Conventional chemotherapy for the treatment of cancer has limited specificity when administered systemically and is often associated with toxicity issues. Enhanced accumulation of polymeric nanocarriers at a tumor site may be achieved by passive and active targeting. Incorporation of trigger responsiveness into these polymeric nanocarriers improves the anticancer efficacy of such systems by modulating the release of the drug according to the tumor environment. Triggers used for tumor targeting include internal triggers such as pH, redox and enzymes and external triggers such as temperature, magnetic field, ultrasound and light. While internal triggers are specific cues of the tumor microenvironment, external triggers are those which are applied externally to control the release. This review highlights the various strategies employed for the preparation of such trigger responsive polymeric nanocarriers for cancer therapy and provides an overview of the state of the art in this field.

Chemotherapy is limited by the low availability of drug at the tumor site and drug resistance by the tumor. In this report we describe a combination therapy for codelivery of two anticancer drugs with spatiotemporal control by ultrasound pulses. We developed curcumin and topotecan-coencapsulated nanoconjugates Cur_Tpt_NC.MB to have an ultrasound contrast property. MDA MB 231 and B16F10 cells were incubated with Cur_Tpt_NC.MB and exposed to ultrasound. Ultrasound exposure reduced the IC 50 concentration of topotecan and curcumin significantly (P , 0.05) compared with free drug.Antitumor efficacy study of the Cur_Tpt_NC.MB in B16F10 melanoma tumor-bearing C57BL/6 mice showed that ultrasound exposure of right tumor reduced growth by 3.5 times compared with the unexposed left tumor of same mice and 14.8 times compared with a group treated with a physical mixture of drugs. These results suggest that the nanotherapeutic system we developed induces site-specific inhibition of tumor growth at a high rate and has the potential to be used as a therapeutic regimen for spatiotemporal delivery of dual drugs for treatment of cancer.

Systemic toxicity caused by conventional chemotherapy is often regarded as one of the major challenges in the treatment of cancer. Over years, the trigger-based modality has gained much attention as it holds the spatiotemporal control over release and internalization of the drug. In this article, we are reporting an increase in the anti-tumor efficacy of curcumin due to ultrasound pulses. MDA MB 231 breast cancer and B16F10 melanoma cells were incubated with lecithin-based curcumin encapsulated nanoemulsions and exposed to ultrasound in the presence and absence of microbubble. Ultrasound induced sonoporation enhanced the cytotoxicity of curcumin in MDA MB 231 and B16F10 cancer cells in the presence of microbubble by 100- and 64-fold, respectively. To study the spatiotemporal delivery of curcumin, we developed B16F10 melanoma subcutaneous tumor on both the flanks of C57BL/6 mice but only the right tumor was exposed to ultrasound. Insonation of the right tumor spatially enhanced the cytotoxicity and enabled the substantial regression of the right tumor compared to the unexposed left tumor which grew continuously in size. This study showed that the ultrasound has the potential to target and increase the drug’s throughput to the tumor and enable effective treatment.

The aim of the this study is to develop colon targeted drug delivery systems for Ibuprofen using grafted katira gum as a carrier. Polyacrylamide-grafted katira gum was synthesized by grafting acrylamide onto katira gum in presence of varying concentration of ceric ammonium nitrate (CAN) as initiator. Elemental analysis, FTIR, TGA, DTA, DSC, and SEM were used to characterize the grafting of acrylamide onto katira gum. Matrix tablets containing various proportions of grafted katira gum were prepared by wet granulation method. All the formulations were evaluated for hardness, drug content, swelling index, and in vitro release studies in simulated gastric fluid, small intestinal fluid, and simulated colonic fluid with and without enzymes. Ibuprofen was used for controlled release study. The drug release mechanism was studied by fitting into Peppas model and was found to be supercase-II transport. Matrix tablets containing 0.3 g of CAN/gm of acrylamide showed optimum value and retained its physical integrity in simulated gastric, small intestinal and colonic fluid, where as other composition disintegrated within 2 h of dissolution testing in pH 1.2 buffer, simulated gastric fluid. The results of this study indicates that Ibuprofen matrix tablet containing 60 wt % composition of the above grafted katira gum would be potential formulations in delivering the drug to the colon and the more susceptible for enzymatic degradation.

Prostaglandin E1, 4 microgram/min, infused locally intra-arterially (ia) for 60 minutes into forelimbs perfused at constant pump controlled inflow produced decreases in perfusion pressure, increases in lymph total protein concentration (approximately equal to g/100 ml), and small increases in weight (23 g) owing to edema formation. Histamine, 16 microgram base/min, or bradykinin, 10 microgram base/min, infused locally ia for 60 minutes produced large increases in lymph flow, lymph total protein concentration, total protein transport, and weight (70 g and 130 g, respectively). However, the local ia infusion of prostaglandin E1, 4 microgram/min, together with histamine, 16 microgram base/min, or bradykinin, 10 microgram base/min, produced weight increases of 180 g and 236 g, respectively, and the rate of weight gain during the combination infusions greatly exceeded that produced by infusions of histamine or bradykinin alone. Moreover, the increases in lymph flow and in total protein transport far exceeded those produced by infusions of prostaglandin E1 and histamine or bradykinin alone or additively. The edema produced by the local ia infusion of prostaglandin E1, 4 microgram/min, together with bradykinin, 10 microgram base/min, was even more more marked in naturally perfused forelimbs. Similarly, the local ia infusion of histamine, 4 microgram base/min, or bradykinin, 0.8 microgram base/min, for 60 minutes into forelimbs perfused at constant inflow produced increases in lymph flow, lymph total protein concentration, total protein transport, and weight (38 g and 14 g, respectively). In contrast, histamine, 4 microgram base/min, and bradykinin, 0.8 microgram base/min, infused together locally ia for 60 minutes produced increases in weight of 118 g. The increase in lymph flow and total protein transport was considerably more marked during the combined infusions than during the infusions of histamine or bradykinin alone or additively.