Formulation and characterization of gentamicin-loaded albumin microspheres as a potential drug carrier for the treatment of E. coli K88 infections
Keywords:
Gentamicin, glutaraldehyde cross-linking albumin microspheres, antibacterial activityAbstract
Ion exchange resins are commonly used for masking of drug objectionable taste. Our work aimed to study the effect of this complexation on the drug stability and bioavailability in rabbits. In this work, paracetamol and ibuprofen complexes with indion 204 were prepared; drug stability and bioavailability from the prepared complexes were studied and compared with that of the commonly used commercial tablets Tylenol and Motrin respectively. The clinical protocol and information about drugs were discussed with a group of healthy albino rabbits. The results showed that tmax of both drugs were kept constant at 1.5hrs and 2hrs without any change from the reference standards Tylenol and Motrin respectively. The calculated pharmacokinetic parameters Cpmax, AUC(0-24) and AUC(0-∞) respectively for paracetamol were 0.431µg/ml, 3.535µg.hr/ml and 3.756µg.hr/ml from the prepared complexes in comparison to 0.494µg/ml, 4.083µg.hr/ml, 4.198µg.hr/ml from Tylenol, and 0.743µg/ml, 5.380µg.hr/ml, 5.559µg.hr/ml from the prepared ibuprofen complexes in comparison to 0.803µg/ml, 6.272 µg.hr/ml, 6.432 µg.hr/ml from Motrin. The relative bioavailability of both drugs from the prepared complexes were calculated using Tylenol and Motrin as reference standards and the 90 % confidence intervals of the geometric mean values for the test/reference ratios for Cpmax, AUC (0-24) and AUC (0-∞) were within the bioequivalence acceptance range of 80–125 % according to the European Guideline. Statistical analysis (ANOVA) indicated a significance difference between the calculated pharmacokinetic parameters for both drugs. From these results we can conclude that indion complexation of drugs significantly affects their pharmacokinetics and retards their bioavailability.
References
. 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.
