Login Register Cart 0
Generic placeholder image

Current Drug Delivery

Editor-in-Chief

ISSN (Print): 1567-2018
ISSN (Online): 1875-5704

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Transdermal Drug Delivery System of Linagliptin Sustained-release Microparticle Gels: In vitro Characterization and In vivo Evaluation

Author(s): Jiayan Liu, Song Guo, Shuai Hong, Jingshu Piao* and Mingguan Piao*

Volume 21, Issue 11, 2024

Published on: 11 January, 2024

Page: [1537 - 1547] Pages: 11

DOI: 10.2174/0115672018279370240103062944

Price: $65

Abstract

Background: Linagliptin (LNG) exhibits poor bioavailability and numerous side effects, significantly limiting its use. Transdermal drug delivery systems (TDDS) offer a potential solution to overcome the first-pass effect and gastrointestinal reactions associated with oral formulations.

Objective: The aim of this study was to develop LNG microparticle gels to enhance drug bioavailability and mitigate side effects.

Methods: Linagliptin hyaluronic acid (LNG-HA) microparticles were prepared by spray drying method and their formulation was optimized via a one-factor method. The solubility and release were investigated using the slurry method. LNG-HA microparticle gels were prepared and optimised using in vitrotransdermal permeation assay. The hypoglycaemic effect of the LNG-HA microparticle gel was examined on diabetic mice.

Results: The results indicated that the LNG-HA microparticle encapsulation rate was 84.46%. Carbomer was selected as the gel matrix for the microparticle gels. Compared to the oral API, the microparticle gel formulation demonstrated a distinct biphasic release pattern. In the first 30 minutes, only 43.56% of the drug was released, followed by a gradual release. This indicates that the formulation achieved a slow-release effect from a dual reservoir system. Furthermore, pharmacodynamic studies revealed a sustained hypoglycemic effect lasting for 48 hours with the LNG microparticle gel formulation.

Conclusion: These findings signify that the LNG microparticle gel holds significant clinical value for providing sustained release and justifies its practical application.

« Previous Next »
[1]
D, P.; Yanmanagandla, D.; Sripada, R.D. Formulation and evaluation of linagliptin mucoadhesive microspheres. Int. Res. J. Pharma., 2018, 9(5), 11-17.
[http://dx.doi.org/10.7897/2230-8407.09567]
[2]
Graefe-Mody, U.; Retlich, S.; Friedrich, C. Clinical pharmacokinetics and pharmacodynamics of linagliptin. Clin. Pharmacokinet., 2012, 51(7), 411-427.
[http://dx.doi.org/10.2165/11630900-000000000-00000] [PMID: 22568694]
[3]
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.
[http://dx.doi.org/10.1007/s13346-020-00839-9] [PMID: 32804301]
[4]
Saeedi, P.; Petersohn, I.; Salpea, P.; Malanda, B.; Karuranga, S.; Unwin, N.; Colagiuri, S.; Guariguata, L.; Motala, A.A.; Ogurtsova, K.; Shaw, J.E.; Bright, D.; Williams, R. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9th edition. Diabetes Res. Clin. Pract., 2019, 157, 107843.
[http://dx.doi.org/10.1016/j.diabres.2019.107843] [PMID: 31518657]
[5]
Despotopoulou, D.; Lagopati, N.; Pispas, S.; Gazouli, M.; Demetzos, C.; Pippa, N. The technology of transdermal delivery nanosystems: From design and development to preclinical studies. Int. J. Pharm., 2022, 611, 121290.
[http://dx.doi.org/10.1016/j.ijpharm.2021.121290] [PMID: 34788674]
[6]
Carter, P.; Narasimhan, B.; Wang, Q. Biocompatible nanoparticles and vesicular systems in transdermal drug delivery for various skin diseases. Int. J. Pharm., 2019, 555, 49-62.
[http://dx.doi.org/10.1016/j.ijpharm.2018.11.032] [PMID: 30448309]
[7]
Escobar-Chávez, J.J.; Rodríguez-Cruz, I.M.; Domínguez-Delgado, C.L.; Díaz-Torres, R.; Aléncaster, N.C. Nanocarrier systems for transdermal drug delivery. In: Recent Advances in Novel Drug Carrier Systems; IntechOpen: London, 2012.
[8]
Zhao, W.; Ma, L.; Guo, S.; Liu, J.Y.; Piao, J.; Piao, M. Transdermal drug delivery system of domperidone sustained-release coated microsphere gels: In vitro characterization and In vivo evaluation. J. Drug Deliv. Sci. Technol., 2022, 78, 103939.
[http://dx.doi.org/10.1016/j.jddst.2022.103939]
[9]
Lane, M.E. Skin penetration enhancers. Int. J. Pharm., 2013, 447(1-2), 12-21.
[http://dx.doi.org/10.1016/j.ijpharm.2013.02.040] [PMID: 23462366]
[10]
Schoellhammer, C.M.; Blankschtein, D.; Langer, R. Skin permeabilization for transdermal drug delivery: Recent advances and future prospects. Expert Opin. Drug Deliv., 2014, 11(3), 393-407.
[http://dx.doi.org/10.1517/17425247.2014.875528] [PMID: 24392787]
[11]
Pegoraro, C.; MacNeil, S.; Battaglia, G. Transdermal drug delivery: From micro to nano. Nanoscale, 2012, 4(6), 1881-1894.
[http://dx.doi.org/10.1039/c2nr11606e] [PMID: 22334401]
[12]
Hadgraft, J.; Lane, M.E. Skin permeation: The years of enlightenment. Int. J. Pharm., 2005, 305(1-2), 2-12.
[http://dx.doi.org/10.1016/j.ijpharm.2005.07.014] [PMID: 16246513]
[13]
Santos, L.F.; Correia, I.J.; Silva, A.S.; Mano, J.F. Biomaterials for drug delivery patches. Eur. J. Pharm. Sci., 2018, 118, 49-66.
[http://dx.doi.org/10.1016/j.ejps.2018.03.020] [PMID: 29572160]
[14]
Hoare, T.R.; Kohane, D.S. Hydrogels in drug delivery: Progress and challenges. Polymer, 2008, 49(8), 1993-2007.
[http://dx.doi.org/10.1016/j.polymer.2008.01.027]
[15]
Shah, D.K.; Khandavilli, S.; Panchagnula, R. Alteration of skin hydration and its barrier function by vehicle and permeation enhancers: A study using TGA, FTIR, TEWL and drug permeation as markers. Methods Find. Exp. Clin. Pharmacol., 2008, 30(7), 499-512.
[http://dx.doi.org/10.1358/mf.2008.30.7.1159653] [PMID: 18985178]
[16]
Panchagnula, R.; Salve, P.S.; Thomas, N.S.; Jain, A.K.; Ramarao, P. Transdermal delivery of naloxone: Effect of water, propylene glycol, ethanol and their binary combinations on permeation through rat skin. Int. J. Pharm., 2001, 219(1-2), 95-105.
[http://dx.doi.org/10.1016/S0378-5173(01)00634-2] [PMID: 11337170]
[17]
Gu, B.; Sun, X.; Papadimitrakopoulos, F.; Burgess, D.J. Seeing is believing, PLGA microsphere degradation revealed in PLGA microsphere/PVA hydrogel composites. J. Control. Release, 2016, 228, 170-178.
[http://dx.doi.org/10.1016/j.jconrel.2016.03.011] [PMID: 26965956]
[18]
Wang, J.; Wang, B.M.; Schwendeman, S.P. Characterization of the initial burst release of a model peptide from poly(d,l-lactide-co-glycolide) microspheres. J. Control. Release, 2002, 82(2-3), 289-307.
[http://dx.doi.org/10.1016/S0168-3659(02)00137-2] [PMID: 12175744]
[19]
Kang, J.; Schwendeman, S.P. Pore closing and opening in biodegradable polymers and their effect on the controlled release of proteins. Mol. Pharm., 2007, 4(1), 104-118.
[http://dx.doi.org/10.1021/mp060041n] [PMID: 17274668]
[20]
Huh, Y.; Cho, H.J.; Yoon, I.S.; Choi, M.K.; Kim, J.S.; Oh, E.; Chung, S.J.; Shim, C.K.; Kim, D.D. Preparation and evaluation of spray-dried hyaluronic acid microspheres for intranasal delivery of fexofenadine hydrochloride. Eur. J. Pharm. Sci., 2010, 40(1), 9-15.
[http://dx.doi.org/10.1016/j.ejps.2010.02.002] [PMID: 20149868]
[21]
Brown, M.B.; Jones, S.A. Hyaluronic acid: A unique topical vehicle for the localized delivery of drugs to the skin. J. Eur. Acad. Dermatol. Venereol., 2005, 19(3), 308-318.
[http://dx.doi.org/10.1111/j.1468-3083.2004.01180.x] [PMID: 15857456]
[22]
Zhu, J.; Tang, X.; Jia, Y.; Ho, C.T.; Huang, Q. Applications and delivery mechanisms of hyaluronic acid used for topical/transdermal delivery - A review. Int. J. Pharm., 2020, 578, 119127.
[http://dx.doi.org/10.1016/j.ijpharm.2020.119127] [PMID: 32036009]
[23]
Woo, J.S.; Piao, M.G.; Li, D.X.; Ryu, D.S.; Choi, J.Y.; Kim, J.A.; Kim, J.H.; Jin, S.G.; Kim, D.D.; Lyoo, W.S. Development of cyclosporin A-loaded hyaluronic microsphere with enhanced oral bioavailability. Int. J. Pharm., 2007, 345, 134-141.
[24]
Wu, J. Control of silk microsphere formation using polyethylene glycol (PEG). Acta Biomater., 2016, 39, 156-168.
[25]
Liu, Z.; Bu, R.; Zhao, L.; Liu, L.; Dong, N.; Zhang, Y.; Yin, T.; He, H.; Gou, J.; Tang, X. Hydrogel-containing PLGA microspheres of palonosetron hydrochloride for achieving dual-depot sustained release. J. Drug Deliv. Sci. Technol., 2021, 65, 102775.
[http://dx.doi.org/10.1016/j.jddst.2021.102775]
[26]
Thombre, A.; Tse, S.; Yeoh, T.; Chen, R.; North, R.; Brown, M. Ex vivo (human skin) and in vivo (minipig) permeation of propylene glycol applied as topical crisaborole ointment, 2%. Int. J. Pharm., 2020, 576, 118847.
[http://dx.doi.org/10.1016/j.ijpharm.2019.118847] [PMID: 31759994]
[27]
Chantasart, D.; Li, S.K. Structure enhancement relationship of chemical penetration enhancers in drug transport across the stratum corneum. Pharmaceutics, 2012, 4(1), 71-92.
[http://dx.doi.org/10.3390/pharmaceutics4010071] [PMID: 24300181]
[28]
Williams, A.C.; Barry, B.W. Penetration enhancers. Adv. Drug Deliv. Rev., 2004, 56(5), 603-618.
[http://dx.doi.org/10.1016/j.addr.2003.10.025] [PMID: 15019749]
[29]
Venuganti, V.V.K.; Perumal, O.P. Poly(amidoamine) dendrimers as skin penetration enhancers: Influence of charge, generation, and concentration. J. Pharm. Sci., 2009, 98(7), 2345-2356.
[http://dx.doi.org/10.1002/jps.21603]

Rights & Permissions Print Cite
© 2025 Bentham Science Publishers | Privacy Policy