Formulation and characterization of gentamicin-loaded albumin microspheres as a potential drug carrier for the treatment of E. coli K88 infections

ANDREI SARABIA-SAINZ, Gabriela Ramos-Clamont Montfort, Jaime Lizardi-Mendoza, María Del Pilar Sánchez-Saavedra, María Del Carmen Candia-Plata, Roberto Z. Guzman, Armando Lucero-Acuña, Luz Vazquez-Moreno


The aim of this study was to formulate and characterize gentamicin-loaded albumin microspheres for their potential therapeutic use in E. coli K88 infections. Based on in vitro assays, it is proposed that microspheres may serve as a carrier of gentamicin and may provide localized antibacterial activity in the treatment of porcine colibacillosis. Gentamicin-albumin microspheres (GAM) were obtained using a water/oil (W/O) emulsion followed by cross-linking with different concentrations of glutaraldehyde. Electron microscopy showed spherical particles with indentations. The average size of the GAM was 10.5-12.3 µm. At pH 7.2, the release kinetics of gentamicin from the GAM was successfully described as an initial burst defined by a first order equation.  Gentamicin release was unaffected by the glutaraldehyde concentrations used but was affected by acidic conditions.  The behavior of gentamicin release from the GAM was not altered by digestion with trypsin and chymotrypsin at pH 7.2. Additionally, the concentration of gentamicin released from GAM to reach antibacterial activity was similar to that of free gentamicin against E. coli K88. This work shows the potential use of GAM as therapeutic vehicles of gentamicin to counteract intestinal infections in pigs


Gentamicin; glutaraldehyde cross-linking albumin microspheres; antibacterial activity

Full Text:



. Fairbrother JM, Nadeau É, and Gyles CL, Escherichia coli in postweaning diarrhea in pigs: an update on bacterial types, pathogenesis, and prevention strategies. Animal Health Research Reviews, 2005. 6(1): p. 17-40.

. Francis DH, Erickson AK, and Grange PA, K88 adhesins of enterotoxigenic Escherichia coli and their porcine enterocyte receptors. Advances in experimental medicine and biology, 1999. 473: p. 147.

. Grange PA, Erickson AK, Anderson TJ, and Francis DH, Characterization of the carbohydrate moiety of intestinal mucin-type sialoglycoprotein receptors for the K88ac fimbrial adhesin of Escherichia coli. Infection and immunity, 1998. 66(4): p. 1613-1621.

. Barton MD, Antibiotic use in animal feed and its impact on human health. Nutrition Research Reviews, 2000. 13(2): p. 279-300.

. Radostits O, Gay C, Blood D, Hinchcliff K, and Arundel J, Veterinary medicine: a textbook of the diseases of cattle, sheep, goats, pigs and horses. WB Saunders Company Ltd, London, 2000. 9: p. 867-882.

. Lloyd K, Stover S, Pascoe J, and Adams P, Synovial fluid pH, cytologic characteristics, and gentamicin concentration after intra-articular administration of the drug in an experimental model of infectious arthritis in horses. American journal of veterinary research, 1990. 51(9): p. 1363.

. Hanssen AD, Local antibiotic delivery vehicles in the treatment of musculoskeletal infection. Clinical orthopaedics and related research, 2005. 437: p. 91.

. DuPont HL, Treatment of travelers’ diarrhea. Journal of travel medicine, 2001. 8: p. s31-s33.

. Amezcua R, Friendship RM, Dewey CE, Gyles C, and Fairbrother JM, Presentation of postweaning Escherichia coli diarrhea in southern Ontario, prevalence of hemolytic E. coli serogroups involved, and their antimicrobial resistance patterns. Canadian journal of veterinary research, 2002. 66(2): p. 73.

. FDA, Code of Federal Regulations-Title 21. Gentamicin Sulfate Soluble Powder. 21CFR 520.1044c. 21.

. Bhatnagar S, Bhan MK, Sazawal S, Gupta U, George C, Arora NK, and Kashyap DK, Efficacy of massive dose oral gentamicin therapy in nonbloody persistent diarrhea with associated malnutrition. J Pediatr Gastroenterol Nutr 1992. 15(2): p. 117-124.

. Islam M, Alam A, Hossain M, Mahalanabis D, and Hye H, Double-blind comparison of oral gentamicin and nalidixic acid in the treatment of acute shigellosis in children. Journal of tropical pediatrics, 1994. 40(6): p. 320-325.

. Maxwell L, Shepherd A, Riedel G, and Morris M, Effect of microsphere size on apparent intramural distribution of intestinal blood flow. American Journal of Physiology-Heart and Circulatory Physiology, 1981. 241(3): p. H408-H414.

. Damge C, Aprahamian M, Marchais H, Benoit J, and Pinget M, Intestinal absorption of PLAGA microspheres in the rat. Journal of anatomy, 1996. 189(Pt 3): p. 491.

. Tabassi SAS and Razavi N, Preparation and characterization of albumin microspheres encapsulated with propranolol HCl. DARU Journal of Pharmaceutical Sciences, 2003. 11(4).

. Mathew ST, Devi SG, and Sandhya K, Formulation and evaluation of ketorolac tromethamine-loaded albumin microspheres for potential intramuscular administration. AAPS PharmSciTech, 2007. 8(1): p. 100-108.

. Zhang C, Cheng Y, Qu G, Wu X, Ding Y, Cheng Z, Yu L, and Ping Q, Preparation and characterization of galactosylated chitosan coated BSA microspheres containing 5-fluorouracil. Carbohydrate Polymers, 2008. 72(3): p. 390-397.

. Matkovic S, Valle G, and Briand L, Quantitative analysis of ibuprofen in pharmaceutical formulations through FTIR spectroscopy. Latin American applied research, 2005. 35(3): p. 189-195.

. Bunaciu AA, Aboul-Enein HY, and Fleschin Ş, FT-IR Spectrophotometric analysis of acetylsalicylic acid and its pharmaceutical formulations. Canadian journal of analy. Sci. and spectrosc, 2006. 51: p. 253-259.

. Haswani DK, Nettey H, Oettinger C, and D'Souza MJ, Formulation, characterization and pharmacokinetic evaluation of gentamicin sulphate loaded albumin microspheres. Journal of microencapsulation, 2006. 23(8): p. 875-886.

. Prior S, Gander B, Lecároz C, Irache JM, and Gamazo C, Gentamicin-loaded microspheres for reducing the intracellular Brucella abortus load in infected monocytes. Journal of Antimicrobial Chemotherapy, 2004. 53(6): p. 981-988.

. Fayle SE, Healy JP, Brown PA, Reid EA, Gerrard JA, and Ames JM, Novel approaches to the analysis of the Maillard reaction of proteins. Electrophoresis, 2001. 22(8): p. 1518-1525.

. Jensen MS, Jensen SK, and Jakobsen K, Development of digestive enzymes in pigs with emphasis on lipolytic activity in the stomach and pancreas. Journal of animal science, 1997. 75(2): p. 437-445.

. Korsmeyer RW, Gurny R, Doelker E, Buri P, and Peppas NA, Mechanisms of solute release from porous hydrophilic polymers. International journal of Pharmaceutics, 1983. 15(1): p. 25-35.

. Ritger PL and Peppas NA, A simple equation for description of solute release I. Fickian and non-Fickian release from non-swellable devices in the form of slabs, spheres, cylinders or discs. Journal of controlled release, 1987. 5(1): p. 23-36.

. Lao LL, Peppas NA, Boey FYC, and Venkatraman SS, Modeling of drug release from bulk-degrading polymers. International journal of Pharmaceutics, 2011. 418(1): p. 28-41.

. Costa P and Sousa Lobo JM, Modeling and comparison of dissolution profiles. European journal of pharmaceutical sciences, 2001. 13(2): p. 123-133.

. Egbaria K and Friedman M, Sustained in vitro activity of human albumin microspheres containing chlorhexidine dihydrochloride against bacteria from cultures of organisms that cause urinary tract infections. Antimicrobial agents and chemotherapy, 1990. 34(11): p. 2118-2121.

. Wang M, Coffer JL, Dorraj K, Hartman PS, Loni A, and Canham L, Sustained antibacterial activity from triclosan-loaded nanostructured mesoporous silicon. Molecular Pharmaceutics, 2010.

. Bahukudumbi P, Carson K, Rice-Ficht A, and Andrews M, On the diameter and size distributions of bovine serum albumin (BSA)-based microspheres. Journal of microencapsulation, 2004. 21(7): p. 787-803.

. Grange PA, Mouricout MA, Levery SB, Francis DH, and Erickson AK, Evaluation of receptor binding specificity of Escherichia coli K88 (F4) fimbrial adhesin variants using porcine serum transferrin and glycosphingolipids as model receptors. Infection and immunity, 2002. 70(5): p. 2336-2343.

. Leo E, Angela Vandelli M, Cameroni R, and Forni F, Doxorubicin-loaded gelatin nanoparticles stabilized by glutaraldehyde: Involvement of the drug in the cross-linking process. International journal of Pharmaceutics, 1997. 155(1): p. 75-82.

. Katti D, Preparation of albumin microspheres by an improved process. Journal of microencapsulation, 1999. 16(2): p. 231-242.

. Nettey H, Haswani D, Oettinger CW, and D'Souza MJ, Formulation and testing of vancomycin loaded albumin microspheres prepared by spray-drying. Journal of microencapsulation, 2006. 23(6): p. 632-642.

. Petroski D, Endoscopic comparison of various aspirin preparations. Gastric mucosal adaptability to aspirin restudied. Current Therapeutic Research, Clinical and Experimental, 1989. 45(6): p. 945-954.

. Cole ET, Scott RA, Connor AL, Wilding IR, Petereit HU, Schminke C, Beckert T, and Cadé D, Enteric coated HPMC capsules designed to achieve intestinal targeting. International journal of Pharmaceutics, 2002. 231(1): p. 83-95.

. Theodorou V, Fioramonti J, Hachet T, and Bueno L, Absorptive and motor components of the antidiarrhoeal action of loperamide: an in vivo study in pigs. Gut, 1991. 32(11): p. 1355-1359.

. Stubbings W, Bostock J, Ingham E, and Chopra I, Mechanisms of the post-antibiotic effects induced by rifampicin and gentamicin in Escherichia coli. Journal of Antimicrobial Chemotherapy, 2006. 58(2): p. 444-448.


  • There are currently no refbacks.

Copyright (c)

               AR Journals

18K, Street 1st, Gaytri Vihar, Pinto Park, Gwalior, M.P. India (Design) 2009-2021


Follow @arjournals on Twitter