Cisplatin suppository: preparation, release characteristics and clinical evaluation.

Area of Science:

• Oncology
• Pharmacology
• Drug Delivery Systems

Background:

• Cisplatin (CDDP) is a key chemotherapy for uterine endometrial carcinoma.
• CDDP treatment is limited by severe side effects, notably renal toxicity.
• Novel drug delivery systems are needed to enhance CDDP efficacy and reduce toxicity.

Purpose of the Study:

• To develop and evaluate cisplatin suppositories containing sodium chloride (NaCl) for uterine endometrial carcinoma.
• To investigate the effect of NaCl concentration on CDDP release, suppository properties, and clinical efficacy.
• To assess CDDP absorption and safety profile in patients with endometrial carcinoma.

Main Methods:

• Formulation of CDDP suppositories with varying NaCl concentrations.
• In vitro characterization of release rate, melting point, and viscosity.
• Clinical administration of a 0.06% NaCl CDDP suppository to three patients.
• Monitoring of serum platinum (Pt) levels and endometrial absorption via radiographic analysis.

Main Results:

• Increased NaCl concentration enhanced CDDP release rates.
• NaCl addition raised suppository melting point and significantly increased viscosity.
• Clinical trials showed Pt particles in necrosed endometrial tissue.
• Patients exhibited variable peak plasma Pt levels but no reported CDDP side effects.

Conclusions:

• CDDP suppositories with NaCl offer a promising approach for endometrial carcinoma treatment.
• The formulation potentially enhances localized drug delivery and reduces systemic toxicity.
• Further research is warranted to optimize dosage and confirm therapeutic benefits.