**6. Conclusion**

164 Polyurethane

Is

Eth

Fl

Rfp

at 37oC for initial stage of release.

therapy is presented in Table 2.

Group

Drug Loading

(mg/g PU)

Physiological solution

**Table 1.** Diffusion coefficient (D) values for drug release from polyurethane foams into different media

The efficiency of tuberculosis treatment by PU containing drugs was studied in experiments on guinea pigs (Batyrbekov et al., 1998). Several groups of animals, consisting of 20-25 guinea pigs, were infected with a 6-week culture of a laboratory strain of *M. tuberculosis.*  Treatment was started 2 weeks after infection. Animals were treated by weekly administration of PU containing 5-day doses of the drugs (PU-Is, PU-Eth or PU-Fl), or by daily administration of a day's dose of Is, Eth or Fl. Animals of the control group were not treated (C). The weights of the guinea pigs and the dimensions of ulcers at the site of infection were periodically determined during the experiment. All untreated animals died 1.5-2 months after infection. The animals of the other groups were killed with 2.5 months after the beginning of the treatment. Guinea pigs were dissected and damage to lungs, livers, spleens and lymphatic ganglions was determined. The efficiency of the applied

107 x D (cm2 s-1 )

Phosphate Buffer

Ringer-Locke solution

100 7,482 7,926 7,346 200 7,026 7,150 7,158 300 6,845 6,890 6,804

100 6,433 6,228 6,248 200 6,237 5,928 6,142 300 5,972 5,768 5,636

100 2,124 2,430 2,315 200 1,980 2,068 2,112 300 1,642 1,786 1,720

100 1,116 1,224 1,226 200 0,984 1,082 1,068 300 0,922 0,944 0,896

Index of damage, %

ganglion Summary

Lung Liver Spleen Lymphatic

С 36.6 25,8 22,0 6,0 90,4 Is 5,0 12,2 12,2 2,5 31,9 PU-Is 4,0 11,4 12,0 2,5 29,9 Eth 8,0 13,6 14,6 3,5 39,7 PU-Eth 7,2 13,0 14,2 3,5 37,9 Fl 20,2 14,4 16,8 4,8 56,2 PU-Fl 18,8 13,0 16,6 4,4 52,0

**Table 2.** Macroscopic evaluation of damage to inner organs of guinea pigs.

PU microparticles containing antituberculosis drugs were prepared by interfacial reaction between PEG and TDI in water in toluene emulsion. Two products of polycondensation were detected: the main product is spherical microparticles with size about 5-10 μm and the second product is fibrils of linear PU, which precipitate in toluene. The increase of PEG content in water phase results in increased amount of the secondary product, and as the PEG content in water phase reaches 60 vol.%, maximum of the secondary product was observed (about 40%). Decreasing PEG concentration in water phase leads to increased yield of PU microparticles. Maximum of yield was reached at PEG concentration 22 - 27 vol.% and in that conditions whole oligomer reacted at surface of emulsion drops with microparticles formation.

The release behavior of drugs from microparticles was carried out and different conditions of synthesis such as water/PEG ratio, molecular weight of PEG and drug concentration was investigated. The increase PEG content in water phase of reaction, results in decreasing drug diffusion, due to formation of PU microparticles with densere polymer wall. Increasing molecular weight of soft segments (PEG) results in the increase of diffusion rate of drug into solution. This phenomenon can be attributed to increasing molecular weight of PEG which leads to accelerating diffusion of water-soluble drug through hydrophilic PEG chains. It was shown that microparticles with higher drug loading demonstrate faster release rate of the drug due to increased gradient of concentrations between the external solution and core of microparticles.

The tuberculostatic activity of drugs released from the PU show that drugs introduced into PU have antimicrobial activity identical of low molecular drugs. The efficiency of the tuberculosis treatment by polyurethane drug delivery systems was shown in experiments on animals. The use of PU carrier provides a stable bacteriostatic concentration of the chemotherapeutical agents for 5-7 days. The treatment of animals infected with tuberculosis by PU systems was more effective than the treatment by free drugs. It was shown that is released from PU systems was 1.5-2 times less toxic in comparison with the low molecular drug. Minimal toxic action of PU on the native organism tissue was established hystologically. Medical-biological tests show that PU ensures sustained release of antituberculosis drugs and maintains effective drug concentration for long time.

Polyurethane as Carriers of Antituberculosis Drugs 167

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The results obtained in the present chapter have shown the possibility and outlook of PU as carriers of antituberculosis drugs for the delivery systems for prolonging the action of chemotherapeutical agents in tuberculosis treatment.
