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Chitosan-genipin microspheres for the controlled release of drugs: clarithromycin, tramadol and heparin.

Harris R, Lecumberri E, Heras A - Mar Drugs (2010)

Bottom Line: Once the crosslinking process was characterized as a function of the factors mentioned above, drug loaded hydrochloride chitosan microspheres with different degrees of crosslinking were obtained.In conclusion, genipin showed to be eligible as a chemical-crosslinking agent delaying the outflow of drugs from the microspheres.However, more studies in vitro and in vivo must be carried out to determine adequate crosslinking conditions for different drugs.

View Article: PubMed Central - PubMed

Affiliation: Instituto de Estudios Biofuncionales, Departamento Química-Física II, Universidad Complutense Paseo Juan XXIII, Madrid, Spain. ruthharris@ieb.ucm.es

ABSTRACT
The aim of this study was to first evaluate whether the chitosan hydrochloride-genipin crosslinking reaction is influenced by factors such as time, and polymer/genipin concentration, and second, to develop crosslinked drug loaded microspheres to improve the control over drug release. Once the crosslinking process was characterized as a function of the factors mentioned above, drug loaded hydrochloride chitosan microspheres with different degrees of crosslinking were obtained. Microspheres were characterized in terms of size, morphology, drug content, surface charge and capacity to control in vitro drug release. Clarithromycin, tramadol hydrochloride, and low molecular weight heparin (LMWH) were used as model drugs. The obtained particles were spherical, positively charged, with a diameter of 1-10 microm. X-Ray diffraction showed that there was an interaction of genipin and each drug with chitosan in the microspheres. In relation to the release profiles, a higher degree of crosslinking led to more control of drug release in the case of clarithromycin and tramadol. For these drugs, optimal release profiles were obtained for microspheres crosslinked with 1 mM genipin at 50 °C for 5 h and with 5 mM genipin at 50 °C for 5 h, respectively. In LMWH microspheres, the best release profile corresponded to 0.5 mM genipin, 50 °C, 5 h. In conclusion, genipin showed to be eligible as a chemical-crosslinking agent delaying the outflow of drugs from the microspheres. However, more studies in vitro and in vivo must be carried out to determine adequate crosslinking conditions for different drugs.

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X-ray diffraction patterns of (a) tramadol hydrochloride and (b) chitosan hydrochloride (5 mg/mL) microspheres loaded with tramadol hydrochloride (30% w/w) and crosslinked with genipin (2 mM) at 50 ºC for 5 h.
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f5-marinedrugs-08-01750: X-ray diffraction patterns of (a) tramadol hydrochloride and (b) chitosan hydrochloride (5 mg/mL) microspheres loaded with tramadol hydrochloride (30% w/w) and crosslinked with genipin (2 mM) at 50 ºC for 5 h.

Mentions: The X-Ray diffraction patterns of genipin, chitosan hydrochloride, assayed drugs, and the combination of all microsphere components are shown in Figures 4–6. Genipin itself, as well as clarithromycin and tramadol hydrochloride, showed high crystallinity. On the other hand, the chitosan hydrochloride X-ray pattern showed its amorphous structure. Genipin, as well as clarithromycin (Figure 4) and tramadol hydrochloride (Figure 5) are included in the amorphous structure of chitosan when incorporated in microspheres. As can be seen in Figure 6, the LMWH X-ray pattern shows it as an amorphous compound. LMWH loaded microspheres crosslinked with genipin show an X-ray diffraction pattern with no marked peaks, which indicates that the crosslinking agent is molecularly dispersed in the polymer matrix [14,15], which should help to retard the delivery of the drug [16].


Chitosan-genipin microspheres for the controlled release of drugs: clarithromycin, tramadol and heparin.

Harris R, Lecumberri E, Heras A - Mar Drugs (2010)

X-ray diffraction patterns of (a) tramadol hydrochloride and (b) chitosan hydrochloride (5 mg/mL) microspheres loaded with tramadol hydrochloride (30% w/w) and crosslinked with genipin (2 mM) at 50 ºC for 5 h.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC2901822&req=5

f5-marinedrugs-08-01750: X-ray diffraction patterns of (a) tramadol hydrochloride and (b) chitosan hydrochloride (5 mg/mL) microspheres loaded with tramadol hydrochloride (30% w/w) and crosslinked with genipin (2 mM) at 50 ºC for 5 h.
Mentions: The X-Ray diffraction patterns of genipin, chitosan hydrochloride, assayed drugs, and the combination of all microsphere components are shown in Figures 4–6. Genipin itself, as well as clarithromycin and tramadol hydrochloride, showed high crystallinity. On the other hand, the chitosan hydrochloride X-ray pattern showed its amorphous structure. Genipin, as well as clarithromycin (Figure 4) and tramadol hydrochloride (Figure 5) are included in the amorphous structure of chitosan when incorporated in microspheres. As can be seen in Figure 6, the LMWH X-ray pattern shows it as an amorphous compound. LMWH loaded microspheres crosslinked with genipin show an X-ray diffraction pattern with no marked peaks, which indicates that the crosslinking agent is molecularly dispersed in the polymer matrix [14,15], which should help to retard the delivery of the drug [16].

Bottom Line: Once the crosslinking process was characterized as a function of the factors mentioned above, drug loaded hydrochloride chitosan microspheres with different degrees of crosslinking were obtained.In conclusion, genipin showed to be eligible as a chemical-crosslinking agent delaying the outflow of drugs from the microspheres.However, more studies in vitro and in vivo must be carried out to determine adequate crosslinking conditions for different drugs.

View Article: PubMed Central - PubMed

Affiliation: Instituto de Estudios Biofuncionales, Departamento Química-Física II, Universidad Complutense Paseo Juan XXIII, Madrid, Spain. ruthharris@ieb.ucm.es

ABSTRACT
The aim of this study was to first evaluate whether the chitosan hydrochloride-genipin crosslinking reaction is influenced by factors such as time, and polymer/genipin concentration, and second, to develop crosslinked drug loaded microspheres to improve the control over drug release. Once the crosslinking process was characterized as a function of the factors mentioned above, drug loaded hydrochloride chitosan microspheres with different degrees of crosslinking were obtained. Microspheres were characterized in terms of size, morphology, drug content, surface charge and capacity to control in vitro drug release. Clarithromycin, tramadol hydrochloride, and low molecular weight heparin (LMWH) were used as model drugs. The obtained particles were spherical, positively charged, with a diameter of 1-10 microm. X-Ray diffraction showed that there was an interaction of genipin and each drug with chitosan in the microspheres. In relation to the release profiles, a higher degree of crosslinking led to more control of drug release in the case of clarithromycin and tramadol. For these drugs, optimal release profiles were obtained for microspheres crosslinked with 1 mM genipin at 50 °C for 5 h and with 5 mM genipin at 50 °C for 5 h, respectively. In LMWH microspheres, the best release profile corresponded to 0.5 mM genipin, 50 °C, 5 h. In conclusion, genipin showed to be eligible as a chemical-crosslinking agent delaying the outflow of drugs from the microspheres. However, more studies in vitro and in vivo must be carried out to determine adequate crosslinking conditions for different drugs.

Show MeSH