Purpose: The fate of drug nanocarriers (NCs) in the inner ear remains elusive. The aim of the work is to develop ferrocene (FER)-loaded NCs to elucidate the cochlear biodistribution of such NCs. Methods: FER-NCs were prepared by surfactant free solvent-diffusion technique using a mixture of PLGA/PCL-PEG (ratios 1/1, 1/2) dissolved in acetone. FER-NCs were washed and freeze-dried. TEM analyses were carried out to study the FER-NC morphology. Lactose, mannitol, sucrose were tested at different cryoprotectant/nanocarrier ratios (0/1, 1/1, 3/1, 5/1) to stabilize FER-NCs during freeze-drying. The stability of the FER-NCs was checked by measuring particle size and zeta potential (ZP) immediately after water dispersion and after 12 days. FER-NCs were placed in the round window (RW) niche of the middle ear in guinea pigs. After 48 hours, the animals were sacrificed, the cochlea isolated and prepared for TEM. Results: The Ferrocene-loaded NCs had a mean diameter of 201.2±57.7, PDI of 0.328±0.074 and ZP of -20.2±4.8mV. PLGA/PCLPEG NCs of 1/2 allowed higher EE% (85.50±11.15) than ones made with 1/1 ratio (42.93±3.65). The FER-NCs appeared spherical with smooth surface. All cryoprotectants increased RES-NCs stability during the freeze-drying process. However, lactose, especially when used in 3/1 ratio, was more effective than other ones after dispersion and during 12-day stability studies. FER-NCs crossed the RW membrane and were found adjacent or in the cells lining the scala tympani of the cochlea. Hearing was normal after RW placement of NCs. Conclusion: FER-NCs were successfully prepared by emulsion-diffusion technique and the 1/2 PLGA/PLC-PEG ratio was selected in term of best encapsulation efficiency. Moreover, lactose (3/1 cryoprotectant/NCs ratio) guaranteed FER-NCs stability during freeze-drying process and maintained FER-NCs stable in suspension for at least 12 days. When placed into the RW niche, FER-NCs enter the cochlea and do not appear to cause hearing loss.
Ferrocene-loaded nanocarrier as probe for cochlear biodistribution study / U. Musazzi, I. Youm, M.A. Gratton, B.B.C. Youan. - In: THE AAPS JOURNAL. - ISSN 1550-7416. - (2013 Nov 10), pp. 1-1. ((Intervento presentato al convegno AAPS Annual Meeting and Exposition tenutosi a San Antonio nel 2013.
Ferrocene-loaded nanocarrier as probe for cochlear biodistribution study
U. MusazziPrimo
;
2013
Abstract
Purpose: The fate of drug nanocarriers (NCs) in the inner ear remains elusive. The aim of the work is to develop ferrocene (FER)-loaded NCs to elucidate the cochlear biodistribution of such NCs. Methods: FER-NCs were prepared by surfactant free solvent-diffusion technique using a mixture of PLGA/PCL-PEG (ratios 1/1, 1/2) dissolved in acetone. FER-NCs were washed and freeze-dried. TEM analyses were carried out to study the FER-NC morphology. Lactose, mannitol, sucrose were tested at different cryoprotectant/nanocarrier ratios (0/1, 1/1, 3/1, 5/1) to stabilize FER-NCs during freeze-drying. The stability of the FER-NCs was checked by measuring particle size and zeta potential (ZP) immediately after water dispersion and after 12 days. FER-NCs were placed in the round window (RW) niche of the middle ear in guinea pigs. After 48 hours, the animals were sacrificed, the cochlea isolated and prepared for TEM. Results: The Ferrocene-loaded NCs had a mean diameter of 201.2±57.7, PDI of 0.328±0.074 and ZP of -20.2±4.8mV. PLGA/PCLPEG NCs of 1/2 allowed higher EE% (85.50±11.15) than ones made with 1/1 ratio (42.93±3.65). The FER-NCs appeared spherical with smooth surface. All cryoprotectants increased RES-NCs stability during the freeze-drying process. However, lactose, especially when used in 3/1 ratio, was more effective than other ones after dispersion and during 12-day stability studies. FER-NCs crossed the RW membrane and were found adjacent or in the cells lining the scala tympani of the cochlea. Hearing was normal after RW placement of NCs. Conclusion: FER-NCs were successfully prepared by emulsion-diffusion technique and the 1/2 PLGA/PLC-PEG ratio was selected in term of best encapsulation efficiency. Moreover, lactose (3/1 cryoprotectant/NCs ratio) guaranteed FER-NCs stability during freeze-drying process and maintained FER-NCs stable in suspension for at least 12 days. When placed into the RW niche, FER-NCs enter the cochlea and do not appear to cause hearing loss.
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