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Planta Med 2012; 78(4): 354-361
DOI: 10.1055/s-0031-1280431
Pharmacokinetic Investigations
Original Papers
© Georg Thieme Verlag KG Stuttgart · New York

Investigating the Effect of Aloe vera Gel on the Buccal Permeability of Didanosine

Elizabeth Ojewole1 , Irene Mackraj2 , Kamil Akhundov3 , Josias Hamman4 , Alvaro Viljoen4 , Eugene Olivier4 , James Wesley-Smith5 , Thirumala Govender1
  • 1School of Pharmacy and Pharmacology, University of KwaZulu-Natal, Durban, South Africa
  • 2School of Medical Sciences, University of KwaZulu-Natal, Durban, South Africa
  • 3Plastic Surgery Department, Centre Hospitalier Universitaire Vaudois CHUV, Lausanne, Switzerland
  • 4Department of Pharmaceutical Sciences, Tshwane University of Technology, Pretoria, South Africa
  • 5Electron Microscope Unit, University of KwaZulu-Natal, Durban, South Africa
Further Information

Publication History

received Sept. 6, 2011 revised Nov. 16, 2011

accepted Nov. 18, 2011

Publication Date:
12 December 2011 (online)

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Abstract

The buccal mucosal route offers several advantages but the delivery of certain drugs can be limited by low membrane permeability. This study investigated the buccal permeability properties of didanosine (ddI) and assessed the potential of Aloe vera gel (AVgel) as a novel buccal permeation enhancer. Permeation studies were performed using Franz diffusion cells, and the drug was quantified by UV spectroscopy. Histomorphological evaluations were undertaken using light and transmission electron microscopy. The permeability of ddI was concentration-dependent, and it did not have any adverse effects on the buccal mucosae. A linear relationship (R2 = 0.9557) between the concentrations and flux indicated passive diffusion as the mechanism of drug transport. AVgel at concentrations of 0.25 to 2 %w/v enhanced ddI permeability with enhancement ratios from 5.09 (0.25 %w/v) to 11.78 (2 %w/v) but decreased permeability at 4 and 6 %w/v. Ultrastructural analysis of the buccal mucosae treated with phosphate buffer saline pH 7.4 (PBS), ddI/PBS, and ddI/PBS/AVgel 0.5 %w/v showed cells with normal plasmalemma, well-developed cristae, and nuclei with regular nuclear envelopes. However, cells from 1, 2, and 6 %w/v AVgel-treated mucosae showed irregular nuclear outlines, increased intercellular spacing, and plasmalemma crenulations. This study demonstrates the potential of AVgel as a buccal permeation enhancer for ddI to improve anti-HIV and AIDS therapy.

Key words

buccal - didanosine - permeation enhancer - histomorphology - Aloe vera (L.) Burm. F. - Aloe barbadensis Miller - Asphodelaceae

Supporting Information

References

  • 1 Rathbun R C, Lockhart S M, Stephens J R. Current HIV treatment guidelines – an overview.  Curr Pharm Des. 2006;  12 1045-1063
    Search in Google Scholar
  • 2 Heyer A, Ogunbanjo G A. Adherence to HIV antiretroviral therapy Part II: which interventions are effective in improving adherence?.  SA Fam Pract. 2006;  48 6-10
    Search in Google Scholar
  • 3 Xiang J, Fang X, Li X. Transbuccal delivery of 2′,3′-dideoxycytidine: in vitro permeation study and histological investigation.  Int J Pharm. 2002;  231 57-66
    Search in Google Scholar
  • 4 Li X, Chan W K. Transport, metabolism and elimination mechanisms of anti-HIV agents.  Adv Drug Deliv Rev. 1999;  39 81-103
    Search in Google Scholar
  • 5 Pather S I, Rathbone M J, Senel S. Current status and the future of buccal drug delivery systems.  Expert Opin Drug Deliv. 2008;  5 531-542
    Search in Google Scholar
  • 6 Rossi S, Sandri G, Caramella C M. Buccal drug delivery: A challenge already won?.  Drug Discov Today Technol. 2005;  2 59-65
    Search in Google Scholar
  • 7 Salamat-Miller N, Chittchang M, Johnston T P. The use of mucoadhesive polymers in buccal drug delivery.  Adv Drug Deliv Rev. 2005;  57 1666-1691
    Search in Google Scholar
  • 8 Narishetty S T K, Panchagnula R. Effect of L-menthol and 1,8-cineole on phase behaviour and molecular organization of SC lipids and skin permeation of zidovudine.  J Control Release. 2005;  102 59-70
    Search in Google Scholar
  • 9 Mukherji E, Millenbaugh N J, Au J L. Percutaneous absorption of 2′,3′-dideoxyinosine in rats.  Pharm Res. 1994;  11 809-815
    Search in Google Scholar
  • 10 Giannola L I, De Caro V, Giandalia G, Siragusa M G, Tripodo C, Florena A M, Campisi G. Release of naltrexone on buccal mucosa: permeation studies, histological aspects and matrix system design.  Eur J Pharm Biopharm. 2007;  67 425-433
    Search in Google Scholar
  • 11 Senel S, Hincal A A. Drug permeation enhancement via buccal route: possibilities and limitations.  J Control Release. 2001;  72 133-144
    Search in Google Scholar
  • 12 Femenia A, Sánchez E S, Simal S, Rosselló C. Compositional features of polysaccharides from Aloe vera (Aloe barbadensis Miller) plant tissues.  Carbohydr Polym. 1999;  39 109-117
    Search in Google Scholar
  • 13 Chen W, Lu Z, Viljoen A, Hamman J. Intestinal drug transport enhancement by Aloe vera.  Planta Med. 2009;  75 587-595
    Search in Google Scholar
  • 14 Reynolds T, Dweck A C. Aloe vera leaf gel: a review update.  J Ethnopharmacol. 1999;  68 3-37
    Search in Google Scholar
  • 15 Boudreau M D, Beland F A. An evaluation of the biological and toxicological properties of Aloe barbadensis (Miller), Aloe vera.  J Environ Sci Health C. 2006;  24 103-154
    Search in Google Scholar
  • 16 Pugh N, Ross S A, ElSohly M A, Pasco D S. Characterization of aloeride, a new high-molecular-weight polysaccharide from Aloe vera with potent immunostimulatory activity.  J Agric Food Chem. 2001;  49 1030-1034
    Search in Google Scholar
  • 17 Cole L, Heard C. Skin permeation enhancement potential of Aloe vera and a proposed mechanism of action based upon size exclusion and pull effect.  Int J Pharm. 2007;  333 10-16
    Search in Google Scholar
  • 18 Jani G K, Shah D P, Jain V C, Patel M J, Vithalan D A. Evaluating mucilage from Aloe barbadensis Miller as a pharmaceutical excipient for sustained-release matrix tablets.  Pharm Technol. 2007;  31 90-98
    Search in Google Scholar
  • 19 Giannola L I, De Caro V, Giandalia G, Siragusa M G, Campisi G, Florena A M, Ciach T. Diffusion of naltrexone across reconstituted human oral epithelium and histomorphological features.  Eur J Pharm Biopharm. 2007;  65 238-246
    Search in Google Scholar
  • 20 Koland M, Sandeep V P, Charyulu N R. Fast dissolving sublingual films of ondansetron hydrochloride: effect of additives on in vitro drug release and mucosal permeation.  J Young Pharm. 2010;  2 216-222
    Search in Google Scholar
  • 21 Shojaei A H, Khan M, Lim G, Khosravan R. Transbuccal permeation of a nucleoside analog, dideoxycytidine: effects of menthol as a permeation enhancer.  Int J Pharm. 1999;  192 139-146
    Search in Google Scholar
  • 22 Karnovsky M J. A formaldehyde-glutaraldehyde fixative of high osmolality for use in electron microscopy.  J Cell Biol. 1965;  27 137A-138A
    Search in Google Scholar
  • 23 Mahalingam R, Ravivarapu H, Redhkar S, Li X, Jasti B R. Transbuccal delivery of 5-aza-2-deoxycytidine: effects of drug concentration, buffer solution, and bile salts on permeation.  AAPS PharmSciTech. 2007;  8 (55) E1-E6
    Search in Google Scholar
  • 24 Heemstra L B, Finnin B C, Nicolazzo J A. Buccal mucosa as an alternative route for the systemic delivery of risperidone.  J Pharm Sci. 2010;  99 4584-4592
    Search in Google Scholar
  • 25 Hassan N, Ahad A, Ali M, Ali J. Chemical permeation enhancers for transbuccal drug delivery.  Expert Opin Drug Deliv. 2010;  7 97-112
    Search in Google Scholar
  • 26 Sandri G, Poggi P, Bonferoni M C, Rossi S, Ferrari F, Caramella C. Histological evaluation of buccal penetration enhancement properties of chitosan and trimethyl chitosan.  J Pharm Pharmacol. 2006;  58 1327-1336
    Search in Google Scholar
  • 27 Hu L, Damaj B B, Martin R, Michniak-Kohn B B. Enhanced in vitro transbuccal drug delivery of ondansetron HCl.  Int J Pharm. 2011;  404 66-74
    Search in Google Scholar
  • 28 Sandri G, Rossi S, Bonferoni M C, Ferrari F, Zambito Y, Di Colo G. Buccal penetration enhancement properties of N-trimethyl chitosan: Influence of quaternization degree on absorption of a high molecular weight molecule.  Int J Pharm. 2005;  297 146-155
    Search in Google Scholar
  • 29 Shin S, Cho C, Oh I. Enhanced efficacy by percutaneous absorption of piroxicam from the ploxamer gel in rats.  Int J Pharm. 2000;  193 213-218
    Search in Google Scholar
  • 30 Shin S, Kim J. Enhanced permeation of triamcinolone acetonide through the buccal mucosa.  Eur J Pharm Biopharm. 2000;  50 217-220
    Search in Google Scholar
  • 31 Figueiras A, Hombach J, Veiga F, Bernkop-Schnürch A. In vitro evaluation of natural and methylated cyclodextrins as buccal permeation enhancing system for omeprazole delivery.  Eur J Pharm Biopharm. 2009;  71 339-345
    Search in Google Scholar
  • 32 de Vries M E, Boddé H E, Verhoef J C, Ponee M, Craane W I H M, Junginger H E. Localization of the permeability barrier inside porcine buccal mucosa: a combined in vitro study of drug permeability, electrical resistance and tissue morphology.  Int J Pharm. 1991;  76 25-35
    Search in Google Scholar
  • 33 Madhav N V S, Shakya A K, Shakya P, Singh K. Orotransmucosal drug delivery systems: a review.  J Control Release. 2009;  140 2-11
    Search in Google Scholar
  • 34 Dorr W, Jacubek A, Kummermehr J, Herrmann T, Dolling-Jochem I, Eckelt U. Effects of stimulated repopulation on oral mucositis during conventional radiotherapy.  Radiother Oncol. 1995;  37 100-107
    Search in Google Scholar

Prof. Thirumala Govender

School of Pharmacy and Pharmacology
University of KwaZulu-Natal

Private Bag X54001, Durban

4000, KwaZulu-Natal

South Africa

Phone: +27 3 12 60 73 58

Fax: +27 3 12 60 77 92

Email: govenderth@ukzn.ac.za