J Korean Med Sci.  2005 Apr;20(2):297-301. 10.3346/jkms.2005.20.2.297.

Biodegradable Polymer Releasing Antibiotic Developed for Drainage Catheter of Cerebrospinal Fluid:In Vitro Results

• Han SY
• Yoon SH
• Cho KH
• Cho HJ
• An JH
• Ra YS

• KMID: 1095207
• DOI: http://doi.org/10.3346/jkms.2005.20.2.297

Abstract

The authors developed a biodegradable polymer that releases an antibiotic (nalidixic acid) slowly and continuously, for prevention of catheter-induced infection during drainage of cerebrospinal fluid. We investigated the in vitro antibiotic releasing characteristics and bacterial killing effects of the new polymer against E. coli. The novel fluoroquinolone polymer was prepared using diisopropylcarbodiimide, poly (e-capro-lactone) diol, and nalidixic acid. FT-IR, mass spectrometry, and elemental analysis proved that the novel antibacterial polymer was prepared successfully without any side products. Negative MS showed that the released drug has a similar molecular weight (M.W.=232, 350) to pure drug (M.W.=232). In high pressure liquid chromatography, the released drug and drug-oligomer showed similar retention times (about 4.5-5 min) in comparison to pure drug (4.5 min). The released nalidixic acid and nalidixic acid derivatives have antibacterial characteristics against E. Coli, Staphylococcus aureus, and Salmonella typhi, of more than 3 months duration. This study suggests the possibility of applying this new polymer to manufacture drainage catheters that resist catheter-induced infection, by delivering antibiotics for a longer period of more than 1 month.

Keyword

Anti-Bacterial Agents; Polymers; Drug Carriers; Catheters, Indwelling; Cerebrospinal Fluid; Drainage

MeSH Terms

Anti-Bacterial Agents/*administration & dosage
Biodegradation
Biofilms
Catheterization/*adverse effects
Cerebrospinal Fluid/*physiology
Chromatography, High Pressure Liquid
Drainage/*adverse effects
*Drug Delivery Systems
Humans
Nalidixic Acid/*administration & dosage
Polymers/administration & dosage
Research Support, Non-U.S. Gov't
Spectrum Analysis, Mass

Figure

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  Fig. 1 Construction of new antibiotic polymer and its action mechanism.

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  Fig. 2 Synthesis and 3 dimension structure of nalidixic-polymer from nalidixic acid and poly (caprolactone) diol.

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  Fig. 3 Mass spectrometric analysis of the released drug. (A) control of nalidixic acid, (B) control of polymer, (C) nalidixic polymer at 0 day in PBS buffer, (D) after 1 weeks in PBS buffer, (E) after 3 weeks in PBS buffer, (F) after 6 weeks in PBS buffer. Two major peaks in (D), (E), and (F) are correspond to the pure drug, nalidixic acid and nalidixic acid salt which are the major products of degradation and release. Minor peaks in (C), (D), (E), and (F) might be the degraded products of the drug bounded oligomer in which the cleavage sites are other than the ester linkage directly attatched

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  Fig. 4 Analysis with High Pressure Liquid Chromatography for polymer, nalidixic acid, nalidixic acid polymer in chloroform and nalidixic acid polymer after 7 days in PBS buffer pH 7.4.

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  Fig. 5 Cumulative drug release from the drug polymer. Drugs are bounded to poly(caprolactone)[M.W.=1250] and 20 mg of drug bounded PCL are mixed with 10 g of poly (caprolactone) [M.W.= 42,500]. Released drug % is based on the initial loaded pure drug.

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  Fig. 6 Cummulative in vitro antibacterial activity test against E. coli, S. aureus, and S. typhi that is calculated relatively from the zone of inhibition in agar plate culture of 10 µL of PBS immersed of nalidixic acid polymer for 5-30 days.

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