Functionally Tailored Electro-Sensitive Poly(Acrylamide)-g-Pectin Copolymer Hydrogel for Transdermal Drug Delivery Application: Synthesis, Characterization, In-vitro and Ex-vivo Evaluation

Author(s): Sudha B. Patil, Syed Z. Inamdar, Kakarla R. Reddy, Anjanapura V. Raghu, Krishnamachari G. Akamanchi, Arun C. Inamadar, Kusal K. Das, Raghavendra V. Kulkarni*

Journal Name: Drug Delivery Letters

Volume 10 , Issue 3 , 2020

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Abstract:

Background: To develop electro-sensitive transdermal drug delivery systems (ETDDS) using polyacrylamide-grafted-pectin (PAAm-g-PCT) copolymer hydrogel for rivastigmine delivery.

Methods: Free radical polymerization and alkaline hydrolysis technique was employed to synthesize PAAm-g-PCT copolymer hydrogel. The PAAm-g-PCT copolymeric hydrogel was used as a reservoir and cross-linked blend films of PCT and poly(vinyl alcohol) as rate-controlling membranes (RCMs) to prepare ETDDS.

Results: The pH of the hydrogel reservoir was found to be in the range of 6.81 to 6.93 and drug content was 89.05 to 96.29%. The thickness of RCMs was in the range of 51 to 99 μ and RCMs showed permeability behavior against water vapors. There was a reduction in the water vapor transmission rate as the glutaraldehyde (GA) concentration was increased. The drug permeation rate from the ETDDS was enhanced under the influence of electric stimulus against the absence of an electric stimulus. The increase in flux by 1.5 fold was recorded with applied electric stimulus. The reduction in drug permeability observed when the concentration of GA was increased. Whereas, the permeability of the drug was augmented as an electric current was changed from 2 to 8 mA. The pulsatile drug release under “on– off” cycle of electric stimulus witnessed a faster drug release under ‘on’ condition and it was slow under ‘off’ condition. The alteration in skin composition after electrical stimulation was confirmed through histopathology studies.

Conclusion: The PAAm-g-PCT copolymer hydrogel is a useful carrier for transdermal drug delivery activated by an electric signal to provide on-demand release of rivastigmine.

Keywords: Electro-sensitive, hydrogel, grafting, transdermal drug delivery, Alzheimer`s disease, rivastigmine.

[1]
Lin, C.C.; Metters, A.T. Hydrogels in controlled release formulations: network design and mathematical modeling. Adv. Drug Deliv. Rev., 2006, 58(12-13), 1379-1408.
[http://dx.doi.org/10.1016/j.addr.2006.09.004] [PMID: 17081649]
[2]
Sprincl, L.; Kopecek, J.; Vacík, J.; Lím, D. Biological tolerance of poly(N-substituted methacrylamides). J. Biomed. Mater. Res., 1971, 5(3), 197-205.
[http://dx.doi.org/10.1002/jbm.820050307] [PMID: 5560996]
[3]
Sprincl, L.; Vacík, J.; Kopecek, J. Biological tolerance of ionogenic hydrophilic gels. J. Biomed. Mater. Res., 1973, 7(1), 123-136.
[http://dx.doi.org/10.1002/jbm.820070110] [PMID: 4691155]
[4]
Laurén, P.; Somersalo, P.; Pitkänen, I.; Lou, Y-R.; Urtti, A.; Partanen, J.; Seppälä, J.; Madetoja, M.; Laaksonen, T.; Mäkitie, A.; Yliperttula, M. Nanofibrillar cellulose-alginate hydrogel coated surgical sutures as cell-carrier systems. PLoS One, 2017, 12(8), e0183487.
[http://dx.doi.org/10.1371/journal.pone.0183487] [PMID: 28829830]
[5]
Kim, S.; Feinberg, B.; Kant, R.; Chui, B.; Goldman, K.; Park, J.; Moses, W.; Blaha, C.; Iqbal, Z.; Chow, C.; Wright, N.; Fissell, W.H.; Zydney, A.; Roy, S. Diffusive silicon nanopore membranes for hemodialysis applications. PLoS One, 2016, 11(7), e0159526.
[http://dx.doi.org/10.1371/journal.pone.0159526] [PMID: 27438878]
[6]
Singh, A.; Narvi, S.S.; Dutta, P.K.; Pandey, N.D. External stimuli response on a novel chitosan hydrogel crosslinked with formaldehyde. Bull. Mater. Sci., 2006, 29, 233-238.
[http://dx.doi.org/10.1007/BF02706490]
[7]
Kishi, R.; Ichijo, H.; Hirasa, O. Thermo-responsive devices using poly(vinylmethyl ether) hydrogels. J. Intell. Mater. Syst. Struct., 1993, 4, 533-537.
[http://dx.doi.org/10.1177/1045389X9300400413]
[8]
Qiu, Y.; Park, K. Environment-sensitive hydrogels for drug delivery. Adv. Drug Deliv. Rev., 2001, 53(3), 321-339.
[http://dx.doi.org/10.1016/S0169-409X(01)00203-4] [PMID: 11744175]
[9]
Suzuki, A.; Tanaka, T. Phase transition in polymer gels induced by visible light. Nature, 1990, 346, 345-347.
[http://dx.doi.org/10.1038/346345a0]
[10]
Priano, L.; Gasco, M.R.; Mauro, A. Transdermal treatment options for neurological disorders: impact on the elderly. Drugs Aging, 2006, 23(5), 357-375.
[http://dx.doi.org/10.2165/00002512-200623050-00001] [PMID: 16823990]
[11]
Sawada, H.; Kawakami, J.; Kawamura, N.; Yamauchi, H.; Takayama, S. Influence of combinations of enhancers on skin permeation of meloxicam. Drug Deliv. Syst., 2006, 21, 537-544.
[http://dx.doi.org/10.2745/dds.21.537]
[12]
Mitragotri, S.; Blankschtein, D.; Langer, R. Ultrasound-mediated transdermal protein delivery. Science, 1995, 269(5225), 850-853.
[http://dx.doi.org/10.1126/science.7638603] [PMID: 7638603]
[13]
Chan, A.L.; Chien, Y.W.; Jin, Lin S. Transdermal delivery of treatment for Alzheimer’s disease: development, clinical performance and future prospects. Drugs Aging, 2008, 25(9), 761-775.
[http://dx.doi.org/10.2165/00002512-200825090-00003] [PMID: 18729547]
[14]
Assal, F.; Cummings, J.L. Neuropsychiatric symptoms in the dementias. Curr. Opin. Neurol., 2002, 15(4), 445-450.
[http://dx.doi.org/10.1097/00019052-200208000-00007] [PMID: 12151841]
[15]
Lee, L.; Hossain, M.; Wang, Y.; Sedek, G. Absorption of rivastigmine from different regions of the gastrointestinal tract in humans. J. Clin. Pharmacol., 2004, 44(6), 599-604.
[http://dx.doi.org/10.1177/0091270004265645] [PMID: 15145967]
[16]
Kulkarni, R.V.; Sa, B. Enteric delivery of ketoprofen through functionally modified poly(acrylamide-grafted-xanthan)-based pH-sensitive hydrogel beads: preparation, in vitro and in vivo evaluation. J. Drug Target., 2008, 16(2), 167-177.
[http://dx.doi.org/10.1080/10611860701792399] [PMID: 18274937]
[17]
Alange, V.V.; Birajdar, R.P.; Kulkarni, R.V. Novel spray dried pH sensitive polyacrylamide-grafted-carboxymethylcellulose sodium copolymer microspheres for colon targeted delivery of an anti cancer drug. J. Biomater. Sci. Polym. Ed., 2017, 28(2), 139-161.
[http://dx.doi.org/10.1080/09205063.2016.1257083] [PMID: 27808009]
[18]
Birajdar, R.P.; Patil, S.B.; Alange, V.V.; Kulkarni, R.V. Electro responsive polyacrylamide-grafted-gum ghatti copolymer for transdermal drug delivery application. J. Macromol. Sci. Part A Pure Appl. Chem., 2019, 56, 306-315.
[http://dx.doi.org/10.1080/10601325.2019.1574539]
[19]
Mutalik, S.; Udupa, N. Formulation development, in vitro and in vivo evaluation of membrane controlled transdermal systems of glibenclamide. J. Pharm. Pharm. Sci., 2005, 8(1), 26-38.
[PMID: 15946595]
[20]
Pillai, O.; Panchagnula, R. Transdermal delivery of insulin from poloxamer gel: ex vivo and in vivo skin permeation studies in rat using iontophoresis and chemical enhancers. J. Control. Release, 2003, 89(1), 127-140.
[http://dx.doi.org/10.1016/S0168-3659(03)00094-4] [PMID: 12695068]
[21]
Birajdar, R.P.; Patil, S.S.; Alange, V.V.; Kulkarni, R.V. Electrically triggered transdermal drug delivery utilizing poly(Acrylamide)- graft-guar gum: Synthesis, characterization and formulation development. Curr. Appl. Polym. Sci., 2019, 3(1), 64-74.
[http://dx.doi.org/10.2174/2452271602666181031093243]
[22]
Alange, V.V.; Birajdar, R.P.; Kulkarni, R.V. Functionally modified polyacrylamide-graft-gum karaya pH-sensitive spray dried microspheres for colon targeting of an anti cancer drug. Int. J. Biol. Macromol., 2017, 102, 829-839.
[http://dx.doi.org/10.1016/j.ijbiomac.2017.04.023] [PMID: 28392387]
[23]
Patil, S.B.; Inamdar, S.Z.; Reddy, K.R.; Raghu, A.V.; Soni, S.K.; Kulkarni, R.V. Novel biocompatible poly(acrylamide)-grafted dextran hydrogels: Synthesis, characterization and biomedical applications. J. Microbiol. Methods, 2019, 159, 200-210.
[http://dx.doi.org/10.1016/j.mimet.2019.03.009] [PMID: 30877016]
[24]
Kulkarni, R.V.; Setty, C.M.; Sa, B. Polyacrylamide-g-alginate based electrically responsive hydrogel for drug delivery application: Synthesis, characterization, and formulation development. J. Appl. Polym. Sci., 2010, 115, 1180-1188.
[http://dx.doi.org/10.1002/app.31203]


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Article Details

VOLUME: 10
ISSUE: 3
Year: 2020
Published on: 10 September, 2020
Page: [185 - 196]
Pages: 12
DOI: 10.2174/2210303110666200206114632
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