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Planta Med 2009; 75(6): 587-595
DOI: 10.1055/s-0029-1185341
Pharmacology
Original Paper
© Georg Thieme Verlag KG Stuttgart · New York

Intestinal Drug Transport Enhancement by Aloe vera

Weiyang Chen1 , Zhilei Lu1 , Alvaro Viljoen1 , Josias Hamman1
  • 1Department of Pharmaceutical Science, Tshwane University of Technology, Pretoria, South Africa
Further Information

Publication History

received August 15, 2008 revised Nov. 4, 2008

accepted Dec. 14, 2008

Publication Date:
12 February 2009 (online)

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Abstract

The effect of Aloe vera (L.) Burm. f. (Aloe barbadensis Miller) gel and whole leaf extract on the permeability of Caco-2 cell monolayers was determined. Solutions of gel and the whole leaf extract were applied to the cell monolayers, and the transepithelial electrical resistance was monitored for 2 hours, which was then continued for another 2 hours after removal of the test solutions to measure reversibility of the effect. The transport of insulin in the presence and absence of the A. vera gel and whole leaf extract solutions was also investigated. Both the A. vera gel and whole leaf extract were able to significantly reduce the transepithelial electrical resistance of the Caco-2 cell monolayers at concentrations above 0.5 % w/v and thereby showed the ability to open tight junctions between adjacent cells. This effect was fully reversible, as the electrical resistance of the cell monolayers returned to the original value upon removal of the test solutions. The A. vera gel and whole leaf extract solutions significantly enhanced the transport of insulin across the Caco-2 cell monolayers compared with the control. The results suggest that these plant products have a high potential to be used as absorption enhancers in novel dosage forms for drugs with poor bioavailabilities when administered orally. On the other hand, an uncontrolled increase in the bioavailability of drugs that are taken simultaneously with A. vera gel and whole leaf extract products may result in adverse effects, and the potential exists that toxic blood plasma levels may be reached.

Key words

Aloe vera (L.) Burm. f. - Asphodelaceae - gel - whole leaf extract - absorption enhancement - Caco‐2

References

  • 1 Crowley P J, Martini L G. Formulation design: new drugs from old.  Drug Discov Today. 2004;  1 537-542
    PubMedSearch in Google Scholar
  • 2 Gomez-Orellana I. Strategies to improve oral drug bioavailability.  Expert Opin Drug Deliv. 2005;  2 419-433
    CrossrefPubMedSearch in Google Scholar
  • 3 Muranishi S. Absorption enhancers.  Crit Rev Ther Drug Carrier Syst. 1990;  7 1-33
    PubMedSearch in Google Scholar
  • 4 Salama N N, Eddington N D, Fasano A. Tight junction modulation and its relationship to drug delivery.  Adv Drug Deliv Rev. 2006;  58 15-28
    CrossrefPubMedSearch in Google Scholar
  • 5 Brayden D J, O'Mahony D J. Novel oral drug delivery gateways for biotechnology products: polypeptides and vaccines.  Pharm Sci Technol Today. 1998;  1 291-299
    CrossrefPubMedSearch in Google Scholar
  • 6 Newton L E. Aloes in habitat. Reynolds T, ed. Aloes: the genus Aloe. Washington DC; CRC Press 2004: 3-36
    Search in Google Scholar
  • 7 Reynolds T, Dweck A C. Aloe vera leaf gel: a review update.  J Ethnopharmacol. 1999;  68 3-37
    CrossrefPubMedSearch in Google Scholar
  • 8 Mascolo N, Izzo A A, Borrelli F, Capasso R, Di Carlo G, Sautebin L, Capasso F. Healing powers of aloes. Reynolds T, ed. Aloes: the genus Aloe. Washington DC; CRC Press 2004: 209-238
    Search in Google Scholar
  • 9 Talmadge J, Chavez J, Jacobs L, Munger C, Chinnah T, Chow J T, Williamson D, Yates K. Fractionation of Aloe vera L. inner gel, purification and molecular profiling of activity.  Int Immunopharmacol. 2004;  4 1757-1773
    CrossrefPubMedSearch in Google Scholar
  • 10 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
    PubMedSearch in Google Scholar
  • 11 Femenia A, Sanchez E S, Simal S, Rosello C. Compositional features of polysaccharides from Aloe vera (Aloe barbadensis Miller) plant tissues.  Carbohydr Polym. 1999;  39 109-117
    CrossrefPubMedSearch in Google Scholar
  • 12 Lee J K, Lee M K, Yun Y P. Acemannan purified from Aloe vera induces phenotypic and functional maturation of immature dendritic cells.  Int Immunopharmacol. 2001;  1 1275-1284
    CrossrefPubMedSearch in Google Scholar
  • 13 Moreira L RS, Filho E XF. An overview of mannan structure and mannan-degrading enzyme systems.  Appl Microbiol Biotechnol. 2008;  79 1-14
    CrossrefPubMedSearch in Google Scholar
  • 14 Choi S, Chung M-H. A review on the relationship between Aloe vera components and their biologic effects.  Semin Integr Med. 2003;  1 53-62
    CrossrefPubMedSearch in Google Scholar
  • 15 Ni Y, Turner D, Yates K M, Tizard I. Isolation and characterisation of structural components of Aloe vera L. leaf pulp.  Int Immunopharmacol. 2004;  4 1745-1755
    CrossrefPubMedSearch in Google Scholar
  • 16 Vinson J A, Al Kharrat H, Andreoli L. Effect of Aloe vera preparations on the human bioavailability of vitamins C and E.  Phytomedicine. 2005;  12 760-765
    CrossrefPubMedSearch in Google Scholar
  • 17 Cole L, Heard C H. 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
    PubMedSearch in Google Scholar
  • 18 Kotzé A F, Lueβen H L, De Leeuw B J, De Boer A G, Verhoef J C, Junginger H E. N-trimethyl chitosan chloride as a potential absorption enhancer across mucosal surfaces: In vitro evaluation in intestinal epithelial cells (Caco-2).  Pharm Res. 1997;  14 1197-1202
    CrossrefPubMedSearch in Google Scholar
  • 19 Junginger H E, Verhoef J C. Macromolecules as safe penetration enhancers for hydrophilic drugs: a fiction?.  Pharm Sci Technol Today. 1998;  9 370-376
    PubMedSearch in Google Scholar
  • 20 Di Colo G, Zambito Y, Zaino C. Polymeric enhancers of mucosal epithelia permeability: synthesis, transepithelial penetration enhancement properties, mechanism of action, safety issues.  J Pharm Sci. 2007;  97 1-29
    PubMedSearch in Google Scholar
  • 22 Thanou M M, Kotzé A F, Scharringhausen T, Luessen H L, De Boer A G, Verhoef J C, Junginger H E. Effect of degree of quaternization of N-trimethyl chitosan chloride for enhanced transport of hydrophilic compounds across intestinal Caco-2 cell monolayers.  J Control Release. 2000;  64 15-25
    CrossrefPubMedSearch in Google Scholar
  • 23 Borchard G, Luessen H L, De Boer A G, Verhoef J C, Lehr C –M, Junginger H E. The potential of mucoadhesive polymers in enhancing intestinal peptide drug absorption. III: Effects of chitosan-glutamate and carbomer on epithelial tight junctions in vitro.  J Control Release. 1996;  39 131-138
    CrossrefPubMedSearch in Google Scholar
  • 24 Schipper G M, Olsson S, Hoogstraate J A, De Boer A G, Varum K M, Artursson P. Chitosan as absorption enhancers for poorly absorbable drugs 2: mechanism of absorption enhancement.  Pharm Res. 1997;  14 923-929
    CrossrefPubMedSearch in Google Scholar
  • 25 Grabovac V, Föger F, Bernkop-Schnürch A. Design and in vivo evaluation of a patch delivery system for insulin based on thiolated polymers.  Int J Pharm. 2008;  348 169-174
    PubMedSearch in Google Scholar
  • 26 Kotzé A F, Luessen H L, De Leeuw B J, De Boer A G, Verhoef J C, Junginger H E. Comparison of the effect of different chitosan salts and N-trimethyl chitosan chloride on the permeability of intestinal epithelial cells (Caco-2).  J Control Release. 1998;  51 35-46
    CrossrefPubMedSearch in Google Scholar

Prof. Josias Hamman

Department of Pharmaceutical Science
Tshwane University of Technology

Private Bag X680

Pretoria 0001

South Africa

Phone: + 27 1 23 82 63 97

Fax: + 27 1 23 82 62 43

Email: hammanjh@tut.ac.za