Enhanced Oral Bioavailability of Poorly Absorbed Drugs. I. Screening of Absorption Carrier for the Ceftriaxone Complex

Cho, Seong-Wan; Lee, Jeoung Soo; Choi, Sun‐Woo

doi:10.1002/jps.10563

Cited by 37 publications

(27 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The mobile phase was a mixture of phosphate buffer (10 mM, pH 7) and acetonitrile (0.64% tetrabutyl ammonium bromide) (50:50, v/ v), which was delivered through the column at a flow rate of 1 mL/min. 17 …”

Section: Intra-duodenal Administration Of Ceftriaxone/dcea Formulationmentioning

confidence: 97%

Cationic Analog of Deoxycholate as an Oral Delivery Carrier for Ceftriaxone

Lee

Kim

Lee

et al. 2005

Journal of Pharmaceutical Sciences

View full text Add to dashboard Cite

Section: Intra-duodenal Administration Of Ceftriaxone/dcea Formulationmentioning

confidence: 97%

Cationic Analog of Deoxycholate as an Oral Delivery Carrier for Ceftriaxone

Lee

Kim

Lee

et al. 2005

Journal of Pharmaceutical Sciences

View full text Add to dashboard Cite

“…Another aimed at using absorption enhancers for increasing its membrane permeability (18). One strategy to improve cellular access is to incorporate the antibiotic into a nanoparticulate system that would be ingested by phagocytic cells of the mononuclear phagocytic system (MPS), (19)(20)(21).…”

Section: Introductionmentioning

confidence: 99%

Enhanced Antibacterial Effect of Ceftriaxone Sodium-Loaded Chitosan Nanoparticles Against Intracellular Salmonella typhimurium

2012

View full text Add to dashboard Cite

Abstract. The aim of the present study was to utilize chitosan (CS) nanoparticles for the intracellular delivery of the poorly cell-penetrating antibiotic, ceftriaxone sodium (CTX). In vitro characterization of (CTX-CS) nanoparticles was conducted leading to an optimized formula that was assessed for its biocompatibility to blood (hemolysis test) and cells (MTT assay). Progressively, confocal laser scanning microscopy (CLSM), cellular uptake (microfluorimetry), and antibacterial activity of the nanoparticles were investigated in two cell lines: Caco-2 and macrophages J774.2 pre-infected with Salmonella typhimurium. Results showed that the optimized formula had size 210 nm, positive zeta potential (+30 mV) and appreciable entrapment efficiency for CTX (45%) and included a biphasic release pattern. The nanoparticles were biocompatible and were internalized by cells as verified by CLSM whereas microfluorimetry indicated substantial cellular uptake. Moreover, the CTX-chitosan nanoparticles showed a significant reduction in the count of intracellular S. typhimurium in Caco-2 and macrophages J774.2. This reduction was significantly higher than that obtained in case of placebo nanoparticles, CTX, and CTX-chitosan solutions and might be attributed to enhanced endocytic uptake of the nanoaprticles and antibacterial effect of the chitosan polymer. In conclusion, the results provide evidence for the potential use of chitosan nanoparticles to enhance the intracellular delivery and antibacterial effect of CTX in enterocytes and macrophages.

show abstract

“…CRO concentrations were analyzed on a reversed-phase high-performance liquid chromatograph (RP-HPLC) (Shimadzu, Tokyo, Japan) as previously described (3). Briefly, a 50-l aliquot of supernatant was injected into an RP-HPLC fitted with an Eclipse XDB analytical column (25-cm by 4.5-cm inside diameter; Agilent, Palo Alto, CA).…”

mentioning

confidence: 99%

Pharmacokinetics of a New, Orally Available Ceftriaxone Formulation in Physical Complexation with a Cationic Analogue of Bile Acid in Rats

Lee

Kim

Lee

et al. 2006

Antimicrob Agents Chemother

View full text Add to dashboard Cite

Oral administration of ceftriaxone associated with a bile acid-based new oral carrier, cholylethylenediamine, in 50% propylene glycol to rats at doses of 25 and 50 mg/kg of body weight resulted in a significant increase in intestinal absorption, as evidenced by 55% improvement in the bioavailability, whereas ceftriaxone alone showed a bioavailability of less than 1%.The introduction of new oral cephalosporins, or formulation development of existing and highly promising parenteral cephalosporins, provides a possibility for follow-up oral treatment after initial parenteral treatment, thus reducing hospitalization time and costs (5,6,14). Ceftriaxone (CRO) is a widely used injectable broad-spectrum cephalosporin that exhibits potent activity against gram-positive and gram-negative bacteria (1, 2, 11, 12). However, the therapeutic utility of ceftriaxone is limited, as it requires parenteral infusion for its administration. In this respect, the development of an oral formulation of CRO would be helpful in rapid and proper step-down therapy that would lead to better patient compliance without compromising the therapeutic activity.In a previous study, we developed a new oral delivery carrier based on bile acids, which could improve the oral bioavailability of therapeutically active peptides without damaging the tissue structure of the mucous membrane (8, 9). Based on the observation that associated bile acid could increase the absorption of a poorly absorbable drug in the intestine, we prepared a positively charged carrier by simple modification of bile acid, cholic acid, with ethylenediamine for the negatively charged small organic molecules, CRO. This scheme was designed with the goal of preparing a carrier that could physically associate with the drug by ion pair interaction to improve its lipophilicity without altering the structure of the native drug. In the present study, we show that the positively charged bile acid analogue forms a complex with CRO and report the impact of this association on the oral bioavailability.Cholylethylendiamine (CEA) was synthesized by using cholic acid and ethylenediamine as precursors. A delivery agent was composed of the hydrophobic part of bile acid and the positive charge of ethylenediamine, thereby facilitating an ionpairing interaction with anionic drug, CRO. The complex formation in aqueous medium was reversible and dependent on the molar ratio between CRO and the delivery agent. Since CRO/CEA complexes showed significantly reduced solubility in water, the lyophilized drug complex was reformulated by the addition of one of the most common water-soluble solvents, propylene glycol (PG) (15), as a prototype formulation.The partition coefficients of CRO/CEA complexes were investigated in an n-octanol/water system. CRO concentrations were analyzed on a reversed-phase high-performance liquid chromatograph (RP-HPLC) (Shimadzu, Tokyo, Japan) as previously described (3). Briefly, a 50-l aliquot of supernatant was injected into an RP-HPLC fitted with an Eclipse XDB analytical column (25...

show abstract

Enhanced Oral Bioavailability of Poorly Absorbed Drugs. I. Screening of Absorption Carrier for the Ceftriaxone Complex

Cited by 37 publications

References 23 publications

Cationic Analog of Deoxycholate as an Oral Delivery Carrier for Ceftriaxone

Cationic Analog of Deoxycholate as an Oral Delivery Carrier for Ceftriaxone

Enhanced Antibacterial Effect of Ceftriaxone Sodium-Loaded Chitosan Nanoparticles Against Intracellular Salmonella typhimurium

Pharmacokinetics of a New, Orally Available Ceftriaxone Formulation in Physical Complexation with a Cationic Analogue of Bile Acid in Rats

Contact Info

Product

Resources

About