitosan Nanoparticles

Nuri Ari Efiana, Akhmad Kharis Nugroho, Ronny Martien

Abstrak


Losartan, an antihypertensive agent, has low oral bioavailability. Therefore, developing a design for transdermal delivery of losartan is interesting. This study aims to enhance losartan in vitro transport by incorporating it into chitosan nanoparticles. Transdermal transport studies were conducted using two experimental groups: the pretreatment group using oleic acid and propylene glycol, and the group without pretreatment. The results showed that losartan incorporated into chitosan nanoparticles resulted in a significantly higher amount of drug being transported than the losartan solution (control) in both experimental groups. In the experiment without pretreatment, the amount of losartan from the control could not be detected in the receptor compartment until 28 hours. In contrast, losartan was detected at 16 hours of transport from chitosan nanoparticles. In pretreatment, chitosan nanoparticles exhibited 6.6fold higher losartan transport than the control. In addition, losartan chitosan nanoparticles showed significant increases in steady-state flux and transport efficiency by 3.3 and 6.6 times higher than the control, respectively. It can be concluded that the incorporation of losartan into chitosan nanoparticles can increase its transdermal transport.


Kata Kunci


chitosan; losartan; nanoparticles; transdermal

Teks Lengkap:

PDF (English)

Referensi


Regenthal R, Voskanian M, Baumann F, Teichert J, Brätter C, Aigner A, Abraham G. Pharmacokinetic evaluation of a transdermal anastrozole-in-adhesive formulation. Drug Des Devel Ther 2018; 12: 3653–64.

Trivedi R, Umekar M, Kotagale N, Bonde S, Taksande J. Design, evaluation and in vivo pharmacokinetic study of a cationic flexible liposomes for enhanced transdermal delivery of pramipexole. J Drug Deliv Sci Technol 2021; 61: 102313.

Morsi NM, Aboelwafa AA, Dawoud MHS. Improved bioavailability of timolol maleate via transdermal transfersomal gel: Statistical optimization, characterization, and pharmacokinetic assessment. J Adv Res 2016; 7: 691–701.

Burki FA, Shah KU, Razaque G, Shah SU, Nawaz A, Saeed MD, Rehman MU, Bibi H, Alfatama M, Elsayed TM. Optimization of Chitosan-Decorated Solid Lipid Nanoparticles for Improved Flurbiprofen Transdermal Delivery. ACS Omega 2023; 8: 19302–10.

Baek J-S, Cho C-W. Transdermal delivery of tadalafil using a novel formulation. Drug Deliv 2016; 23: 1571–7.

Teaima M, Abdelmonem R, Adel YA, El-Nabarawi MA, El-Nawawy TM. Transdermal Delivery of Telmisartan: Formulation, in vitro, ex vivo, Iontophoretic Permeation Enhancement and Comparative Pharmacokinetic Study in Rats. Drug Des Devel Ther 2021; 15: 4603–14.

Pandey SS, Patel MA, Desai DT, Patel HP, Gupta AR, Joshi SV, Shah DO, Maulvi FA. Bioavailability enhancement of repaglinide from transdermally applied nanostructured lipid carrier gel: Optimization, in vitro and in vivo studies. J Drug Deliv Sci Technol 2020; 57: 101731.

El-Tokhy FS, Abdel-Mottaleb MMA, Abdel Mageed SS, Mahmoud AMA, El-Ghany EA, Geneidi AS. Boosting the In Vivo Transdermal Bioavailability of Asenapine Maleate Using Novel Lavender Oil-Based Lipid Nanocapsules for Management of Schizophrenia. Pharmaceutics 2023; 15: 490.

Naguib MJ, Elsayed I, Teaima MH. Simultaneous Optimization of Oral and Transdermal Nanovesicles for Bioavailability Enhancement of Ivabradine Hydrochloride. Int J Nanomedicine 2021; 16: 2917–31.

Mo L, Lu G, Ou X, Ouyang D. Formulation and development of novel control release transdermal patches of carvedilol to improve bioavailability for the treatment of heart failure. Saudi J Biol Sci 2022; 29: 266–72.

Mazhar D, Haq NU, Zeeshan M, Ain QU, Ali H, Khan S, Khan SA. Preparation, characterization, and pharmacokinetic assessment of metformin HCl loaded transfersomes co-equipped with permeation enhancer to improve drug bioavailability via transdermal route. J Drug Deliv Sci Technol 2023; 84: 104448.

Alsaqr A, Rasoully M, Musteata FM. Investigating Transdermal Delivery of Vitamin D3. AAPS PharmSciTech 2015; 16: 963–72.

Abdo JM, Sopko NA, Milner SM. The applied anatomy of human skin: A model for regeneration. Wound Med 2020; 28: 100179.

Gorzelanny C, Mess C, Schneider SW, Huck V, Brandner JM. Skin Barriers in Dermal Drug Delivery: Which Barriers Have to Be Overcome and How Can We Measure Them? Pharmaceutics 2020; 12: 684.

Sica DA, Gehr TWB, Ghosh S. Clinical Pharmacokinetics of Losartan. Clin Pharmacokinet 2005; 44: 797–814.

Lio DCS, Liu C, Oo MMS, Wiraja C, Teo MHY, Zheng M, Chew SWT, Wang X, Xu C. Transdermal delivery of small interfering RNAs with topically applied mesoporous silica nanoparticles for facile skin cancer treatment. Nanoscale 2019; 11: 17041–51.

Nair RS, Morris A, Billa N, Leong C-O. An Evaluation of Curcumin-Encapsulated Chitosan Nanoparticles for Transdermal Delivery. AAPS PharmSciTech 2019; 20: 69.

Jeong WY, Kim S, Lee SY, Lee H, Han DW, Yang SY, Kim KS. Transdermal delivery of Minoxidil using HA-PLGA nanoparticles for the treatment in alopecia. Biomater Res 2019; 23: 16.

Zou JJ, Le JQ, Zhang BC, Yang MY, Jiang JL, Lin JF, et al. Accelerating transdermal delivery of insulin by ginsenoside nanoparticles with unique permeability. Int J Pharm 2021; 605: 120784.

Xiang H, Xu S, Li J, Pan S, Miao X. Particle Size Effect of Curcumin Nanocrystals on Transdermal and Transfollicular Penetration by Hyaluronic Acid-Dissolving Microneedle Delivery. Pharmaceuticals 2022; 15: 206.

Dilawar N, Ur-Rehman T, Shah KU, Fatima H, Alhodaib A. Development and Evaluation of PLGA Nanoparticle-Loaded Organogel for the Transdermal Delivery of Risperidone. Gels 2022; 8: 709.

Lan X, She J, Lin D, Xu Y, Li X, Yang W, Lui VWY, Jin L, Xie X, Su Y. Microneedle-Mediated Delivery of Lipid-Coated Cisplatin Nanoparticles for Efficient and Safe Cancer Therapy. ACS Appl Mater Interfaces 2018; 10: 33060–9.

Uchida N, Yanagi M, Hamada H. Transdermal Delivery of Anionic Phospholipid Nanoparticles Containing Fullerene. Nat Prod Commun 2022; 17: 1934578X221078444.

Uchida N, Yanagi M, shimoda K, Hamada H. Transdermal Delivery of Small-Sized Resveratrol Nanoparticles to Epidermis Using Anionic Phospholipids. Nat Prod Commun 2020; 15: 1934578X20951443.

Zhang P, Zhang Y, Liu C-G. Polymeric nanoparticles based on carboxymethyl chitosan in combination with painless microneedle therapy systems for enhancing transdermal insulin delivery. RSC Adv 2020; 10: 24319–29.

Talib S, Ahmed N, Khan D, Khan GM, Rehman A ur. Chitosan-chondroitin based artemether loaded nanoparticles for transdermal drug delivery system. J Drug Deliv Sci Technol 2021; 61: 102281.

Zhang K, Zhuang Y, Zhang W, Guo Y, Liu X. Functionalized MoS2-nanoparticles for transdermal drug delivery of atenolol. Drug Deliv 2020; 27: 909–16.

Zeng L, Tao C, Liu Z, Zhang J, Zhang M, Zhang J, Fang S, Ma X, Song H, Zhou X. Preparation and Evaluation of Cubic Nanoparticles for Improved Transdermal Delivery of Propranolol Hydrochloride. AAPS PharmSciTech 2020; 21: 266.

Shahraeini SS, Akbari J, Saeedi M, Morteza-Semnani K, Abootorabi S, Dehghanpoor M, Rostamkalaei SS, Nokhodchi A. Atorvastatin Solid Lipid Nanoparticles as a Promising Approach for Dermal Delivery and an Anti-inflammatory Agent. AAPS PharmSciTech 2020; 21: 263.

Zaid Alkilani A, Nimrawi S, Al-Nemrawi NK, Nasereddin J. Microneedle-assisted transdermal delivery of amlodipine besylate loaded nanoparticles. Drug Dev Ind Pharm 2022; 48: 322–32.

Gu Y, Yang M, Tang X, Wang T, Yang D, Zhai G, Liu J. Lipid nanoparticles loading triptolide for transdermal delivery: mechanisms of penetration enhancement and transport properties. J Nanobiotechnology 2018; 16: 68.

Ali HS, Namazi N, Elbadawy HM, El-Sayed AA, Ahmed SA, Bafail R, Almikhlafi MA, Alahmadi YM. Repaglinide–Solid Lipid Nanoparticles in Chitosan Patches for Transdermal Application: Box–Behnken Design, Characterization, and In Vivo Evaluation. Int J Nanomedicine 2024; 19: 209–30.

Efiana NA, Nugroho AK, Martien R. Formulation of Losartan Nanoparticles with Chitosan as a Carrier. J ILMU KEFARMASIAN Indones 2013; 11: 7–12.

Binarjo A, Nugroho A. Improvement of Losartan Transdermal Permeation using Oleic Acid Pretreatment: in Vitro Observation and in Vivo Prediction. Pharm Sci Res 2019 Apr 30; 6. doi: 10.7454/psr.v6i1.4120

Binarjo A, Nugroho AK. Studi Penetapan Kadar Losartan dengan Metode Spektrofotometri dan High Performance Liquid Chromatography (HPLC) serta Aplikasinya pada Transpor Transdermal in Vitro. Pharmaciana 2013; 3: 31–48.

Martin AN, Bustamante P. Physical Pharmacy: Physical Chemical Principles in the Pharmaceutical Sciences. Philadelphia: Lea & Febiger, 1993. .

Wilson A, Ekanem EE, Mattia D, Edler KJ, Scott JL. Keratin–Chitosan Microcapsules via Membrane Emulsification and Interfacial Complexation. ACS Sustain Chem Eng 2021; 9: 16617–26.

Barbosa AI, Costa Lima SA, Reis S. Development of methotrexate loaded fucoidan/chitosan nanoparticles with anti-inflammatory potential and enhanced skin permeation. Int J Biol Macromol 2019; 124: 1115–22.

Khan TA, Azad AK, Fuloria S, Nawaz A, Subramaniyan V, Akhlaq M, Safdar M, Sathasivam KV, Sekar M, Porwal O, Meenakshi DU, Malviya R, Miret MM, Mendiratta A, Fuloria NK. Chitosan-Coated 5-Fluorouracil Incorporated Emulsions as Transdermal Drug Delivery Matrices. Polymers 2021; 13: 3345.

Lee E-H, Lim S-J, Lee M-K. Chitosan-coated liposomes to stabilize and enhance transdermal delivery of indocyanine green for photodynamic therapy of melanoma. Carbohydr Polym 2019; 224: 115143.

Zhou X, You G, Liu D, Yao K. In Vitro Investigation on The Interactions of Oligo-Chitosan with Keratin. Acta Polym Sin 2009; 009: 781–5.

Jafri I, Shoaib MH, Yousuf RI, Ali FR. Effect of permeation enhancers on in vitro release and transdermal delivery of lamotrigine from Eudragit®RS100 polymer matrix-type drug in adhesive patches. Prog Biomater 2019; 8: 91–100.

Bednarczyk P, Nowak A, Duchnik W, Kucharski Ł, Ossowicz-Rupniewska P. Enhancing Transdermal Delivery: Investigating the Impact of Permeation Promoters on Ibuprofen Release and Penetration from Medical Patches-In Vitro Research. Int J Mol Sci 2023; 24: 15632.

Verma S, Utreja P. Oleic Acid Vesicles as a new Approach for Transdermal Delivery of Econazole Nitrate: Development, Characterization, and In-vivo Evaluation in Wistar rats. Recent Patents Anti-Infect Drug Disc 2020; 16: 30–49.

Lei Y, Yang G, Du F, Yi J, Quan L, Liu H, Zhou X, Gong W, Han J, Wang Y, Gao C. Formulation and Evaluation of a Drug-in-Adhesive Patch for Transdermal Delivery of Colchicine. Pharmaceutics 2022; 14: 2245.

Lai W-F, Tang R, Wong W-T. Ionically Crosslinked Complex Gels Loaded with Oleic Acid-Containing Vesicles for Transdermal Drug Delivery. Pharmaceutics 2020; 12: 725.

Kim KT, Kim JS, Kim M-H, Park J-H, Lee J-Y, Lee W, Min KK, Song MG, Choi C-Y, Kim W-S, Oh HK, Kim D-D. Effect of Enhancers on in vitro and in vivo Skin Permeation and Deposition of S-Methyl-l-Methionine. Biomol Ther 2017; 25: 434–40.

Atef E, Altuwaijri N. Using Raman Spectroscopy in Studying the Effect of Propylene Glycol, Oleic Acid, and Their Combination on the Rat Skin. AAPS PharmSciTech 2018; 19: 114–22.

Virani A, Puri V, Mohd H, Michniak-Kohn B. Effect of Penetration Enhancers on Transdermal Delivery of Oxcarbazepine, an Antiepileptic Drug Using Microemulsions. Pharmaceutics 2023; 15: 183.

Haq A, Michniak-Kohn B. Effects of solvents and penetration enhancers on transdermal delivery of thymoquinone: permeability and skin deposition study. Drug Deliv 2018; 25: 1943–9.

Trommer H, Neubert RHH. Overcoming the stratum corneum: the modulation of skin penetration. A review. Skin Pharmacol Physiol 2006; 19: 106–21.

Hashmat D, Shoaib MH, Ali FR, Siddiqui F. Lornoxicam controlled release transdermal gel patch: Design, characterization and optimization using co-solvents as penetration enhancers. PloS One 2020; 15: e0228908.

Hendriati L, Nugroho AK. The influence of oleic acid-propylene glycol mixture and iontophoresis to propranolol transdermal transport. Indones J Pharm 2009; 20: 217–23.

Nagai N, Ogata F, Ishii M, Fukuoka Y, Otake H, Nakazawa Y, Kawasaki N. Involvement of Endocytosis in the Transdermal Penetration Mechanism of Ketoprofen Nanoparticles. Int J Mol Sci 2018; 19: 2138.

Wu X, Landfester K, Musyanovych A, Guy RH. Disposition of charged nanoparticles after their topical application to the skin. Skin Pharmacol Physiol 2010; 23: 117–23.




DOI: https://doi.org/10.24198/ijpst.v12i2.49978

Refbacks

  • Saat ini tidak ada refbacks.


 Switch to English

Back to Top

View My Stats

Penerbit Universitas Padjadjaran

Jurnal ini terindeks di :

      

Creative Commons Attribution :

Creative Commons License
Indonesian Journal of Pharmaceutical Science and Technology by Universitas Padjadjaran is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

Based on a work at http://jurnal.unpad.ac.id/ijpst/