In cancer therapy, it is essential to selectively release cytotoxic agents into the tumor to prevent the adverse effects associated with anticancer drugs. Thus, in this study, a stimuli-sensitive polymer–drug conjugate was synthesized for selective drug release. Doxorubicin (DOX) and docetaxel (DTX) were conjugated onto novel poly(jasmine lactone) based copolymer via a thioketal (TK) linker. In addition, a photosensitizer (chlorin e6) was attached to the polymer, which served as a reactive oxygen species generator to cleave the TK linker. The conjugate is readily self-assembled into micelles less than 100 nm in size. Micelles demonstrate a notable increase in their ability to cause cell death when exposed to near-infrared (NIR) light on MDA-MB-231 breast cancer cells. The increase in cytotoxicity is higher than that observed with the combination of free DOX and DTX. The accumulation of DOX in the nucleus after release from the micelles (laser irradiation) was also confirmed by confocal microscopy. In the absence of light, micelles did not show any toxicity while the free drugs were found toxic irrespective of the light exposure. The obtained results suggest the targeted drug delivery potential of micelles regulated by the external stimuli, i.e., NIR light.

Poor aqueous solubility remains a major challenge in drug development, limiting oral bioavailability and therapeutic efficacy. To address this issue, various enabling formulation approaches have been investigated, among which amorphous solid dispersions (ASDs) are considered one of the most effective technologies. However, ASDs performance is largely depending on the physiochemical properties of the carrier polymer, highlighting the need for the development of novel polymers. In this study, a carboxylic acid functionalized poly(jasmine lactone)-based amphiphilic block copolymer (mPEG-b-PJL-COOH) was evaluated as the polymeric carrier for the delivery of posaconazole (PSZ) in form of an ASD. The performance of the mPEG-b-PJL-COOH based ASD was compared with an ASD using poly(vinylpyrrolidone-co-vinyl acetate) (PVPVA64), while Posoxil® (a suspension) and a solubilized form of PSZ (PSZ-loaded polymeric micelles, PM) served as comparator formulations. The formulations were evaluated for their amorphousness (ASDs), drug loading, in vitro drug release (dissolution), and in vivo pharmacokinetic performance. The mPEG-b-PJL-COOH-based ASD showed a significantly improved dissolution profile of PSZ in fasted-state simulated intestinal fluid (FaSSIF), achieving a 5.2-fold and 10.3-fold higher area under the dissolution curve than ASD-PVPVA64 and Posoxil®, respectively. In vivo pharmacokinetic studies revealed that mPEG-b-PJL-COOH ASD and PM formulations increased PSZ exposure by approximately 1.5- and 4.6-times compared with ASD-PVPVA64 and Posoxil®, respectively. Furthermore, mPEG-b-PJL-COOH was well tolerated following acute oral administration in rats at a dose of up to 2 g/kg. Overall, this study demonstrates that mPEG-b-PJL-COOH could serve as a promising alternative to commercially available polymers for enhancing the oral bioavailability of poorly water-soluble drugs.

Lumiracoxib (LXB) was in use for the treatment of rheumatoid arthritis and osteoarthritis but was withdrawn from the market due to severe hepatotoxicity. Nevertheless, nanotechnology-based reformulation of such drug can tailor pharmacokinetics through controlled release and reduced off-target liver accumulation, improving efficacy and safety. Thus, the present study explored the potential of poly(δ-decalactone) (PDL)-based nanoemulsion (NE) to reduce the hepatic toxicity of LXB. Tailor-made diblock (mPEG-b-PDL) and triblock (PDL-b-PEG-b-PDL) co-polymers were used as surfactants, while homopolymers (B-PDL, B-PJL-COOH and B-PJL-OH) were used as polymeric oil to fabricate NEs. NEs prepared using B-PDL (F3 and F4) enhanced the aqueous solubility of LXB by 30.4 ± 5.4 and 37.3 ± 4.8-fold, respectively. In vitro cytotoxicity results revealed that prepared NEs reduced the cytotoxicity of LXB in liver cancer (HepG2) cells by approx. 2-fold. Furthermore, liver toxicity and inflammatory markers were evaluated using Multiplex® after LXB NE treatment and results showed that NEs performed better compared to free LXB. Evaluation in an in vivo arthritic model further demonstrated NEs capability in reducing LXB-induced hepatic toxicity with improved anti-inflammatory activity. These findings suggest that PDL NEs may offer a promising strategy for improving the biopharmaceutical performance and safety profile of LXB.

Clinical trials are an essential testing ground for studying anticancer drugs and other treatments before they can be granted government approval. Over the last decade, numerous anticancer drugs have been evaluated in clinical trials, and many of them have been approved for cancer treatment. Fourteen new cancer therapeutics with different mechanisms were launched in 2017 alone, and 11 of them received breakthrough therapy designations from the FDA. In the present article, we review the numerous anticancer drugs under clinical trials in 2018. We have discussed various anticancer drugs in detail, their clinical studies, structure, and mechanism of action. The current review is an attempt to introduce clinical investigation of New Active Substance cancer therapeutics to the audience of this review and explores the pioneering anticancer drugs.