ABSTRACT
Photodynamic therapy (PDT) is a new modality for cancer therapy, which has been used in the clinical treatment for various tumors, such as skin cancer, bladder cancer and prostate cancer. Most photosensitizers have the disadvantages of hydrophobic, low bioavailability and the limited tumor targeting ability. The nanoscale delivery systems can improve the solubility of photosensitizers and enhance their accumulation at the tumor sites. The multifunctional nano-delivery systems are prepared in combination with other anti-tumor drugs to enhance the anti-tumor effect. In addition to addressing the issues of poor solubility and the insufficient tumor targeting ability, the nanoscale delivery systems need to improve the pharmacokinetic properties of photosensitizers, facilitating their rapid accumulation at the tumor sites and quick elimination in vivo, and reducing the skin phototoxicity. This review summarizes the recent clinical application of PDT of cancer, the development of photosensitizers, the delivery systems for photosensitizers and the combinatorial application with other therapeutic methods. The goal is to present an understanding of knowledge on the design of new types of photosensitizers and its clinical application in PDT of cancer.
ABSTRACT
Xenograft mice are preclinical animal models of tumors and are widely utilized in anti-tumor research. PK/PD modeling of anti-tumor agents is an approach that can capture the time profile of the "dose-plasma concentration-biomarker level-tumor volume" process based on experimental data from xenograft mice using a non-linear mixed-effect model. PK/PD modeling can help optimize the dosing regimen for anti-tumor therapy, evaluate any synergistic effect and help identify an optimal schedule for combination therapy, as well as providing a preliminary estimate of a drug's efficacy and anti-tumor potency in the human body. PK/PD modeling can also help by quantitatively explaining the mechanism of the tumor-inhibitory effect as indicated by changes in biomarker levels after a drug acts on its target. This article provides a systematic summary of the background, application range, and limitations of the mainstream anti-tumor agent PK/PD models. Recent advances in model structure development are reviewed in detail. Finally, we discuss promising applications of PK/PD models in anti-tumor medicine development from the perspective of a drug's mechanism of action, optimization of combination therapy schedules, and their clinical translation.
ABSTRACT
The study was conducted to investigate the safety of combined extracts of Bryophyllum pinnatum (family: Crassulaceae) and Aloe barbadensis (family: Xanthorrhoeaceae) in rats. Forty rats were randomly selected and divided into four groups. Rats in groups I were administered with placebo as the control animals, while rats in groups II, III and IV were administered with aqueous extracts at 25mg/ml, 50mg/ml and 100mg/ml respectively for 28 days. Five milliliter (5ml) of blood was collected from either the ocular vein or aorta of each animal for evaluation of baseline and post – treatment values of AST, ALP, ALT, BUN, Total protein, and Creatinine, WBC, RBC, Platelet, MCV, MCH and MCHC. Data were expressed as Mean±Standard Error of Mean and analyzed using oneway ANOVA. Difference of means was considered statistically significant at P<0.05. Quantitative phytochemical assay revealed mainly alkaloids, with one gram each of B. pinnatum and A. barbadensis extracts containing 5.3mg and 9.1mg of alkaloids respectively. Administration of the combined extracts elevated the serum levels of Alkaline phosphatase, Aspartate amino transaminase, Total protein, Creatinine and BUN in the entire rats in test groups especially those in group IV (P<0.05). In ALT, there was no significant variation between the baseline and the post-treatment values especially in animals in groups III and IV (P>0.05). Rats in groups II, III and IV exhibited significant increase in values of WBC, RBC, Platelet, MCV and MCH (P<0.05) while MCHC value for rats in group IV showed insignificant differences when compared to the control rats (P>0.05). Administration of the combined extracts may be tolerated at ≤25mg/kg bodyweight, if prolonged administration is avoided.