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Original Article

Preparation and Evaluation of Once-a-day Injectable Microspheres of Interferon Alpha in Rats

, , , , &
Pages 449-461 | Received 16 Jul 1998, Accepted 28 Oct 1998, Published online: 26 Jun 2009
 

Abstract

Gelatin microspheres (ms) and gelatin/BSA (bovine serum albumin) or gelatin/alginate ms were prepared by encapsulating fluorescein isothiocyanate (FITC) labeled dextran or interferon alpha (IFN-α). Ms were obtained by an emulsion-solvent-extraction method. Gelatin and gelatin/BSA ms were obtained by treating water-in-oil (W/O) emulsions with iso-propyl alcohol. Gelatin/alginate ms having different composition (25/1,20/1,15/1,10/1 and 5/1) were obtained by treating a W/O emulsion composed of gelatin and sodium alginate with 0.5 M calcium chloride solution. The average diameters of all the prepared ms were approximately 300μm. The FITC-dextran loading efficiencies were 96.5 ± 0.6% for gelatin ms (#1), 97.3 ± 2.2% for gelatin/BSA ms (#2) and 68.7 ± 2.2%, 55.0 ± 3.9%, 47.5 ± 3.3%, 44.4 ± 1.2%, 27.1 ± 2.2% for gelatin/alginate ms (#3-#7). The IFN-α loading efficiencies were 10.8 ± 0.5% for gelatin/BSA ms (#8) and 22.5 ± 1.8%, 17.6 ± 0.9% and 14.5 ± 0.5% for gelatin/alginate ms (#9, #10 and #11). In vitro release studies with ms containing FITC-dextran showed that the release rate of FITC-dextran from the ms decreased by the modification of gelatin ms with BSA or sodium alginate, although the effect of BSA addition to gelatin ms did not elucidate satisfactory sustained-release characteristics of FITC-dextran after subcutaneous (sc) injection to rats. By decreasing the formulated ratio of gelatin/alginate from 25/1 to 5/1, the mean T50%, the time when the half amount of FITC-dextran contained was released from the ms, increased from 1.7 ± 0.1 to 13.8 ± 3.6 h and three ms preparations (#4, #5 and #6) showed sustained-release characteristics on the serum FITC-dextran concentration-time profiles. Based on these results, three types of ms containing IFN-α were prepared and in vivo pharmacokinetic studies were performed in rats, where the dose of IFN-α was 2 ± 104 IU/rat. By the addition of alginate to gelatin, the release rate of IFN-α was decreased and the serum IFN-α concentration-time profiles showed better sustained-release characteristics of IFN-α from #10 ms than the other IFN-α ms (#8, #9 and #11) after sc injection to rats.

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