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‘Bioavailability enhancers’ when in combination with another components, potentialize the interaction, acting as receptors and make target cells more receptive. They enhance bioavailability and bioefficacy of a particular ingredient and improve the absorption.

 

There are several mechanisms of action by which herbal bioenhancers act. Nutritional bioenhancers improve absorption by acting on gastrointestinal tract.

 

Aloe as a bioavailability enhancer

The commonly accepted definition of bioavailability is the proportion of the nutrient that is digested, absorbed and metabolized through normal pathways.

It is not enough to know how much of a nutrient is present in a dietary supplement; the more important issue is how much of that present is bioavailable.

A common belief regarding bioavailability of dietary supplements is that they have to be in solution to be absorbed in the body. As the majority of the vitamins and supplements that we consume are flushed out of our system before we are able to absorb them fully.

Aloe polysaccharides are considered the main biologically active component of Aloe that helps enhance nutrient absorption. Aloe Vera can be incorporated to any formulation as a nutritive additive into various oral, capsules, tablets, gel caps, and parenteral delivery methods such as in waters, beverages, foods, herbal, natural or dietary supplements.  Fundamentally, in many countries throughout the globe, botanicals are the first choice in preventative health, and the costs are not just monetary. Conventional healthcare is costly both monetarily and in many, depressed quality of life results due to side effects.

Aloe vera is packed full of immune-boosting polysaccharides which help the immune system to behave properly.

 

Recent research, sponsored by the International Aloe Science Council (IASC), concluded Aloe Vera increases levels of vitamins C and E in the bloodstream by more than 200 % when consumed. The study also concluded Aloe Vera can enhance the bioavailability of both water- and fat-soluble vitamins, and has a natural time-release effect (vitamin levels were found to remain elevated for 24 hours, according to the study).

Like Aloe, vitamins C and E are known to be powerful antioxidants that boost immune system function, promote skin health, and protect cardiovascular health. The bioavailability research has created a landmark event and major turning point for the functional food and nutraceutical industry as these companies realize the benefits of incorporating Aloe Vera into their products containing vitamins C and E.

Aloe Vera gel enhance the bioavailability of vitamins C and E in humans, and also is able to significantly reduce transepithelial electrical resistance (TEER) of Caco-2 cell monolayers and also significantly enhanced the transport of insulin across this cell culture model. The transport enhancement effect of Aloe Vera materials is probably due to the opening of tight junctions to allow paracellular transport, Aloe Vera’s polysaccharides contributes on their drug absorption enhancing properties.  The effect of Aloe Vera on the oral bioavailability of vitamins C and E was investigated in humans in a randomised, double-blind, cross-over clinical trial. Both the gel and aloe vera gel extract decreased the rate of vitamin C absorption, but the overall bioavailability (area-undercurve) of vitamin C was 3 times higher when administered with the Aloe gel as compared to the control and the gel kept the level of this vitamin significantly higher (p ≤ 0.05) than the Vaseline even after 24 hours.  The mechanism of action of the Aloe products to improve the bioavailability of the vitamins was explained to be a possible protection effect against the degradation of the vitamins in the intestinal tract as well as binding of the polysaccharides to the vitamins and thereby slowing down the absorption rate. Many potential therapeutic agents face the disadvantage of low bioavailability after oral administration due to poor membrane permeability. Drug absorption enhancers are compounds capable of reversibly removing the resistance of the outer layers in the body with minimum tissue damage, thus allowing the drug to enter the blood circulation in sufficient quantities.

“Maintaining a strong immune system is the body’s best defense”

In addition to washing our hands, wearing a mask, and keeping our distance, the best way to fight Covid-19 would be to keep our immune system in top condition.

To achieve this stable and effective immune system, several measures must be taken, like eat healthy, doing physical exercise and supplementing with science-based immunomodulators.

 Aloe Vera is a very well-known adaptogen.

An adaptogen is something that boosts the body’s natural ability to adapt to external changes and resist illness. It is thought that Aloe’s power as an adaptogen balances the body’s system, stimulating the defense and adaptive mechanisms of the body. This allows you an increased ability to cope with stress (physical, emotional and environmental stress like pollution). Aloe Vera’s most extraordinary property, the ability to act appropriately on the specific problem or problems of the person using it. People taking Aloe Vera for one problem are often surprised when it handles something else.

Immune modulation of Aloe Vera

Carbohydrate-based immuneadjuvants are capable of enhancing the vaccine against various infectious disease. Several natural polysaccharides originating from plants and microbes have been tested for their adjuvant potential. Adjuvant potential of plant polysaccharides mainly depends upon their solubility, molecular weight, degree of branching and the conformation of carbohydrate structural backbone. Aloe polysaccharide or acemannan as an adjuvant may interact and activate various toll-like receptors and inflammasomes, involving several innate immune system players in the ensuing immune response. Aloe polysaccharide or acemannan plays critical roles in immune system function and has strong safety and torelability records and is readily biodegradable.

Aloe’s polysaccharides contribute on drug absorption, enhancing properties

One function of epithelial cells is to maintain distinct compartments within the body and also to act as barriers to separate the body from the external environment. Although molecules can cross the intestinal epithelium by three main pathways, namely transcellular passive diffusion, paracellular passive diffusion and carrier-mediated transport, many useful drugs exhibit poor absorption after oral administration.

Poor drug absorption across the intestinal epithelium is in many cases attributed to unfavourable physico-chemical properties of the drug molecule such as hydrophilicity and a large molecular weight. The intestinal absorption of these drugs can be increased by different techniques such as co-administration of absorption enhancing agents. Absorption enhancing agents may facilitate the absorption of poorly absorbable drugs by different mechanisms such as opening of tight junctions or changing the membrane structure or targeting transporter proteins.

Only limited information is currently available on the drug absorption enhancement activities of Aloe vera gel, but if it proves to be a safe and effective absorption enhancer in vivo, it could be used in novel dosage forms for the oral delivery of poorly absorbable drugs that are administered by means of injections.

Aloe Vera and TEER

Aloe Vera and Effect on biological membrane permeation and Intestinal drug absorption enhancement.  The polysaccharides in the Aloe Vera are responsible to contribute to a large extent to the effect on the TEER of the excised rat intestinal tissue. This reduction in TEER of the excised rat intestinal.  Tissue by the Aloe Vera indicates their ability to open the tight junctions between epithelial cells, which indicate the potential of these materials to enhance drug transport across intestinal tissues.  TEER is a measure of tight junction integrity between adjacent intestinal epithelial cells. If the size of the openings of the tight junctions increases in the presence of a paracellular permeability enhancer, the TEER of the intestinal epithelium will be reduced because of the increasing flow of ions through the opened tight junctions and intercellular spaces. Tight junctions between epithelial cells are dynamic structures that can be modulated by certain chemicals in such a way to enlarge the pores or fenestrae and thereby allow paracellular passage of hydrophilic macromolecules. This approach to drug absorption enhancement has the additional Advantage of avoiding enzymatic degradation of susceptible molecules. Aloe Vera Compounds selectively open the intestinal epithelial tight junctions, referred to as paracellular permeability enhancers, have shown potential as novel excipients in advanced drug delivery systems. It is well known that polysaccharides of natural origin such as Aloe Vera are capable of enhancing the intestinal absorption of co-administered drugs by means of a transient opening of the tight junctions between adjacent epithelial cells to allow for paracellular transport across the intestinal epithelium. Aloe Vera Gel Extract could decrease the transepithelial electrical resistance of intestinal epithelial cell monolayers (Caco-2), thereby indicating opening of the tight junctions between adjacent epithelial cells. Aloe Vera Gel is also able to significantly increase the transport of the macromolecular peptide drug, insulin, across the Caco-2 cell monolayers.

If consumers put good things into their bodies, they are more likely to feel

better and maintain a healthier body. What is now being explored—fueling the growth of wellness from within.

AMB WELLNESS offers active & excipient Aloe Vera Ingredients with key points of value for Nutra & pharma applications. Aloe Vera is an excellent carrier and excipient for food supplements, sport nutrition, food fortification, fortified premixes, nutraceuticals & animal health. Aloe Vera is an ingredient that will surely be of the interest in companies manufacturing tablets, softgels, hard capsules, powders and functional drinks.

Aloe’s polysaccharides contribute to drug absorption due to their enhancing properties. Currently, the new trend in Aloe Vera Global Market is using Aloe Vera for Nutraceuticals as a vehicle for other functional ingredients enhancing their bioavailability instead of using other carriers that will not contribute at all to the better absorption of the other ingredients, nowadays Aloe Vera can be found mixed with other actives such as vitamins, minerals amino acids, botanical extracts and so on.

Manufacturers and marketers would be wise to understand that dosage forms for delivery of these ingredients can make as big a difference in consumer satisfaction as the ingredients themselves. In fact, delivery forms can maximize the potential benefit of those ingredients. Today’s busy consumers look for easy-to-use formats. Healthy lifestyle consumers are also hungry for anything they perceive to be “good for preventing illness.

REFERENCES: Aloe a bioenhancer, immunomodulatory

 

1. Fast Dissolving Tablets of Aloe Vera Gel.Jyotsana Madan1, AK Sharma2, Ramnik Singh3 1UP Technical University, Lucknow , India, 2MJP Rohilkhand, University, Bareilly,India, 3Sri Sai College of Pharmacy, Pathankot, India 2. Aloe gel and whole-leaf raw materials: Promising excipients for the production of matrix-type tablets Tafara Jambwa, Alvaro Viljoen and Josias Hamman Department of Pharmaceutical Sciences, Tshwane University of Technology, Private Bag X680, Pretoria, 0001, South Africa
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4. Design, formulation and evaluation of Aloe vera chewing gum. Abolfazl Aslani1, Alireza Ghannadi2, Razieh Raddanipour11 Department of Pharmaceutics, School of Pharmacy and Novel Drug Delivery Systems Research Cente, Isfahan, Iran
5. Aloe vera Mucilage as Solubility Enhancer in Tablet Formulation. Habibur Rahman*, Telny Thomas Chungath,

Kuppusamy Selvakumaraswa y and Chandrasekar R. PSG College of Pharmacy, Coimbatore, Tamil Nadu, India.

7. Growing impact of Herbal Bioenhancers in Pharmaceutical Industries: A Comprehensive Review Faiza Asghar School of Biological Sciences-University of the Punjab Lahore, Pakistan.
8. Evaluating Mucilage from Aloe Barbadensis Miller as a Pharmaceutical Excipient for Sustained-Release Matrix Tablets. Nov 02, 2007 By Vineet C. Jain, Girish K. Jani, Manish J. Patel, Disha A. Vithalani, Dhiren P. Shah
9. Evaluation of Aloe debrana Leaf Mucilage as a Sustained Release Matrix Former in Tablets Semaw Asmare1 *, Anteneh Belete2 and Tsige Gebre-Mariam2
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15. Vinson, J.A.; Al Kharrat, H.; Andreoli, L. Effect of Aloe vera preparations on the human b ioavailability of vitamins C and E. Phytomedicine 2005, 12, 760-765.
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a pharmaceutical excipient for sustained-release matrix tablets. Pharm. Technol. 2007, 31, 90-98.

17. Steenkamp, V.; Stewart, M.J. Medicinal applications and toxicological activities of Aloe products. Pharm. Biol. 2007, 45, 411-420.
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In situ and in vivo efficacy of peroral absorption enhancers in rats and correlation to in vitro mechanistic studies. Il Farmaco 2005, 60, 874-883.

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23.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.

24. Hadgraft, J. Passive enhancement strategies in topical and transdermal drug delivery. Int. J. Pharm. 1999, 184, 1-6.
25. Moser, K; Kriwet, K.; Naik, A.; Kalia, Y.N.; Guy, R.H. Passive skin penetration enhancement and its quantification in vitro. Eur. J. Pharm. Biopharm. 2001, 52, 103-112.
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27. Formulation evaluation and in-vitro drug release characteristics of aloe vera herbal suppositories Tarkase K. N. and Danve A. V.* Department of Quality Assurance Technique, Padmashree Dr. Vitthalrao Vikhe Patil Foundations College of Pharmacy, Viladghat, Ahmednagar, Maharashtra, India.
28. Extended Drug Release Retarding Effect of Aloe vera Gel IN THE DESIGN OF TABLET DOSAGE FORM Bharath Kumar. N, S. Bharath* , R. Deveswaran, B.V. Basavaraj, V. Madhavan Department of Pharmaceutics, M. S. Ramaiah College of Pharmacy, M.S.R.Nagar, M.S.R.I.T. Post, Bangalore-54, India.
29. ALOE VERA POWDER BASED MATRIX TABLET FOR ORAL CONTROLLED DELIVERY OF HIGHLY SOLUBLE DRUG ANURUPA C, SUSEEM S.R* Pharmaceutical Chemistry Division, School of Advance Sciences, VIT University, Vellore-632014, Tamil Nadu, India.
30. Comparison of Aloe Vera Gel and Aloe Vera Powder on Physical Properties of Ranitidine Mucoadhesive Microgranules Endang Diyah Ikasari*, Anang Budi Utomo, Hanny Setyowati Department of Pharmaceutical Sciences, College of Pharmacy, “Yayasan Pharmasi”, Semarang, Indonesia
31. Design and Development of Dental Film Containing Aloe vera for the Treatment of Human Periodontal Diseases. Himansu Bhusan Samal1*, Itishree Jogamaya Das1, Ch. Niranjan Patra2, P. N. Murthy3
32. DEVELOPMENT AND EVALUATION OF GLIMEPIRIDEALOE BARBADENSIS MUCILAGE CONTROLLED RELEASE MATRIX TABLETS HINDUSTAN ABDUL AHAD∗, J.SREERAMULU a, V. HIMA BINDUb and N. KIRANMAYI
33. Effect of Vehicles on Topical Application of Aloe Vera and Arnica Montana Components Valentina Bergamante, Gian Carlo Ceschel, Sergio Marazzita, Celestino Ronchi & Adamo Fini
34. Natural Excipients- A Review S. Dharmendra *1 , J.K. Surendra2, M.Sujata3 , S. Shweta1
35. THE EFFECT OF ALOE VERA POWDER (Aloe vera (L.) Webb) ON PHYSICAL PROPERTIES OF MUCOADHESIVE MICROGRANULES CONTAINING RANITIDINE HYDROCHLORIDE Endang Diyah Ikasari*, Anang Budi Utomo, Hanny Setyowati, Salasa Ayu Trisnawati Yayasan Pharmasi College of Pharmacy, Letjen Sarwo Edhie Wibowo Km 1. Pucanggading Semarang 50193, Indonesia
36. Liposomal Aloe vera trans-emulgel drug delivery of naproxen and nimesulide: A study. Panuganti Venkataharsha, Ellutla Maheshwara, Y Prasanna Raju,1 Vayalpati Ashok Reddy,1 Bandugalla Sanjeev Rayadu,1 and Basappa Karisetty
37. DESIGN AND EVALUATION OF SUSTAINED RELEASE MATRIX TABLETS OF GLIMEPIRIDE BASED ON COMBINATION OF NATURAL AND SYNTHETIC POLYMERS Hindustan Abdul Ahad1 , Sreeramulu J2 , Hima Bindu V3 , Chitta Suresh Kumar1 , Kishore Kumar Reddy B1 , Chandana Rekha V1 , Sivaji S4 1College of pharmacy, Sri Krishnadevaraya University, Anantapur, Andhra Pradesh, India 2Depatment of Chemistry, Analytical Lab, Sri Krishnadevaraya University, Anantapur, Andhra Pradesh, India
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39. INVESTIGATING THE POTENTIAL OF ALOE VERA AS PENETRATION ENHANCER FOR TRANSDERMAL DELIVERY KIRAN SHARMA1*, ASHU MITTAL2 , SHEIKH MURTUZA3 & PRIYANKA AGRAHAR
40. Study and description of hydrogels and organogels as vehicles for cosmetic active ingredients M. E. MORALES, V. GALLARDO, B. CLARÉS, M. B. GARCÍA, and M. A. RUIZ, Pharmacy and Pharmaceutical Technology Department, School of Pharmacy, University of Granada, 18071 Granada, Spain
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43. Formulation of Aloe vera polysaccharide gel niosomes Sasan Khadem nematollahi1 , Abbas Pardakhty2, Kobra Habibi3 , Mitra Mehrabani3
44. Aloe Vera as Penetration Enhancer. Kiran Sharma*, Ashu Mittal, Nitesh Chauhan Assistant professor at KIET School of Pharmacy, 13km stone, Ghaziabad – Meerut road, Ghaziabad
45. Microencapsulation of natural antioxidant powder from Aloe vera (L.) skin using foam mat drying method.

1,2*Narsih, 2 Sri Kumalaingsih, 2 Susinggih Wijana and 2Wignyanto 1 Department Agricultural Technology, Pontianak State Polytechnic, Jalan Ahmad Yani, Pontianak, Kalimantan Barat, Indonesia 78124 2 Department Agroindustrial Technology, Faculty of Agricultural Technology, Brawijaya University, Jalan Veteran Malang, Jawa Timur, Indonesia 65145

46. Carbopol and Sodium Carboxymethylcellulose Based Methylsulfonylmethane Gels for Treatment of Osteoarthritis: In-vitro and In-vivo Evaluation ,. Authors and affiliation (s): Vishwajeet Ghorpade*, Kailas Mali, Remeth Dias and Prashant Karande Satara College of Pharmacy, Behind Spicer India Ltd., Degaon, Satara, Maharashtra, India, 415004.
47. Natural Bioenhancers: Current Outlook Srinivasan Shanmugam* Pharm. R&D Institute, Hanmi Pharm. Co., Ltd., Hwaseung-Si, Gyeonggi-Do, 445-913, Korea Srinivasan Shanmugam Ph.D., Pharm. R&D Institute Hanmi Pharm. Co., Ltd., Hwaseung-Si Gyeonggi-Do, 445-913, Korea
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51. Liposomes encapsulating Aloe vera leaf gel extract significantly enhance proliferation and collagen synthesis in human skin cell lines. M Takahashi, D Kitamoto, Y Asikin, K Takara
52. Evaluation of biological properties and clinical effectiveness of Aloe vera: A systematic review. Maharjan H. Radha, Nampoothiri P. Laxmipriya,
53. In-Vitro Assessment and Pharmacodynamics of Nimesulide Incorporated Aloe vera Transemulgel. Authors: Vandana, KR; R. Yalavarthi, Prasanna; Sundaresan, CR; N. Sriramaneni, Raghava; C. Vadlamudi, Harini
54. In vitro drug permeation enhancement potential of aloe gel materials. T Lebitsa, A Viljoen, Z Lu, J Hamman – Current drug delivery, 2012 – ingentaconnect.com
55. Aloe Vera High Molecular Weight Fractions as Carbohydratebased Immune Adjuvants. A Yagi – Journal of Gastroenterology and Hepatology Research, 2013 – ghrnet.org
56. Paracellular drug absorption enhancement through tight junction modulation. Hendrik JR Lemmer & Josias H Hamman , PhD
57. Skin Permeation of Candesartan Cilexetil from Transdermal Patch Containing Aloe Vera Gel as Penetration Enhancer.K Sharma – Asian Journal of Pharmaceutics (AJP)
58. DRUG ABSORPTION ENHANCING PROPERTIES OF ALOE VERA ACROSS INTESTINAL EPITHELIUM. W Chen, J Hamman, A Vlijoen – African Journal of Traditional, …, 2009
59. Intestinal drug transport enhancement by Aloe vera. W Chen, Z Lu, A Viljoen, J Hamman – Planta Medica, 2010

60.Possible Prophylaxes of Aloe Vera Juice with CoQ10 to Enhance Muscle Performance. A Yagi, S Ataka – Journal of Gastroent rology and Hepatology Research, 2016 –

61. Skin permeation enhancement potential of Aloe Vera and a proposed mechanism of action based upon size exclusion and pull effect. Louise Cole, Charles Heard.
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64. Polymeric Plant-derived Excipients in Drug Delivery. Carien E. Beneke, Alvaro M. Viljoen and Josias H. Hamman * Department of Pharmaceutical Sciences, Tshwane University of Technology, Private Bag X680, Pretoria, 0001, South Africa
65. Exploring the Potential of Gastro Retentive Dosage Form in Delivery of Ellagic Acid and Aloe vera Gel Powder for Treatment of Gastric Ulcers. Authors: N Ranade, Arati; S. Ranpise, Nisharani; Ramesh, C.
66. Release characteristics of Aspirin and Paracetamol drugs from tablets with Aloe Vera gel powder as a drug carrier. K. Subramanian* , S.Narmadha, U.Vishnupriya & V.Vijayakumar
67. Aloe gel and whole-leaf raw materials: Promising excipients for the production of matrix-type tablets. Tafara Jambwa, Alvaro Viljoen, Josias Hamman

68.Matrix forming excipients from natural origin for controlled release matrix type tablets. T. Jambwa1, A. Viljoen1, J. Hamman1, 2, ,

69. Matrix forming excipients from natural origin for controlled release matrix type tablets. T. Jambwa1, A. Viljoen1, J. Hamman1, 2. Matrix forming excipients from natural origin for controlled release matrix type tablets. T. Jambwa1, A. Viljoen1, J. Hamman1, 2, ,
70. Efficacy and safety of Aloe vera syrup for the treatment of gastroesophageal reflux disease: a pilot randomized positive-controlled trial. Panahi Y, Khedmat H, Valizadegan G, Mohtashami R, Sahebkar A.

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56. Packaged Facts, 2014. Functional Foods. February.
57. Packaged Facts, 2014. Formulation Trends: Ingredients Consumers Avoid. February
58. 2014c. Healthy Eating Consumer Trend Report. Technomic, Chicago. www.technomic.com.
59. Jacobsen, J. 2015. “2015 New Product Development Outlook.” Beverage Industry 106(1): 56, 58-60, 62, 64, 65.
60. Wyatt, S. Lyons. The State of Snacking. IRI Summit Presentation. Austin TX. March 31,2015. iriworldwide.com.
61. Hartman Group, 2015. Health & Wellness.
62. NRA, 2014. What’s Hot Chef Survey? National Restaurant Assoc., Washington, D.C. org.
63. 2014. Statistics: Sports and Exercise 2013. National Sporting Goods Assoc., North Palm Beach, FL. www.nsga.org.

64. Cosgrove, MC, et al. Dietary nutrient intake and skin aging appearance among middle-aged American women. Am J Clin Nutr 2007;86:1225-1231.
65. Kim, Hyeon Ho, et al. “Eicosapentaenoic acid inhibits UV-induced MMP-1 expression in human dermal fibroblasts.” Journal of Lipid Research 46.8 (2005): 1712-1720.
66. Asserin, Jérome, et al. “The effect of oral collagen peptide supplementation on skin moisture and the dermal collagen network: evidence from an ex vivo model and randomized, placebo-controlled clinical trials.” Journal of Cosmetic Dermatology 14.4 (2015): 291-301.
67. Proksch E, et al. Oral intake of specific bioactive collagen peptides reduces skin wrinkles and increases dermal matrix synthesis. Skin Pharmacol Physiol 2014;27: 113-119.
68. Perricone, N. Archives of Gerontology and Geriatrics, July-August 1999; vol 29.
69. Kawada, Chinatsu, et al. “Ingested hyaluronan moisturizes dry skin.” Nutrition Journal 13.1 (2014): 1.
70. Aust O, Stahl W, Sies H, et al. Supplementation with tomato-based products increases lycopene, phytofluene, and phytoene levels in human serum and protects against UV-light-induced erythema. Int J Vitam Nutr Res 2005;75:54-60.
71. Floersheim, GL. Treatment of brittle fingernails with biotin. Z. Hautkr. 1989: 64(1):41-48.
72. Hochman LG, Scher RK, Meyerson MS. Brittle nails: response to daily biotin supplementation. Cutis. 1993: 51(4): 303-305.
73. Boccaletti, V. & Zendri E. et al. Familial Uncombable Hair Syndrome: Ultrastructural Hair Study and Response to Biotin. Pediatr Dermatol. 2007: 24(3): E14-16.
74. References of intake aloe vera as food supplement

Digestive Health

1. McKeith, Gillian.  Gillian McKeith’s Living Food for Health: 12 Natural Superfoods to Transform Your Health.North Bergen, NJ: Basic Health Publications, 2005. Print.
2. Surjushe A, Vasani R, Saple DG. ALOE VERA: A SHORT REVIEW.Indian Journal of Dermatology. 2008;53(4):163-166. doi:10.4103/0019-5154.44785.
3. Yun JM1, Singh S, Jialal R, Rockwood J, Jialal I, Devaraj S. A randomized placebo-controlled crossover trial of aloe vera on bioavailability of vitamins C and B(12), blood glucose, and lipid profile in healthy human subjects.J Diet Suppl. 2010 Jun;7(2):145-53. doi: 10.3109/19390211003781693.
4. Surjushe, Amar, Resham Vasani, and D G Saple. ALOE VERA: A SHORT REVIEW.Indian Journal of Dermatology 53.4 (2008): 163–166. PMC. Web. 25 Feb. 2016.
5. Gullón B1, Gullón P, Tavaria F, Alonso JL, Pintado M. In vitro assessment of the prebiotic potential of Aloe vera mucilage and its impact on the human microbiota.Food Funct. 2015 Feb;6(2):525-31. doi: 10.1039/c4fo00857j.
6. Coats, Bill C., and Robert Ahola. Aloe Vera: The New Millennium: The Future of Wellness in the 21st Century.New York: IUniverse, 2003. Print.
7. Eamlamnam K1, Patumraj S, Visedopas N, Thong-Ngam D. Effects of Aloe vera and sucralfate on gastric microcirculatory changes, cytokine levels and gastric ulcer healing in rats.World J Gastroenterol. 2006 Apr 7;12(13):2034-9.
8. Zihong L, et al. The curative effect of aloe on constipation and its primary mechanism.Quangdong Medical Journal. October 2005.
9. Langmead, L. (2004). Full text: Randomized, double-blind, placebo-controlled trial of oral Aloe Vera gel for active ulcerative colitis.Alimentary Pharmacology & Therapeutics, 19(7), 739–747.
10. Yongchaiyudha S, et al. Antidiabetic activity of Aloe Vera juice. I Clinical trial in new cases of diabetes mellitus.Phytomedicine 1996; 3,3:241-243.
11. Rajasekaran S, et al. Beneficial effects of Aloe Vera leaf gel extract on lipid profile status in rats with streptozotocin diabetes.Clin Exp Pharmacol Physiol. 2006 Mar;33(3):232-7.
12. Cowan D. Oral Aloe Vera as a treatment for osteoarthritis: A summary.Br J Community Nurs. 2010 Jun;15(6):280-2.
13. Galal EE; Kandil A; Hegazy R; El Ghoroury M; Gobran W: Aloe vera and gastrogenic ulceration. J Drug Res Egypt 7:73-77, 1975.
14. Kandil A; Gobran W: Protection of gastric mucosa by Aloe vera. J Drug Res Egypt 11: 191-6,1979.
15. Kandel A; Gbran W: Protection of gastric mucosa by Aloe vera. Journal of Drug Research 11:191-196, 1979 (Egypt).
16. Evaluation of Acemannan in the treatment of recurrent aphthous stomatitis. Wounds 1994; 6: 40-45. Plemons JM, Rees TD, Binnie WH, et al
17. Protection of gastric mucosa by Aloe vera Kandil A.; Gobran W. Nat. Org. Drug Cont. Res., Giza EGYPT DRUG RES. (EGYPT) , 1979, 11/12 (191196)
18. Aloe vera and gastrogenic ulceration Galal E.E.; Kandil A.; Hegazy R.; et al.
    Drug Res. Contr. Cent., Giza EGYPT  DRUG RES.(U.A.R.) (EGYPT) , 1975, 7/2 (7378)
19. Aloe vera in treatment of refractory irritable bowel syndrome: Trial on Iranian patients
20. Hossein Khedmat,1,2 Ashraf Karbasi,2 Mohsen Amini,2 Aghdas Aghaei,2 and Saeed Taheri3

Healthier Immune System

1. Complex carbohydrates in development as human pharmaceuticals Simon P.M. Neose Pharmaceuticals Inc., 102 Witmer Rd, Horsham, PA 19044 USA EXPERT OPIN. INVEST. DRUGS (United Kingdom) , 1994, 3/3 (223239)
2. On the isolation of immunostimulatory active acemannan from Aloe barbadensis Mabel Alonso, Yanet Támbara, Matilde López, Julio C Aguilar, Orestes Mayo, Enrique Prieto, José Cremata, Gerrit Gerwig, Hans Kamerling, Eugenio Hardy
3. The broad spectrum of immunopharmacological activities of glucan includes not only the modification of certain bacterial, fungal, viral, and parasitic infections, but also inhibition of tumor growth.” Nicholas DiLuzio, Ph.D., Department of Physiology Tulane University School of Medicine
4. Harvard, Tulane, Baylor, McGill, University of California, Duke, Washington, the Armed Forces Radiology Research Institute, and other institutions all demonstrate the high immune activating properties and cholesterol lowering properties of Beta glucans.
5. Chemical and Biological characterization of a polysaccharide biological response modifier from Aloe vera.Glycobiology14 (6):501, 2004
6. Pittman, J. C. (1992). Immune enhancing effects of Aloe. Health Conscious,13(1), 2830.
7. Ivan E. Danhof, Ph.D., M.D. Immunomodulatory and Protective Action of Aloe arborescens and Aloe barbadensis (Aloe vera)
8. Reginald McDaniel, M.D. The Molecular Biology of How Dietary Supplements Support Optimal Human Health
9. The Carboxietilgermanio sesquioxide (Ge-132) or organic Germanium has different biological activities and is suitable for many diseases. Its activity as an immunomodulator is very important. The production of NK cells  increases and the result is an activation of the immune system by destroying all  tumor and abnormal cells .References:McMahon, M.; Regan, F.; Hughes, H.; Food Chemistry ,97 , 411–417, 2006.Hui, R. H.; Hou, D. Y.; Guan, C. X.; Spectroscopy and Spectral Analysis , 24, 1106-1109, 2004.
10. The acemanan is the main polysaccharide gel of Aloe vera. The glycosidic bond β- (1 → 4) of acemanan is crucial for the therapeutic effects of Aloe vera gel because humans lack the ability to break enzymatically these bonds. In addition to its properties as a cellular regenerator, healing and toning, this compound is attributed gastrointestinal immunostimulating, antiviral, and antineoplastic  properties.References: Hamman, J. H.; Molecules, 13, 1599-1616, 2008
11. The Aloe-emodin (product of oxidation of aloin) is the main representative of this family of compounds in Aloe vera. In this compound are attributed various biological properties, including antiviral, antimicrobial and hepatoprotective.Another recently discovered activity  is the anticancer property ,against neuroectodermal tumors, lung squamous carcinoma cells, human hepatoma cells, gastric carcinoma lines (AGS, NCI-N87) and cell lines and human colon cancer (DLD-1, WiDr) References:Chen, S. H.; Lin, K. Y.; Chang, C. C.; Fang, C. L.; Lin, C. P.; Food and Chemical Toxicology, 45, 2296-2303, 2007 Lin, K. Y.; Uen, Y. H.; Oncology Letters , 1, 541-547, 2010
12. In one study, new derivatives were synthesized water-soluble natural aloe emodin compound 4 (j) in an attempt to improve anticancer activity and to explore structure-activity relationships. Assays of cell growth inhibition revealed that aloe-emodin derivatives 4d, 4f y4i effectively decreased growth HepG2 (human liver cancer cells) and NCI-H460 (human lung cancer cells). Furthermore, some of the derivatives exhibit antitumor activity against comparable HeLa (human epithelial carcinoma cells) and PC3 (prostate cancer cells). References: Thimmegowda NRand cols,. Chem Biol Drug Des. 2014 Oct 17.
13. In this review the composition, action and clinical applications  of acemanan (polysaccharide from Aloe vera) is presented, and its effectiveness as an adjunct in the treatment of diseases. A total of 50 titles, resumes and studies were selected . Acemanan has several medicinal properties as osteogenic, anti-inflammatory and anti-bacterial , that accelerate healing of injuries. Additionally, acemannan has antiviral and antitumor activities in vivo via activation of the immune response. It is concluded that Aloe vera has immense potential as a therapeutic agent References: Sierra-García GD, Castro-Ríos R, González-Horta A, Lara-Arias J, Chávez-Montes A. Nat Prod Commun.2014 Aug;9(8):1217-21.
14. Among various natural medicines, Aloe vera gel showed a consistently good inhibition against Enterococcus faecalis in an in vitro study looking dentin shavings collected at depths of 200 and 400 microns. References: Bhardwaj A1, Ballal S, Velmurugan N. J Conserv Dent.2012 Jul;15(3):293-7.
15. Leishmaniasis is one of the major protozoan disease that threatens the lives of 350 million people worldwide. However, treatment options for the disease are limited. In the present study, the antiprotozoal activity of latex obtained  from Aloe was evaluated by in vitro tests against Leishmania major and Leishmania aethiopica. It was found that the latex has moderate activity against both parasites. The phytochemical research resulted in the isolation of three anthrones identified as aloinoside, aloin, and microdontina. Isolated compounds showed strong antileishmanial activity .The results indicate that the isolated compounds have the potential to be used as a scaffold for the development of safe antileishmaniales agents. References: Abeje F1, Bisrat D, Hailu A, Asres K.. Phytother Res.2014 Jul 28.
16. t’ Hart LA; van Enckevort PH; van Dijk H; Zaat R; de Silva KTD; Labadie RP:Two functionally and chemically distinct immomodulatory compounds in the gel of Aloe vera. J Ethnopharmacol 23: 61-71, 1988.
17. t’ Hart LA; vanden Berg AJJ; Kuis L; van Dijk H; Labadie RP: An anti-complementary polysaccharide with immunological adjuvant activity from the leaf parenchyma gel of Aloe vera. Plant Med 55: 509-512, 1989.
18. Karaca K; Sharma JM; Norgren R 1995: Nitric Oxide production by chicken macrophages activated by Acemannan.Int. J. Immuno pharmacol. 17 (3) 183-8.
19. t’Hart LA; Van Den Berg AJ; Klus L; Van Dijk; Labadle RP 1989: An anti-complimentary polysaccharide with immunological adjuvant activity from the leaf parenchyma gel of Aloe vera. Planta Med 55 (6) 509-12.
20. Pittman JC 1992: Immune enhancing effects of Aloe. Health Conscious 13 (1) 28-30.
21. Winters WD: Aloe Substances: Effects on Cell Growth and Immune Function. Fourth Academic/Industry Joint Conference, October 18-21, 1992; Abstract #13, page 40.
22. Chemical characterization of the immunomodulating polysaccharide of Aloe vera L.Carbohydr Res.2005 May 2;340(6):1131-42 Tai-Nin Chow J, Williamson DA, Yates KM, Goux WJ.
23. An anticomplementary polysaccharide with immunological adjuvant activity from the leaf parenchyma gel of Aloe vera ‘T Hart L.A.; Van den Berg A.J.J.; Kuis L.; Van Dijk H.; Labadie R.P. Department of Pharmacognosy, Faculty of Pharmacy of the State University of Utrecht, Catharijnesingel 60, 3511 GHUtrecht Netherlands PLANTA MED. (Germany, Federal Republic of) , 1989, 55/6 (509512)
24. Determination of the position of the Oacetyl group in a beta(1 right arrow 4)mannan (acemannan) from Aloe barbardensis Miller Manna S.; McAnalley B.H. C. Pepper Inst. Aging/Therap. Res., Florida Institute of Technology, 150 West University Boulevard, Melbourne, FL 329016988 USA CARBOHYDR. RES.(Netherlands) , 1993, 241/ (317319)
25. Activation of a mouse macrophage cell line by acemannan: the major carbohydrate fraction from Aloe vera gel. Zhang L, Tizard IR. Department of Veterinary Pathobiology, Texas A & M University CollegeStation 77843, USA.
26. Acemannan, a beta-(1,4)-acetylated mannan, induces nitric oxide production in macrophage cell line RAW 264.7. Ramamoorthy L, Kemp MC, Tizard IR. Department of Veterinary Pathobiology, Texas A & M University, College Station 77843, USA.
27. Double-blind placebo-controlled pilot trial of acemannan in advanced human immunodeficiency virus disease. Montaner JS, Gill J, Singer J, Raboud J, Arseneau R, McLean BD, Schechter MT, Ruedy J. Canadian HIV Trials Network, St. Paul’s Hospital/University of British Columbia, Vancouver, Canada
28. The impact of acemannan on the generation and function of cytotoxic T-lymphocytes.
29. Womble D, Helderman JH. Department of Internal Medicine, Vanderbilt University, Nashville, Tennessee 37232-2372.
30. Modified Aloe barbadensis polysaccharide with immunoregulatory activity. Qiu Z, Jones K, Wylie M, Jia Q, Orndorff S. Department of Drug Discovery and Screening, Univera Pharmaceuticals, Inc., Broomfield, CO, USA. jqiu@upi1.com
31. Zhang L, Tizard IR. Activation of a mouse macrophage cell line by acemannan: the major carbohydrate fraction from Aloe vera gel.Immunopharmacol. 1996;35(2):119-28.
32. Enhancement of Allo-Responsive of Human Lymphocytes by Acemannan (Carrisym). Int. J Immunopharmacol. 10 (8) 967-974.
33. The biological activities of mannans and related complex carbohydrates Ian R. Womble D; Helderman JH 1988: Tizard, BVMS, PhD, Robert H. Carpenter, DVM, MS, t Bill H. McAnalley, PhD and Maurice C. Kemp, P Department of Veterinary Microbiology and Parasitology, College of Veterinary Medicine. Texas A&M University, College Station, TX, and t Carrington Laboratories, Inc. Irving, TX, USA
34. A molecular mechanism of recognition between cell surface sugars and lectins in the phagocytosis of bacteria. Infect Immunol 1988; 56:539-47. Ofek I. Sharon N. Lectinophagocytosis:
35. Chow, J.T-N.; Williamson, D.A.; Yates, K.M.; Goux, W.J. Chemical characterisation of the immunomodulating polysaccharide of Aloe vera L. Carbohydr. Res. 2005, 340, 1131-1142.
36. Im, S-A.; Oh, S-T.; Song, S.; Kim, M-R.; Kim, D-S.; Woo, S-S.; Jo, T.H.; Park, Y.I; Lee, C-K. Identification of optimal molecular size of modified Aloe polysaccharides with maximum immunomodulatory activity. Int. Immunopharmacol. 2005, 5, 271-279.
37. Zhang, L.; Tizard, I.R. Activation of a mouse macrophage cell line by acemannan: The major carbohydrate fraction from Aloe vera. Immunopharmacology 1996, 35, 119-128.
38. Im SA, et al. In vivo evidence of the immunomodulatory activity of orally administered Aloe Vera gel.Arch Pharm Res. 2010 Mar;33(3):451-6.
39. Acemannan, an extracted polysaccharide from Aloe vera: A literature review. Sierra-García GD, Castro-Ríos R, González-Horta A, Lara-Arias J, Chávez-Montes A. Nat Prod Commun. 2014 Aug;9(8):1217-21. Review.

Absorption/Bioavailability

1. Effect of Aloe vera preparations on the human bioavailability of vitamins C and E J.A. Vinson, H. Al Kharrat, L. Andreoli Department of Chemistry, University of Scranton, Scranton, PA, 18510 4626, USA
2. Coviello, T.; Matricardi, P.; Marianecci, C.; Alhaique, F. Polysaccharide hydrogels for modified release formulations. J. Control. Release 2007, 119, 5-24.
3. Junginger, H.E.; Verhoef, J.C. Macromolecules as safe penetration enhancers for hydrophilic drugs: a fiction? Pharm. Sci. Technol. Today. 1998, 1, 370-376.
4. Hamman, J.H.; Viljoen, A.M. Use of Aloe vera for increasing the bioavailability of poorly absorbable drugs. 2008. SA patent application 2008/01542.
5. Chen, W. Drug absorption enhancing properties of Aloe vera across the intestinal epithelium. D. Tech. Thesis, Tshwane University of Technology, South Africa, 2008.
6. Kulkarni, G.T.; Gowthamarajan, K.; Dhobe, R.R.; Yohanan, F.; Suresh, B. Development of controlled release spheroids using natural polysaccharide as release modifier. Drug Deliv. 2005,12, 201-206.
7. Aloe vera as a biologically active vehicle for hydrocortisone acetate.
8. Davis RH, Parker WL, Murdoch DP.
9. J Am Podiatr Med Assoc. 1991 Jan;81(1):1-9.