Design of cationic microspheres based on aminated gelatin for controlled release of peptide and protein drugs.
ABSTRACT Two different types of cationized microspheres based on a native cationic gelatin (NGMS) and aminated gelatin with ethylendiamine (CGMS) were investigated for the controlled release of three model acidic peptide/protein drugs with different molecular weights (MWs) and isoelectric points (IEPs). Recombinant human (rh)-insulin (MW: 5.8 kDa, IEP: 5.3), bovine milk lactoalbumin, BMLA (MW: 14 kDa, IEP: 4.3), and bovine serum albumin (BSA MW: 67 kDa, IEP: 4.9) were used as model acidic peptide/protein drugs. The in vitro release profiles of these acidic peptide/protein drugs from NGMS and CGMS were compared and different periods of cross-linking were obtained. The slower release of these acidic peptide/protein drugs from CGMS compared with those from NGMS with cross-linking for 48 hr. was caused by the suppression of burst release during the initial phase. The degree of suppression of burst release of the three peptide/protein drugs during the initial phase by CGMS was in the following order: (rh)-insulin > BMLA > BSA. The release of insulin with a lower molecular weight from CGMS was particularly suppressed compared with the other two drugs with higher molecular weights in the initial phase. The control of the release rate of acidic peptide/protein drugs from gelatin microsphere can be achieved by amination of gelatin. Therefore, CGMS is useful for the controlled release of acidic peptide/ protein drugs.
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ABSTRACT: This study demonstrates a facile but effective method to construct glucose coated magnetic Fe3O4 nanoparticles for drug delivery through a glycothermal method (100–200 °C). In this process, magnetic Fe3O4 nanoparticles were firstly prepared via a glycothermal reaction of Fe (III) salts (e.g., FeCl3·6H2O) in ethylene glycol. Second, the polymerized glucose was used as a carbon layer to coat on the surface of Fe3O4 nanoparticles. The polymerized glucose layer is biocompatible and can provide functional –OH groups for interaction with biomolecules that contain –COOH, –SH, and –NH2 groups. The particle characteristics (morphology, size, surface property) were identified by various techniques such as transmission electron microscopy (TEM), Fourier transform infrared (FT-IR) spectroscopy, and ultraviolet visible (UV–vis) spectrum. Finally, the polymerized-glucose coated magnetic Fe3O4 nanocomposites were used in drug delivery test at ambient conditions, and the loading or release performance of aspirin was assessed by using UV–vis spectroscopy. The influence of pH and ionic strength on the adsorption capacity has also been investigated. The findings in this study will be useful for engineering iron oxide nanoparticles for potential drug delivery applications.Powder Technology 02/2013; 236:157–163. DOI:10.1016/j.powtec.2012.03.008 · 2.27 Impact Factor
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ABSTRACT: The pharmacokinetic properties of a drug can be significantly improved by the delivery process. Scientists have understood that developing suitable drug delivery systems that release the therapeutically active molecule at the level and dose it is needed and during the optimal time represents a major advance in the field. Cell microencapsulation is an alternative approach for the sustained delivery of therapeutic agents. This technology is based on the immobilization of different types of cells within a polymeric matrix surrounded by a semipermeable membrane for the long-term release of therapeutics. As a result, encapsulated cells are isolated from the host immune system while allowing exchange of nutrients and waste and release of the therapeutic agents. The versatility of this approach has stimulated its use in the treatment of numerous medical diseases including diabetes, cancer, central nervous system diseases and endocrinological disorders among others. The aim of this review article is to give an overview on the current state of the art of the use of cell encapsulation technology as a controlled drug delivery system. The most important advantages of this type of "living" drug release strategy are highlighted, but also its limitations pointed out, and the major challenges to be addressed in the forthcoming years are described.Journal of Controlled Release 09/2008; 132(2):76-83. DOI:10.1016/j.jconrel.2008.08.010 · 7.26 Impact Factor
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ABSTRACT: An attempt was made to develop a new therapeutic delivery system which would play a dual role of attenuating MMP activity in the wounds and also prevent infection by controlled delivery of antimicrobials. A catechol type MMP inhibitor 2,3-dihydroxybenzoic acid (DHBA) was conjugated to gelatin microspheres using EDC/NHS as coupling agents. The potential of the modified gelatin microspheres (DHB-MS) to attenuate the proteases such as MMP 2 and MMP 9 in the diabetic wound tissues was investigated by gelatin zymography. Further the modified microspheres were loaded with doxycycline and impregnated in a reconstituted collagen scaffold as novel wound dressing. The in vitro release behavior of doxycycline from both DHB-MS and DHB-MS impregnated collagen scaffold was investigated. DHB-MS when incubated with the tissue lysate for 6h displayed the complete inhibition of the MMPs in the tissue lysate. The in vitro drug release studies from the collagen scaffold exhibited the burst release of 44%, exerted immediate chemo prophylaxis and sustained delivery for 72 h. The MTT assay and fluorescent labeling with calcein AM indicated that the DHB-MS is biocompatible to human foreskin fibroblasts. Thus the system developed provides wider scope to control the pathogens involved in infection and also the excess matrix degradation.European journal of pharmaceutical sciences: official journal of the European Federation for Pharmaceutical Sciences 11/2008; 36(2-3):235-45. DOI:10.1016/j.ejps.2008.09.010 · 3.01 Impact Factor