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.

Topical drug delivery by Sepineo P600 emulgel: Relationship between rheology, physical stability, and formulation performance.

The objective of this present work was to develop and optimize oil-in-water (O/W) emulsion-based gels, namely emulgels that allow maximum topical drug delivery while having desired microstructure and acceptable physical stability. Emulgels containing 2.0 wt% lidocaine were prepared using various concentrations (0.75-5.0 wt%) of Sepineo P600. Their droplet size distribution, physical stability, rheological behaviors, in vitro drug release, and skin permeation profiles were evaluated. Results show that the concentration of Sepineo P600 significantly influenced the microstructure, rheology, and physical stability of the emulgel formulations. The physico-chemical properties also reveals that at least 1.0 wt% Sepineo P600 was needed to produce stable emulgel formulations. All formulations exhibited non-Newtonian shear-thinning properties which are desirable for topical applications. Both the release and permeation rates decreased with increasing viscosity and rigidity of the formulation. The lower the complex modulus of the emulgels, the higher the steady-state flux of the drug through the skin. Adding Sepineo P600 to emulgel systems resulted in increased rheological properties, which in turn slowed the diffusion of the drug for in vitro release. Although as expected skin permeation was rate limiting since in vitro release was 3 to 4 log-fold faster than skin flux. However, an interesting finding was that the derived skin/vehicle partition coefficient suggested the ionic interaction between lidocaine and Sepineo polymer reducing the free drug, i.e., thermodynamic activity and hence the flux with increasing Sepineo P600 concentration. Overall, this study has provided us with valuable insights into understanding the relationship between the microstructure (rheology), physical stability and skin drug delivery properties which will help to design and optimize topical emulgel formulations.

Mucoadhesive Carrier-Mediated Oral Co-delivery of Bcl2 Inhibitors Improves Gastric Cancer Treatment.

Gastric cancer treatment is challenging due to the lack of early-stage diagnostic technology and targeted delivery systems. Currently, the available treatments for gastric cancer are surgery, chemotherapy, immunotherapy, and radiation. These strategies are either invasive or require systemic delivery, exerting toxicities within healthy tissues. By creation of a targeted delivery system to the stomach, gastric cancer can be treated in the early stages. Such an approach reduces the negative effects on the rest of the body by minimizing systemic absorbance and random localization. With this in mind, we developed a mucoadhesive vehicle composed of ß-Glucan And Docosahexaenoic Acid (GADA) for controlled drug/gene delivery. In the current study, we investigated the therapeutic effect of codelivery Bcl2 inhibitors navitoclax (NAVI) and siRNA (Bcl2) via oral using GADA. The therapeutic efficacy of the GADA-mediated oral NAVI/siRNA was investigated in a gastric cancer mouse model. Higher Bcl2 inhibition efficacy was observed in Western blotting and TUNEL assay in mice treated with GADA/NAVI/siRNA compared to free NAVI, siRNA, and NAVI/siRNA. Histology (H&E) and immunohistochemistry (Ki67, TUNEL, and BCl2) analyses confirmed a significant reduction of the tumor region. Interaction between GADA and mucus resulted in retention for over 6 h and thereby sustained local payload release. The developed oral carrier GADA is an emerging vehicle that has promising potential in oral delivery of both small and large molecules, and their mucoadhesive property results in improved therapeutic efficacy with minimal side effects compared to conventional treatment. This study opens a new window for the effective delivery of oral medicine for the treatment of gastric cancer and other gastrointestinal diseases.

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.

ß-Glucan-Mediated Oral Codelivery of 5FU and Bcl2 siRNA Attenuates Stomach Cancer.

Based on cancer-related deaths, stomach cancer is ranked fifth, and first among Hispanics. Lack of technologies for early diagnosis and unavailability of target-specific therapeutics are largely the causes of the poor therapeutic outcomes from existing chemotherapeutics. Currently available therapeutic modalities are invasive and require systemic delivery, although the cancer is localized in the stomach at its early stage. Therefore, we hypothesize that an oral local delivery approach can extend the retention duration of the therapeutics modalities within the stomach and thereby enhance therapeutic efficacy. To accomplish this, we have developed a ß-glucan (BG)-based oral delivery vehicle that can adhere to the mucus lining of the stomach for an extended period while controlling the release of Bcl2 siRNA and 5-fluorouracil (5FU) payload for over 6 h. We found that Bcl2 siRNA selectively knocked down the Bcl2 gene in a C57BL/6 stomach cancer mouse model followed by upregulation of apoptosis and remission of cancer. BG was found to be very effective in maintaining the stability of siRNA for at least 6 h, when submerged in simulated gastric juice tested in vitro. To investigate the potential therapeutic effects in vivo, we used a stomach cancer mouse model, where C57BL/6 mice were treated with 5FU, BG/5FU, siRNA, BG/siRNA, and BG/5FU/siRNA. Higher inhibition of Bcl2 and therapeutic efficacy were observed in mice treated with BG/5FU/siRNA confirmed with Western blotting and a TUNEL assay. Significant reduction in the tumor region was observed with histology (H&E) and immunohistochemistry (Ki67, TUNEL, and Bcl2) analyses. Overall, the oral formulation shows improved efficacy with nonsignificant side effects compared to the conventional treatment tested in the gastric cancer mouse model.