Scleral plug of biodegradable polymers for controlled drug release in the vitreous.

We designed a new device, a scleral plug, that releases drugs into the vitreous after being implanted and fixed at the pars plana. Use of the plug for provision of doxorubicin hydrochloride was evaluated in rabbits. The scleral plug (8.5 mg) was made of poly(lactic-glycolic acid) (molecular weight, 40,000 daltons) containing 1% doxorubicin. Vitreous concentrations of doxorubicin were measured after the implantation. In vitro studies showed that the plug released 26% of the drug during 4 weeks. In vivo studies demonstrated that the concentration in the vitreous humor was maintained at a therapeutic range for longer than 4 weeks. No substantial toxic reactions were observed by electroretinographic and histopathologic evaluations. Our findings suggested that a scleral plug made of biodegradable polymers is a promising device for a controlled drug-release system in the vitreous.

The side-effects of ciclosporine-A and tacrolimus.

Ciclosporine-A (CSA) has been in clinical use as an immunosuppressive drug in transplant recipients for over a decade. Unfortunately, CSA also has major side-effects (including nephrotoxic ones). In an attempt to find safer agents, tacrolimus (TAC) has been introduced recently. Despite major differences in the chemical structure, TAC and CSA seem to have many effects in common. This phenomenon can be explained by the inhibition of the calcineurin pathway characteristic for both drugs. The aim of our brief review was to compare personal observations regarding side-effects encountered under CSA or TAC therapy with data reported previously. We found that the profile of side-effects both under CSA and TAC was nearly identical. In particular, morphologic changes associated with toxic drug effects in the kidney were indistinguishable from one another, i.e. tubular lesions, arteriolopathy, HUS-like changes in glomeruli and vessels. The prevalence of defined nephrotoxic lesions was very similar. Some differences were found regarding the prevalence of clinical side effects. Hypertension, hypertrichosis and gingival hyperplasia were less pronounced in the TAC group and an elevated blood glucose level in the CSA group. We conclude that TAC and CSA are closely related immunosuppressive drugs with regard to adverse effects.

[Clinical effect on tumor regression and tissue concentration of peplomycin treated with peplomycin emulsion in hydroxypropylcellulosum].

Peplomycin emulsified in hydroxypropyl cellulosum (HPC-PEP) was prepared for intravesical chemotherapy. Clinical efficacy of HPC-PEP and tissue concentration of peplomycin (PEP) were studied in 12 patients with bladder tumor. Histopathology showed transitional cell carcinoma; 2 in grade 1,8 in grade 2, and 2 in grade 3. The total volume of 30 ml HPC-PEP was prepared from a mixture of 2% HPC and 90 mg PEP in 15 ml saline, and was intravesically administered through a urethral catheter and retained for two hours. Clinical evaluation 7 days after the initial instillation demonstrated good tumor regression in 2, good response in 5, and no change in 5. The mean PEP level in tumor tissue was 0.36 microgram/gr after 7 days and 0.19 microgram/gr even after 14 days. These clinical observations and tissue levels of PEP suggest that HPC-PEP might be useful as an intravesical instillation agent for bladder tumor.