Sustainable Alternatives to Petroleum-Derived Excipients in Pharmaceutical Oil-in-Water Creams.

Recently, vast efforts towards sustainability have been made in the pharmaceutical industry. In conventional oil-in-water (O/W) cream formulations, various petroleum-based excipients, namely mineral oil and petrolatum, are commonly used. Natural or synthetic excipients, derived from vegetable sources, were explored as alternatives to petroleum-based excipients in prototype topical creams, with 1% (w/w) lidocaine. A conventional cream comprised of petroleum-derived excipients was compared to creams containing sustainable excipients in terms of key quality and performance attributes, physicochemical properties, and formulation performance. The petrolatum-based control formulation had the highest viscosity of 248.0 Pa·s, a melting point of 42.7°C, a low separation index at 25°C of 0.031, and an IVRT flux of 52.9 µg/cm2/h. Formulation SUS-4 was the least viscous formulation at 86.9 Pa·s, had the lowest melting point of 33.6°C, the highest separation index of 0.120, and the highest IVRT flux of 139.4 µg/cm2/h. Alternatively, SUS-5 had a higher viscosity of 131.3 Pa·s, a melting point of 43.6°C, a low separation index of 0.046, and the lowest IVRT flux of 25.2 µg/cm2/h. The cumulative drug permeation after 12 h from SUS-4, SUS-5, and the control were 126.2 µg/cm2, 113.8 µg/cm2, and 108.1 µg/cm2, respectively. The composition of the oil-in-water creams had influence on physicochemical properties and drug release; however, skin permeation was not impacted. Sustainable natural or synthetic excipients in topical cream formulations were found to be suitable alternatives to petroleum-based excipients with comparable key quality attributes and performance attributes and should be considered during formulation development.

A photothermal driven chemotherapy for the treatment of metastatic melanoma.

Solid tumors are abnormal mass of tissue, which affects the organs based on its malignancy and leads to the dysfunction of the affected organs. The major problem associated with treatment of solid tumors is delivering anticancer therapeutics to the deepest layers/core of the solid tumor. Deposition of excessive extracellular matrix (ECM) hinders the therapeutics to travel towards the core of the tumor. Therefore, conventional anticancer therapeutics can only reduce the tumor size and that also for a limited duration, and tumor recurrence occurs once the therapy is discontinued. Additionally, by the time the cancer is diagnosed, the cancer cells already started affecting the major organs of the body such as lung, liver, spleen, kidney, and brain, due to their ability to metastasize and lung is the primary site for them to be infiltrated. To facilitate the anticancer therapeutics to penetrate the deeper layers of tumor, and to provide concurrent treatment of both the solid tumor and metastasis, we have designed and developed a Bimodal Light Assisted Skin Tumor and Metastasis Treatment (BLAST), which is a combination of photothermal and chemotherapeutic moieties. The BLAST is composed of 2D boron nitride (BN) nanosheet with adsorbed molecules of BCL-2 inhibitor, Navitoclax (NAVI) on its surface, that can breakdown excessive ECM network and thereby facilitate dissociation of the solid tumor. The developed BLAST was evaluated for its ability to penetrate solid tumors using 3D spheroids for the uptake, cytotoxicity, growth inhibition, reactive oxygen species (ROS) detection, penetration, and downregulation of proteins upon laser irradiation. The in vivo therapeutic studies on a skin cancer mice model revealed that the BLAST with and without laser were able to penetrate the solid tumor, reduce tumor volume in mice, dissociate the protein network, and prevent lung metastasis as confirmed by immunohistochemistry and western blot analysis. Post analysis of serum and blood components revealed the safety and efficacy of BLAST in mice. Hence, the developed BLAST holds strong promise in solid tumor treatment and metastasis prevention simultaneously.

Potential and Progress of 2D Materials in Photomedicine for Cancer Treatment.

Over the last decades, photomedicine has made a significant impact and progress in treating superficial cancer. With tremendous efforts many of the technologies have entered clinical trials. Photothermal agents (PTAs) have been considered as emerging candidates for accelerating the outcome from photomedicine based cancer treatment. Besides various inorganic and organic candidates, 2D materials such as graphene, boron nitride, and molybdenum disulfide have shown significant potential for photothermal therapy (PTT). The properties such as high surface area to volume, biocompatibility, stability in physiological media, ease of synthesis and functionalization, and high photothermal conversion efficiency have made 2D nanomaterials wonderful candidates for PTT to treat cancer. The targeting or localized activation could be achieved when PTT is combined with chemotherapies, immunotherapies, or photodynamic therapy (PDT) to provide better outcomes with fewer side effects. Though significant development has been made in the field of phototherapeutic drugs, several challenges have restricted the use of PTT in clinical use and hence they have not yet been tested in large clinical trials. In this review, we attempted to discuss the progress, properties, applications, and challenges of 2D materials in the field of PTT and their application in photomedicine.

Application of carbon nano onions in the biomedical field: recent advances and challenges.

Carbon nano onions (CNOs) are carbonaceous nanostructures composed of multiple concentric shells of fullerenes. These cage-within-cage structures remain as one of the most exciting and fascinating carbon forms, along with graphene and its derivatives, due to their unique chemical and physical properties. Their exceptional biocompatibility and biosafety make them an attractive choice in a wide range of areas, including biological systems. This nanomaterial displays low toxicity, high dispersity in aqueous solutions (upon surface functionalization), and high pharmaceutical efficiency. Even though CNOs were discovered almost simultaneously along with carbon nanotubes (CNTs), their potential in biomedical applications still appears unrealized. The existence of CNOs is equally important, just like any other carbon nanostructures such as CNTs and fullerenes, because they display the ability of carbon to form another unique nanostructure with wonderful properties. Therefore, this mini-review summarizes recent studies geared towards developing CNOs for various biomedical applications, including sensing, drug delivery, imaging, tissue engineering, and as a therapeutic drug. It concludes by discussing other potential applications of this unique nanomaterial.

Physical triggering strategies for drug delivery.

Physically triggered systems hold promise for improving drug delivery by enhancing the controllability of drug accumulation and release, lowering non-specific toxicity, and facilitating clinical translation. Several external physical stimuli including ultrasound, light, electric fields and magnetic fields have been used to control drug delivery and they share some common features such as spatial targeting, spatiotemporal control, and minimal invasiveness. At the same time, they possess several distinctive features in terms of interactions with biological entities and/or the extent of stimulus response. Here, we review the key advances of such systems with a focus on discussing their physical mechanisms, the design rationales, and translational challenges.

Anticancer activity of Arkeshwara Rasa - A herbo-metallic preparation.

INTRODUCTION: Though metal based drugs have been prescribed in Ayurveda for centuries to treat various diseases, such as rheumatoid arthritis and cancer, toxicity of these drugs containing heavy metal is a great drawback for practical application. So, proper scientific validation of herbo-metallic drugs like Arkeshwara Rasa (AR) have become one of the focused research arena of new drugs against cancers. AIM: To investigate the in vitro anticancer effects of AR. MATERIALS AND METHODS: Anticancer activity of AR was investigated on two human cancer cell lines, which represent two different tissues (pancreas and skin). Lactate dehydrogenase (LDH) assay for enzyme activity and trypan blue assay for cell morphology were performed for further confirmation. RESULTS: AR showed potent activity against pancreatic cancer cells (MIA-PaCa-2). LDH activity confirmed that AR was active against pancreatic cancer cells. Finally, it was observed that AR exhibited significant effects on cancer cells due to synergistic effects of different compounds of AR. CONCLUSION: The study strongly suggests that AR has the potential to be an anticancer drug against pancreatic cancer.

Photoluminescent graphene nanoparticles for cancer phototherapy and imaging.

Graphene-based nanomaterials are of great interest in a wide range of applications in electronics, the environment, and energy as well as in biomedical and bioengineering. Their unique properties make them generally applicable as prognostic, diagnostic, and therapeutic agents in cancer. In this work, we focused on photodynamic and photothermal therapeutic properties of our previously synthesized carboxylated photoluminescent graphene nanodots (cGdots). The cGdots are ∼5 nm in diameter and excited at 655 nm. Our findings reveal that, upon laser irradiation by near-infrared (wavelength 670 nm) sensitizer, electrons of the cGdots starts to vibrate and form electron clouds, thereby generating sufficient heat (>50 °C) to kill the cancer cells by thermal ablation. The generation of singlet oxygen also occurs due to irradiation, thus acting similarly to pheophorbide-A, a well-known photodynamic therapeutic agent. The cGdots kills MDA-MB231 cancer cells (more than 70%) through both photodynamic and photothermal effects. The cGdots were equally effective in the in vivo model of MDA-MB231 xenografted tumor-bearing mice also as observed for 21 days. The cGdot was intravenously injected, and the tumor was irradiated by laser, resulting in final volume of tumor was ∼70% smaller than that of saline-treated tumor. It indicates that the growth rate of cGdot-treated tumor was slower compared to saline-treated tumor. The synthesized cGdots could enable visualization of tumor tissue in mice, thereby illustrating their use as optical imaging agents for detecting cancer noninvasively in deep tissue/organ. Collectively, our findings reveal that multimodal cGdots can be used for phototherapy, through photothermal or photodynamic effects, and for noninvasive optical imaging of deep tissues and tumors simultaneously.