G. Giammona et al., A NEW WATER-SOLUBLE SYNTHETIC-POLYMER, ALPHA,BETA-POLYASPARTHYDRAZIDE, AS POTENTIAL PLASMA EXPANDER AND DRUG CARRIER, Journal of controlled release, 29(1-2), 1994, pp. 63-72
The reaction between a polysuccinimide (PSI) and hydrazine produces a
water-soluble polymer alpha,beta-polyasparthydrazide (PAHy). Tests of
the polymer on laboratory animals established its potential use as a p
lasma substitute. Acute toxicity studies revealed no death in the anim
als treated, and subacute toxicity studies recorded no notable differe
nce between treated and control animals either in terms of body-weight
or the principle haematological parameters. Haemodynamic studies like
wise established no significant variation in systolic and diastolic pr
essure or in heart beat between the two groups. Solutions of PAHy admi
nistered to bled animals improved the lowering of blood values caused
by the bleeding. Moreover, PAHy was not capable of inducing any immune
response when administered intradermally to laboratory animals. The p
otential use of PAHy as a drug carrier was also investigated. PAHy was
bonded with a model drug, the antibacterial Ofloxacin, by means of a
water-soluble carbodiimide, N-ethyl-N'-(3-dimethylaminopropyl) carbodi
imide hydrochloride (EDC). The resulting conjugate, PAHy-Ofloxacin is,
like the polymeric carrier, water-soluble and contains a quantity of
linked drug equivalent to 9% (w/w).