Patients treated with conventional cancer chemotherapy suffer from side effects of the drugs due to non-selective action of chemotherapeutic drugs to normal cells. Active targeting nanoparticles that are conjugated to targeting ligands on the surface of nanoparticles play an important role in improving drug selectivity to the cancer cell. Several chemotherapeutic drugs and traditional/herbal medicines reported for anticancer activities have been investigated for their selective delivery to cancer cells by active targeting nanoparticles. This systematic review summarizes reports on this application. Literature search was conducted through PubMed database search up to March 2017 using the terms nanoparticle, chemotherapy, traditional medicine, herbal medicine, natural medicine, natural compound, cancer treatment, and active targeting. Out of 695 published articles, 61 articles were included in the analysis based on the predefined inclusion and exclusion criteria. The targeting ligands included proteins/peptides, hyaluronic acid, folic acid, antibodies/antibody fragments, aptamer, and carbohydrates/polysaccharides. In vitro and in vivo studies suggest that active targeting nanoparticles increase selectivity in cellular uptake and/or cytotoxicity over the conventional chemotherapeutic drugs and non-targeted nanoparticle platform, particularly enhancement of drug efficacy and safety. However, clinical studies are required to confirm these findings.

Background: Cholangiocarcinoma is a serious public health in Thailand with increasing incidence and mortality rates. The present study aimed to investigate cytotoxic activities of crude ethanol extracts of a total of 28 plants and 5 recipes used in Thai folklore medicine against human cholangiocarcinoma (CL-6), human laryngeal (Hep-2), and human hepatocarcinoma (HepG2) cell lines in vitro. Methods: Cytotoxic activity of the plant extracts against the cancerous cell lines compared with normal cell line (renal epithelial cell: HRE) were assessed using MTT assay. 5-fluorouracil was used as a positive control. The IC₅₀ (concentration that inhibits cell growth by 50%) and the selectivity index (SI) were calculated. Results: The extracts from seven plant species (Atractylodes lancea, Kaempferia galangal, Zingiber officinal, Piper chaba, Mesua ferrea, Ligusticum sinense, Mimusops elengi) and one folklore recipe (Pra-Sa-Prao-Yhai) exhibited promising activity against the cholangiocarcinoma CL-6 cell line with survival of less than 50% at the concentration of 50 μg/ml. Among these, the extracts from the five plants and one recipe (Atractylodes lancea, Kaempferia galangal, Zingiber officinal, Piper chaba, Mesua ferrea, and Pra-Sa-Prao-Yhai recipe) showed potent cytotoxic activity with mean IC₅₀ values of 24.09, 37.36, 34.26, 40.74, 48.23 and 44.12 μg/ml, respectively. All possessed high activity against Hep-2 cell with mean IC₅₀ ranging from 18.93 to 32.40 μg/ml. In contrast, activity against the hepatoma cell HepG2 varied markedly; mean IC₅₀ ranged from 9.67 to 115.47 μg/ml. The only promising extract was from Zingiber officinal (IC₅₀ = 9.67 μg/ml). The sensitivity of all the four cells to 5-FU also varied according to cell types, particularly with CL-6 cell (IC₅₀ = 757 micromolar). The extract from Atractylodes lancea appears to be both the most potent and most selective against cholangiocarcinoma (IC₅₀ = 24.09 μg/ml, SI = 8.6). Conclusions: The ethanolic extracts from five plants and one folklore recipe showed potent cytotoxic activity against CL-6 cell. Sensitivity to other cancerous cell lines varied according to cell types and the hepatocarcinoma cell line. HepG2 appears to be the most resistant to the tested extracts.

The poor pharmacokinetic characteristics of most anticancer drugs have limited their clinical effectiveness. The application of nanoparticles as a novel drug delivery system has provided opportunities to tackle the current challenges facing conventional drug delivery systems such as poor pharmacokinetics, lack of specificity to tumor cells, multidrug resistance, and toxicity. This systematic review aims to examine the application of pharmacokinetic studies of nanoparticles loaded in conventional drugs and herb-derived compounds for cancer therapy. The pharmacokinetic parameters of several herbal medicines and chemotherapeutic drugs loaded into nanoparticles were reported. This included area under the curve (AUC) of plasma concentration-time profile, maximum plasma concentration (Cmax), time to maximum plasma concentration (Tmax), volume of distribution (Vd or Vss), elimination half-life (t½), and clearance (CL). The systematic review was conducted using information available in the PubMed and Science Direct databases up to February 2019. The search terms employed were: pharmacokinetics, pharmacokinetic study, nanoparticles, anticancer, traditional medicine, herbal medicine, herb-derived compounds, natural products, and chemotherapy. Overall, nanoparticle carriers not only significantly improved pharmacokinetics but also further enhanced permeability, solubility, stability, specificity, and selectivity of the carried anticancer drugs/herb-derived compounds to target tumor cells. Additionally, they also limited hepatic first-pass metabolism and P-glycoprotein (P-gp) efflux of the carried anticancer drugs/herb-derived compounds. Based on this systematic review, polymeric nanoparticles were the most commonly used nanocarrier to improve the pharmacokinetic parameters. The use of nanoparticles as a novel drug delivery system has the potential to improve both pharmacokinetics and cytotoxicity activity of the loaded drugs/herb-derived compounds for cancer therapy.

What is known and objective Genetic polymorphism is one of the most important factors responsible for interindividual and interethnic variability in drug response. Studies in major populations, ie, Caucasians, Asians, and Africans, have provided evidence of differences in the genotype frequencies of major drug‐metabolizing enzyme cytochrome P450 (CYP). This study aimed to review systematically, all relevant articles related to the genetic polymorphisms in CYP2C9, CYP2C19, CYP2D6 and CYP3A5 in South‐East and East Asian (SEEA) populations. Methods Articles that report genetic polymorphisms, genotype frequencies and allele frequencies in CYP2C9, CYP2C19, CYP2D6 and CYP3A5 were retrieved from the PubMed database. Results and discussions A total of 86 studies that fulfilled the eligibility criteria representing different ethnic populations of SEEA, ie, Burmese, Chinese, Japanese, Karen ethnic minority, Korean, Malaysian, Philippino, Singaporean, Taiwanese, Thai, Indonesian, and Vietnamese, were included in the analysis. In general, the genotype frequencies across SEEA populations are comparable. The CYP2C9*1/*1 (69.3%‐99.1%), *1/*3 (2.3%‐20.1%) and *3/*3 (0%‐2.2%) genotypes are reported in most SEEA populations. Six major CYP2C19 genotypes, ie, *1/*1 (6.25%‐88.07%), *1/*2 (21.5%‐86.46%), *1/*3 (0.8%‐15.8%), *2/*2 (3.4%‐14.5%), *2/*3 (0%‐7.3%) and *3/*3 (0%‐10.2%), are reported in most SEEA populations. Major CYP2D6 genotypes include *10/*10 (0%‐69.6%), *1/*1 (0%‐61.21%) and *1/*10 (0%‐62.0%). Major CYP3A5 genotypes are *3/*3 (2.0%‐71.4%), *1/*3 (16.0%‐57.1%) and *1/*1 (0%‐82.0%). Genotyping of abnormal genotypes of CYP2C9 (*1/*3), CYP2C19 (*1/*2, *1/*3), CYP3A5 (*1/*3) and CYP2D6 (*5/*10) associated with IM (Intermediate metabolizer) status, may be clinically beneficial in SEEA populations. Similarly, with CYP2C19 (*2/*2, *2/*3), CYP2D6 (*5/*5 ) linked to PM (Poor metabolizer), CYP2D6 (*10/*10, *1/*5 and to lesser extent *1/*4, *2/*5, *10/*41, *10/*49, *10/*14) and CYP3A5 (*1/*1) associated with EM (extensive metabolizer). What is new and conclusion Sufficient number of studies has provided comparable results in general. This review suggests that comparable genotype frequencies of CYP2C9, CYP2C19, CYP2D6 and CYP3A5 exist among the SEEA populations. It is noted that more research data are reported from East Asians compared with South‐East Asians. Concerned efforts are required to establish partnerships among SEEA countries that will ensure sufficient data from South‐East Asian countries which will assist in establishing the databases for SEEA populations.