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Title: Development of formaldehyde-free agar/gelatin microcapsules containing berberine HCl and gallic acid and their topical and oral applications
Authors: Lam, PL
Lee, KKH
Kok, SHL
Cheng, GYM
Tao, XM 
Hau, DKP
Yuen, MCW
Lam, KH
Gambari, R
Chui, CH
Wong, RSM
Issue Date: 2012
Source: Soft matter, 2012, v. 8, no. 18, p. 5027-5037
Abstract: The safety issues of biomedical applications have been a major concern in recent years. Drug delivery associated with microencapsulation technology has been focused on as microencapsulated drugs are believed to promote comparative therapeutic efficiency on human absorption and prolong the life cycle of drugs. The most commonly applied crosslinker is formaldehyde in a gelatin microencapsulation system, which is considerably toxic to the human body. To reduce the risks involved when using formaldehyde, agar was associated with gelatin as the wall matrix materials of microcapsules as it could crosslink with gelatin to give a gel network in the microcapsules formation. Here we report the development, characterization and safe use of agar-gelatin microcapsules. We further demonstrate that both oral and topical applications are possible using the berberine HCl and gallic acid loaded microcapsules respectively. Microcapsules containing both drugs were prepared combining the optimal parameters identified. The mean drug loading efficiency and the mean particle sizes of the berberine HCl loaded microcapsules were 78.16% and 16.75 μm respectively, while those of gallic acid loaded microcapsules were 70.28% and 21.98 μm respectively. The compositions and surface morphology of berberine HCl and gallic acid containing microcapsules were examined using Fourier transform infrared (FTIR) spectroscopy and scanning electron microscopy (SEM). The in vitro controlled release models demonstrated that the drugs could be gradually released from the microcapsules. The minimum inhibitory concentrations (MICs) and anti-Staphylococcus aureus activity also proved that the berberine HCl loaded microcapsules exhibited better antibacterial activity towards Staphylococcus aureus when compared with those of the original drugs. The in vitro drug delivery model also demonstrated the delivery of berberine HCl from microcapsule treated textiles into nude mice skin. The in vivo mice disease model also showed that gallic acid loaded microcapsules were helpful in the treatment of acute liver and kidney toxicity after an overdose administration of acetaminophen. The development of agar-gelatin microcapsules was demonstrated to be an efficient, deliverable tool for both oral and topical applications.
Journal: Soft Matter 
ISSN: 1744-683X
DOI: 10.1039/c2sm07236j
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