AIMTo investigate the mechanisms of action of transportation of liposomes and chitosan-coated liposomes containing leuprolide across rat intestine and Caco-2 cell.

METHODSEverted-gut technique and Caco-2 cell were used to study the transport properties of free leuprolide, liposomes and chitosan-coated liposomes containing leuprolide. Caco-2 cell was used to study the effect of chitosan concentration and the order of addition on the permeation of liposomes.

RESULTSThe transport of leuprolide was passive diffusion. Probably because the entrapment by liposomes prevents the transport of leuprolide across the rat intestine and Caco-2 cell, the permeation amount of leuprolide from liposomes was lower than that of the free drug. However, liposomes protected the leuprolide from degradation. Chitosan promoted the transport of leuprolide from liposomes and there was no obvious difference in enhancement effect from the concentration of 0.1% to 0.5%. On the other hand, the incubation of chitosan with liposomes may weak the enhancement effect of chitosan.

CONCLUSIONChitosan-coated liposomes showed both protection and enhancement effect, therefore, they may promote the oral absorption of leuprolide.

Animals ; Antineoplastic Agents, Hormonal ; administration & dosage ; pharmacokinetics ; Biological Transport ; drug effects ; Caco-2 Cells ; Chitosan ; chemistry ; pharmacology ; Drug Carriers ; Drug Delivery Systems ; Humans ; Jejunum ; metabolism ; Leuprolide ; administration & dosage ; pharmacokinetics ; Liposomes ; Particle Size ; Permeability ; Rats ; Rats, Sprague-Dawley

PURPOSE: We investigated the protective effects of the herbal formulation KH-204 in the bladder of androgen-deprived rats. MATERIALS AND METHODS: Male rats aged eight weeks were randomly divided into four groups, containing eight rats each: sham operation only (normal control group), androgen-deprived only (androgen-deprived control group), and androgen-deprived followed by treatment with 200 mg/kg or 400 mg/kg of KH-204. After 0.5 mg/kg of leuprorelin was subcutaneously injected in the androgen-deprived groups, the oral administration of either distilled water in the two control groups or KH-204 in the treatment group was continued for four weeks. Serum testosterone levels, RhoGEF levels, nitric oxide (NO)-cyclic guanosine monophosphate (cGMP)-related parameters, oxidative stress, and histologic changes were evaluated after treatment. RESULTS: Treatment with the herbal formulation KH-204 (1) increased serum testosterone levels; (2) restored the expression of RhoGEFs, endothelial NO synthase, and neuronal NO synthase; (3) increased the expression of superoxide dismutase; and (4) decreased bladder fibrosis. CONCLUSIONS: Our results suggest that the positive effects of KH-204 on the urinary bladder may be attributed to its antioxidant effects or to an elevation in NO-cGMP activity.
Administration, Oral ; Animals ; Antioxidants ; Fibrosis ; Guanosine Monophosphate ; Humans ; Hypogonadism ; Leuprolide ; Male ; Neurons ; Nitric Oxide ; Nitric Oxide Synthase ; Oxidative Stress ; Phytotherapy ; Rats* ; Rho Guanine Nucleotide Exchange Factors ; Superoxide Dismutase ; Testosterone ; Urinary Bladder* ; Water

PURPOSE: Granulomas resulting from the administration of luteinizing hormone-releasing hormone analogues (LH-RH analogues) are thought to be very rare. We report on our clinical experience with injection-site granulomas that result from the administration of LH-RH analogues, and we evaluate the incidence rate of these granulomas. MATERIALS AND METHODS: We used the clinical records of 118 patients who were administered LH-RH analogues in 2005. We describe the clinical data of patients who experienced injection-site granulomas and evaluated the incidence rate. RESULTS: Five patients demonstrated injection-site granulomas due to LH-RH analogue administration. The incidence rate was 4.2% (5 of 118 patients). Most of the granulomas occurred after the first or second administration of 11.25mg of leuprorelin acetate. CONCLUSION: The occurrence of granulomas resulting from the administration of LH-RH analogues was thought to be very rare. Our study, however, revealed a higher incidence rate than expected, especially for leuprorelin acetate.
Aged ; Aged, 80 and over ; Antigens, CD/analysis ; Antigens, CD3/analysis ; Antigens, Differentiation, Myelomonocytic/analysis ; Antineoplastic Agents, Hormonal/administration & dosage/adverse effects ; Gonadotropin-Releasing Hormone/administration & dosage/*adverse effects/analogs & derivatives ; Goserelin/administration & dosage/adverse effects ; Granuloma/*etiology/metabolism/pathology ; Humans ; Injections, Subcutaneous/adverse effects ; Leuprolide/administration & dosage/adverse effects ; Male ; Prostatic Neoplasms/*drug therapy

The increased survival of patients with breast cancer has given rise to other problems associated with the complications of chemotherapy. One major complication is premature ovarian failure, an especially harmful outcome for women of reproductive age. This study was performed to evaluate the efficacy of GnRH agonist (GnRHa) treatment on protecting ovarian function in young breast cancer patients (30.59+/-5.1 yr) receiving chemotherapy after surgery. Twenty-two women were enrolled and given subcutaneous injections of leuprolide acetate (3.75 mg) every 4 weeks during chemotherapy. Follow-up laboratory tests (luteinizing hormone [LH], follicle stimulating hormone [FSH], and estradiol) were performed 1, 3, and 6 months after chemotherapy. Menstruation patterns and clinical symptoms were followed up for a mean duration of 35.6+/-1.7 months. FSH and LH levels were normal in all patients 6 months after completing chemotherapy (8.0+/-5.3, 4.4+/-2.7 mIU/mL, respectively). During follow-up, none of the patients complained of menopausal symptoms and 81.8% experienced recovery of menstruation. This report is the first trial of GnRHa as a treatment modality to protect ovarian function during adjuvant chemotherapy in young Korean breast cancer patients.
Adult ; Antineoplastic Agents/adverse effects/therapeutic use ; Antineoplastic Agents, Hormonal/therapeutic use ; Breast Neoplasms/diagnosis/*drug therapy/surgery ; Combined Modality Therapy ; Cyclophosphamide/adverse effects/therapeutic use ; Doxorubicin/adverse effects/therapeutic use ; Female ; Follicle Stimulating Hormone/analysis ; Gonadotropin-Releasing Hormone/*agonists ; Humans ; Leuprolide/administration & dosage ; Luteinizing Hormone/analysis ; Menstruation ; Ovarian Function Tests ; Primary Ovarian Insufficiency/etiology/*prevention & control ; Republic of Korea ; Tamoxifen/therapeutic use ; Time Factors