**1. Introduction**

146 Polyurethane

5,pp. 1682-1688.

966-969.

stents.J. Endourol. Vol. 7, No 2,pp. 105-115.

Intern. Med. Vol. 127, No 4,pp. 267-274.

heparin.J. Urol. Vol. 138, pp. 423-426.

No 3,pp. 199-213.

67-90.

Lingeman, J. E., et al. (2003). Use of a temporary ureteral drainage stent (TUDS) after uncomplicated ureteroscopy: results from a phase II clinical trial.J. Urol. Vol. 169, No

Mardis, H. K., et al. (1993). Comparative evaluation of materials used for internal ureteral

Multanen, M., et al. (2000). Bacterial adherence to ofloxacin-blended poly-lactone-coated self-reinforced L-lactic acid polymer urological stents.BJU International Vol. 86, No,pp.

Olweny, E. O., et al. (2002). Evaluation of the use of a biodegradable ureteric stent after retrograde endopyelotomy in a porcine model.J. Urol. Vol. 167, No 5,pp. 2198-2202. Piper, J. (1946). The anticoagulant effect of heparin and synthetic polysaccharide-

Raad, I., et al. (1997). Central Venous Catheters Coated with Minocycline and Rifampin for the Prevention of Catheter-Related Colonization and Bloodstream Infections.Ann.

Reid, G. (2001). Oral fuoroquinolone theraphy results in drug adsorption on ureteral stents and prevention of biofilm formation.Int. J. Antimicr. Ag. Vol. 17, pp. 317-320. Roy, R. K. and K.-R. Lee (2007). Biomedical applications of diamond-like carbon coatings: A review.J. Biomed. Mater. Res. Part B: Appl. Biomater. Vol. 83, No B,pp. 72-84. Ruggieri, M. R., et al. (1987). Reduction of bacterial adherence to catheter surface with

Tenke, P., et al. (2004). Bacterial biofilm formation on urologic devices and heparin coating

Voevodin, A. A. and M. S. Donley (1996). Preparation of amorphous diamond-like carbon by pulsed laser deposition: a critical review.Surface and Coatings Technology Vol. 82,

Warren, J. W., et al. (1994). Long-term urethral catheterization increases risk of chronic pyelonephritis and renal inflammation.J. Am. Geriat. Soc. Vol. 42, No 12,pp. 1286-1290. Zdrahala, R. J. and I. J. Zdrahala (1999). Biomedical application of polyurethanes: A review of past promises, present realities, and a vibrant future.J. Biomater. Appl. Vol. 14, pp.

as preventive strategy Int. J. Antimicr. Ag. Vol. 23, No S1,pp. 67-74.

polysulphuric acid esters.Acta Pharmacol. Vol. 2, pp. 138-148.

Polyurethanes (PU) are an important class of polymers that have found many applications as biomaterials due to their excellent physical properties and relatively good biocompatibility. Basically, PU may be produced by two chemical processes: by polycondensation of a diamine with bischloroformates or by reaction between a diol and a diisocyanate. Many biomedical devices are made from segmented PU such as catheters, blood pumps, prosthetic heart valves and insulation for pacemakers (Lelah & Cooper, 1986, Lamba et al., 1997). A promising approach for the development of new controlled-releasing preparations is use of PU as the carriers in drug delivery systems.

Drug delivery systems have been progressively developed in the field of therapeutic administration owing to their advantages: providing drug concentration over a period of prolonged action, decreasing the total therapeutic dose and reducing the undesirable side effects, and, hence, improving the pharmaceutical efficiencies. These are achieved by the use of the controlled-release drug delivery systems (Hsien, 1988). Controlled release dosage forms are consist of the pharmacological agent and the polymer carrier that regulate its release. In general two types of drug delivery systems have been used: diffusion-controlled systems and dissolution-controlled systems. In the first cause the drug is usually dispersed or dissolved in the solid reservoir or membrane and the kinetics of drug release are generally controlled by diffusion through the polymer. In the second cause the drug are generally incorporated into a water-soluble or water-swellable polymer and the release of drug is controlled by swelling and dissolution of polymer. In both the causes polymer function is a principal component which controls the transport and the release rate of drug molecule. To be a useful drug carrier, a polymer needs to possess certain features. The polymeric carrier has to be non-toxic, non-immunogenic and biocompatible; the carrier must contain an effective dose of active agent; the material of system must be biodegradable and

© 2012 Batyrbekov and Iskakov, licensee InTech. This is an open access chapter distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2012 Batyrbekov and Iskakov, licensee InTech. This is a paper distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

form biologically acceptable degradation products; the rate of drug release from the carrier must occur at an acceptable rate; the carrier must be able to be easily sterilized.

Polyurethane as Carriers of Antituberculosis Drugs 149

foams. The effects of nature and concentration of drugs and diols, molecular weight (Mw), morphology of polyurethanes on release behavior from polymeric systems were studied. The possibility of application of the polymeric drug delivery systems based on polyurethane

Recent trends in polymeric controlled drug delivery have seen microencapsulation of pharmaceutical substances in biodegradable polymers as an emerging technology. Extensive progressive efforts have been made to develop various polymeric drug delivery systems to either target the site of tuberculosis infection or reduce the dosing frequency (Toit et al., 2006). Carriers as microspheres have been developed for the sustained delivery of antituberculosis drugs and have demonstrated better chemotherapeutic efficacy when investigated in animal models. Antituberculosis drugs have been successfully entrapped in microparticles of natural and synthetic polymers such as alginate (ALG), ALG-chitosan, poly-lactide-co-glycolide and poly-butyl cyanoacrylate (Gelperina et al., 2005, Pandey &

ALG, a natural polymer, has attracted researchers owing to its ease of availability, compatibility with hydrophobic as well as hydrophilic molecules, biodegradability under physiological conditions, lack of toxicity and the ability to confer sustained release potential. The ability of ALG to co-encapsulate multiple antitubercular drugs and offer a controlled release profile is likely to have a major impact in enhancing patient compliance for better

Spherical microspheres able to prolong the release of Is were produced by a modified emulsification method, using sodium ALG as the hydrophilic carrier (Rastogi et al., 2007). The particles were heterogeneous with the maximum particles of an average size of 3.719 μm. Results indicated that the mean particle size of the microspheres increased with an increase in the concentration of polymer and the cross-linker as well as the cross-linking time. The entrapment efficiency was found to be in the range of 40-91%. Concentration of the cross-linker up to 7.5% caused increase in the entrapment efficiency and the extent of drug release. Optimized Is-ALG microspheres were found to possess good bioadhesion. The bioadhesive property of the particles resulted in prolonged retention in the small intestine. Microspheres could be observed in the intestinal lumen at 4h and were detectable in the intestine 24h post-oral administration. Increased drug loading (91%) was observed for the optimized formulation suggesting the efficiency of the method. Nearly 26% of Is was released in simulated gastric fluid pH 1.2 in 6h and 71.25% in simulated intestinal fluid pH

ALG microparticles were developed as oral sustained delivery carriers for antituberculosis drugs in order to improve patient compliance (Qurrat-ul-Ain et al., 2003). Pharmacokinetics and therapeutic effects of ALG microparticle encapsulated Is, rifampicin and pyrazinamide were examined in guinea pigs. ALG microparticles containing antituberculosis drugs were evaluated for in vitro and in vivo release profiles. These microparticles exhibited sustained

for tuberculosis treatment was shown by some medical and biological tests.

**2. Polymeric microparticles for tuberculosis treatment** 

management of tuberculosis (Ahmad & Khuller, 2008).

Khuller, 2006).

7.4 in 30h.

The design of the PU controlled-release forms for therapeutic drug administration is the subject of intense interest. Such systems are being used for sustained and controlled delivery of various pharmaceutical agents such as prednisolon (Sharma et al., 1988), morphine, caffeine (Graham et al., 1988), prostaglandin (Embrey et al., 1986) and theophylline (Reddy et al., 2006). The PU carrier is utilized to deliver iodine-containing drugs (Touitou & Friedman, 1984). Urethane-based hydrogels were prepared based on the reaction of diisocyanates with amphilic ethylene oxide and triol crosslinker to deliver propranolol hydrochloride, an antihypertensive drug (Van Bos & Schacht, 1987). Drug delivery systems on a PU base with various antitumorous drugs, such as cyclophosphane, thiophosphamide and vincristine, have been prepared (Iskakov et al., 1998, 2000). An in vitro technique was used to determine the release characteristics of the drugs into model biological media. It was shown the drug release occurs in accordance with first-order kinetics.

PU-based drug delivery systems have considerable potential for treatment of tuberculosis. Tuberculosis is widely spread disease in most developing countries. The main method of tuberculosis treatment is chemotherapy. Although current chemotherapeutic agents for tuberculosis treatment are therapeutically effective and well tolerated, a number of problems remain. The chemotherapy is burden some, extends over long periods and requires continuous and repeated administration of large drug doses. Thus, traditional drug chemotherapy has serious limitations because of increasing microbial drug resistance and toxico-allergic side effects. One of the ultimate problems in effective treatment of tuberculosis is patient compliance. These problems of increasing drug resistance, toxicoallergic side effects, patient compliance can be approached by the use of long-acting polymeric drug delivery systems (Sosnik et al., 2010). The design of implantable systems containing the antituberculosis drugs in combination with biocompatible polymers would make possible to achieve the significant progress in treatment of this global debilitating disease *(*Shegokar et al., 2011).

Biodegradable microsphere drug delivery systems have shown application for oral and parenteral administration. Administration of microparticles to the lungs (alveolar region) may provide the opportunity for the prolonged delivery active agent to tuberculosis infected macrophages. Microspheres can be produced to meet certain morphological requirements such as size, shape and porosity by varying the process parameters. However, the morphology of the lung is such that to achieve effective drug deposition it is necessary to control the particle size of microparticles.

The objective of the chapter is to develop an effective polymeric drug delivery systems based on PU for the treatment of tuberculosis. Polyurethane materials are investigated as carriers for sustained and controlled release of antituberculosis drugs. The synthesis and characterization of PU microcapsules are studied making use various molecular weight polyethylene glycol and tolylene-2,4-diisocyanate. Antituberculosis drug isoniazid (Is), rifampicin, ethionamide and florimicin were incorporated into the PU microcapsules and foams. The effects of nature and concentration of drugs and diols, molecular weight (Mw), morphology of polyurethanes on release behavior from polymeric systems were studied. The possibility of application of the polymeric drug delivery systems based on polyurethane for tuberculosis treatment was shown by some medical and biological tests.
