Celia M. Bell

Recent advances in arsenic trioxide encapsulated nanoparticles as drug delivery agents to solid cancers

Since arsenic trioxide was first approved as the front line therapy for acute promyelocytic leukemia 25 years ago, its anti-cancer properties for various malignancies have been under intense investigation. However, the clinical successes of arsenic trioxide in treating hematological cancers have not been translated to solid cancers. This is due to arsenics rapid clearance by the bodys immune system before reaching the tumor site. Several attempts have henceforth been made to increase its bioavailability toward solid cancers without increasing its dosage albeit without much success. This review summarizes the past and current utilization of arsenic trioxide in the medical field with primary focus on the implementation of nanotechnology for arsenic trioxide delivery to solid cancer cells. Different approaches that have been employed to increase arsenics efficacy, specificity and bioavailability to solid cancer cells were evaluated and compared. The potential of combining different approaches or tailoring delivery vehicles to target specific types of solid cancers according to individual cancer characteristics and arsenic chemistry is proposed and discussed.Since arsenic trioxide was first approved as the front line therapy for acute promyelocytic leukemia 25 years ago, its anti-cancer properties for various malignancies have been under intense investigation. However, the clinical successes of arsenic trioxide in treating hematological cancers have not been translated to solid cancers. This is due to arsenics rapid clearance by the bodys immune system before reaching the tumor site. Several attempts have henceforth been made to increase its bioavailability toward solid cancers without increasing its dosage albeit without much success. This review summarizes the past and current utilization of arsenic trioxide in the medical field with primary focus on the implementation of nanotechnology for arsenic trioxide delivery to solid cancer cells. Different approaches that have been employed to increase arsenics efficacy, specificity and bioavailability to solid cancer cells were evaluated and compared. The potential of combining different approaches or tailoring delivery vehicles to target specific types of solid cancers according to individual cancer characteristics and arsenic chemistry is proposed and discussed.

Effective Delivery of Arsenic Trioxide to HPV-Positive Cervical Cancer Cells Using Optimised Liposomes: A Size and Charge Study

Despite the success of arsenic trioxide (ATO) in treating haematological malignancies, its potential to treat solid tumours has not been fully exploited, owing to its dose-limiting toxicity and poor pharmacokinetics. In order to overcome this hurdle, liposomal encapsulation of the drug with different surface charges (neutral, negative, and positive) and sizes (100, 200 and 400 nm) were synthesised and tested on human papilloma virus (HPV)-positive HeLa and HPV-negative HT-3 cervical cancer cell lines. Two epithelial cell lines—human keratinocytes (HK) and human colon cells (CRL-1790)—were used as controls. The synthesised liposomes were tested for their physico-chemical characteristics, drug loading efficiency, and toxicity on the studied cell lines. Neutral liposomes of 100 nm in size were the chosen formulation for delivering ATO into the studied cells, as they showed the least intrinsic cytotoxicity and the highest loading efficiency. The findings demonstrated that the optimised formulation of liposomes was an effective drug delivery method for HPV-infected cervical cancer cells. Furthermore, the toxicity vs. uptake ratio was highest for HeLa cells, while a reduced or minimal toxic effect was observed for non-HPV-infected cervical cancer cells and control cells. These findings may provide a promising therapeutic strategy for effectively managing cervical cancers.

Antiinflammatory and hepatoprotective medicinal herbs as potential substitutes for bear bile

Practitioners of traditional Chinese medicine (TCM) commonly prescribe medicinal formulations relying on the purported synergism of a combination of plant species, sometimes incorporating animal parts and minerals. Bear bile, obtained from either wild or farmed bears, is a commonly used constituent of traditional medicine formulations. With several bear species now listed under Convention on International Trade in Endangered Species of Wild Fauna and Flora as threatened with extinction and with bear farming being actively campaigned against on ethical grounds, it is important to seek and promote alternatives to the use of bear bile as medicine. This chapter describes and evaluates the scientific data relating to the efficacy of bear bile and potential alternatives to its use, including the use of bile from other animal species, the use of synthetic chemical alternatives, and the use of herbal substitutes. Scientific studies have confirmed the efficacy of bear bile as an antiinflammatory and a hepatoprotective agent. Ursodeoxycholic acid (UDCA), the active component of bear bile is used in a synthetic form in Western medicine and can serve as an alternative to bear bile in the treatment and management of certain cholestatic liver conditions. In TCM practice, bile from domesticated animal species (such as cattle, chicken, and pig) has been used as a substitute for bear bile. Following evaluation of TCM literature and pharmacological/clinical data, the authors propose six plant species, either as single herbs or in combination, Gardenia jasminoides (zhī zi; ), Scutellaria baicalensis (huáng qín; ), Coptis chinensis (huáng lián, ), Phellodendron amurense (huáng băi; ), Andrographis paniculata (chuan xin lian; ), and Rheum palmatum (dà huang; ), two medicinal Kampo formulations, Orengedokuto, Dia-Orengedokuto (which originated from traditional Chinese herbal formula Huanglian Jiedu Tang, ), and two individual phytochemicals (berberine and andrographolide) as alternatives to bear bile. The proposed herbal alternatives are frequently found listed in traditional formulations also containing bear bile, usually with different therapeutic roles ascribed to them. The existing evidence base for the effectiveness of herbal alternatives is sufficiently strong for TCM practitioners and consumers to consider using these without the addition of bear bile. This consideration is driven by the imperative to protect populations of bears from overexploitation in the wild and when farmed. However, for the identified alternatives to be accepted by users, it is essential that researchers and TCM practitioners collaborate effectively to initiate consumer behavior change.

Liposome‑delivered baicalein induction of myeloid leukemia K562 cell death via reactive oxygen species generation

Baicalein (BL), a potential cancer chemopreventative flavone, has been reported to inhibit cancer cell growth by inducing apoptosis and causing cell cycle arrest in various human cancer cell models. Delivery of BL via nanoliposomes has been shown to improve its oral bioavailability and long-circulating property in vivo. However, the role of BL in the inhibition of human chronic myeloid leukemia (CML) K562 cell growth and its underlying mechanisms has yet to be elucidated. In the present study, BL was formulated into liposomes with different sizes to improve its solubility and stability. The cytotoxic and pro-apoptotic effects of free BL and liposomal BL were also evaluated. The results demonstrated that 100 nm liposomes were the most stable formulation when compared with 200 and 400 nm liposomes. Liposomal BL inhibited K562 cell growth as efficiently as free BL (prepared in DMSO), indicating that the liposome may be a potential vehicle to deliver BL for the treatment of CML. Flow cytometry analysis showed that there was significant (P<0.005) cell cycle arrest in the sub-G1 phase (compared with vehicle control), indicating cell apoptosis following 20 µM liposomal BL or free BL treatment of K562 cells for 48 h. The induction of cell apoptosis by all BL preparations was further confirmed through the staining of treated cells with Annexin V-fluorescein isothiocyanate/propidium iodide. A significant increase in reactive oxygen species (ROS) generation was observed in free BL and liposomal BL treated cells, with a higher level of ROS produced from those treated with free BL. This indicated that cell apoptosis induced by BL may be via ROS generation and liposome delivery may further extend the effect through its long-circulating property.