Effect of types of solid lipids on the physicochemical properties and self-aggregation of amphotericin B loaded nanostructured lipid carriers(NLCs)

,Wree Tiyoonchi,*, Supporn Lmlertthon

aFaculty of Pharmaceutical Sciences,Naresuan University,Phitsanulok 65000,Thailand

bFaculty of Medical Sciences,Naresuan University,Phitsanulok 65000,Thailand

Effect of types of solid lipids on the physicochemical properties and self-aggregation of amphotericin B loaded nanostructured lipid carriers(NLCs)

Pataranapa Nimtrakula,Waree Tiyaboonchaia,*, Supaporn Lamlertthonb

aFaculty of Pharmaceutical Sciences,Naresuan University,Phitsanulok 65000,Thailand

bFaculty of Medical Sciences,Naresuan University,Phitsanulok 65000,Thailand

A R T I C L E I N F O

Article history:

Available online 25 November 2015

Nanostructure lipid carriers

Amphotericin B

Oral administration

Solid lipid

Self-aggregation

Amphotericin B(AmB),a polyene antibiotic,is one of the gold standards for the treatment of systemic fungal infections and leishmaniasis.Nowadays,only intravenous administration of AmB has been available;because AmB is poorly absorbed from the gastrointestinal(GI)tract due to its low aqueous solubility.Currently,2 forms ofAmB are available.The frst is a mixture of AmB and sodium deoxycholate(Fungizone®)that produces severe nephrotoxicity,which may lead to kidney failure. The second is lipid-based formulations that are found to reduce nephrotoxicity,but these products are costly and require higher dose than Fungizone®[1–3].Thus,the cheaper delivery system with reduced AmB toxicity is needed.

In this study,we attempted to developed AmB-loaded nanostructure lipid carriers(NLCs)prepared by high pressure homogenization technique(HPH).The AmB-loaded NLCs could be successfully developed.The mean particle size was affected by the types of solid lipids.AmB-loaded NLCs prepared with stearic acid(S),palmitic acid(P)and myristic acid(M)possessed mean particle size of 141.57,129.90 and 113.40 nm, respectively,All formulation showed a narrow size distribution with a polydispersity index of～0.3 and zeta potential value of～−20 mV.The high incorporation effciency of AmB,～80%, was achieved.The UV–vis spectroscopy was used to investigate the aggregation state of AmB associated to NLCs.The electronic absorbance spectrum of AmB in 50%(v/v)methanol,representing the monomeric form,showed a peak ratio (326/418)of 0.07,while Fungizone®,which represented the selfaggregation state of AmB,showed the peak ratio(326/418)of 2.45.The results revealed that AmB-loaded NLCs showed less aggregation state of AmB than Fungizone®.The peak ratio of AmB-loaded NLCs in formulations S,P,and M was 1.29,1.41, and 1.80,respectively,suggesting partially aggregation state. Aggregation form of AmB-loaded NLCs was found to be dependent on the types of solid lipids;a long chain solid lipidtended to decrease the aggregation form.These results suggested that AmB-loaded NLCs could offer a reduction in nephrotoxicity compared to Fungizone®.

Fig.1–Physicochemical properties and self-aggregation state of AmB-loaded NLCs.PI=polydispersity index;BI=baseline index.

Acknowledgements

The authors acknowledged the fnancial support from Naresuan University,Phitsanulok,Thailand.

R E F E R E N C E S

[1]Deray G.Amphotericin B nephrotoxicity.J Antimicrob Chemother 2002;49:37–41.

[2]Hamill RJ.Amphotericin B formulations:a comparative review of effcacy and toxicity.Drugs 2013;73:919–934.

[3]Laniado-Laborin R,Cabrales-Vargas MN.Amphotericin B:side effects and toxicity.Rev Iberoam Micol 2009;26(4):223–227.

*E-mail address:wareet@nu.ac.th.

Peer review under responsibility of Shenyang Pharmaceutical University.

http://dx.doi.org/10.1016/j.ajps.2015.11.054

1818-0876/©2016 Production and hosting by Elsevier B.V.on behalf of Shenyang Pharmaceutical University.This is an open access article under the CC BY-NC-ND license(http://creativecommons.org/licenses/by-nc-nd/4.0/).