Liposome-based diagnostic and therapeutic applications for pancreatic cancer.

Pancreatic cancer is one of the harshest and most challenging cancers to treat, often labeled as incurable. Chemotherapy continues to be the most popular treatment yet yields a very poor prognosis. The main barriers such as inefficient drug penetration and drug resistance, have led to the development of drug carrier systems. The benefits, ease of fabrication and modification of liposomes render them as ideal future drug delivery systems. This review delves into the versatility of liposomes to achieve various mechanisms of treatment for pancreatic cancer. Not only are there benefits of loading chemotherapy drugs and targeting agents onto liposomes, as well as mRNA combined therapy, but liposomes have also been exploited for immunotherapy and can be programmed to respond to photothermal therapy. Multifunctional liposomal formulations have demonstrated significant pre-clinical success. Functionalising drug-encapsulated liposomes has resulted in triggered drug release, specific targeting, and remodeling of the tumor environment. Suppressing tumor progression has been achieved, due to their ability to more efficiently and precisely deliver chemotherapy. Currently, no multifunctional surface-modified liposomes are clinically approved for pancreatic cancer thus we aim to shed light on the trials and tribulations and progress so far, with the hope for liposomal therapy in the future and improved patient outcomes. STATEMENT OF SIGNIFICANCE: Considering that conventional treatments for pancreatic cancer are highly associated with sub-optimal performance and systemic toxicity, the development of novel therapeutic strategies holds outmost relevance for pancreatic cancer management. Liposomes are being increasingly considered as promising nanocarriers for providing not only an early diagnosis but also effective, highly specific, and safer treatment, improving overall patient outcome. This manuscript is the first in the last 10 years that revises the advances in the application of liposome-based formulations in bioimaging, chemotherapy, phototherapy, immunotherapy, combination therapies, and emergent therapies for pancreatic cancer management. Prospective insights are provided regarding several advantages resulting from the use of liposome technology in precision strategies, fostering new ideas for next-generation diagnosis and targeted therapies of pancreatic cancer.

Plant-mediated green synthesis of metal-based nanoparticles for dermopharmaceutical and cosmetic applications.

The skin is the primordial barrier that protects the human body against environmental factors. Due to the arise of dermatological pathologies, the development of efficient delivery systems for topical applications has received increased interest. The highest challenge consists of increasing the penetration of the active ingredients through the skin barrier, alongside to the need of obtaining enough skin retention to achieve therapeutic concentrations. Metals, specially noble metals, have been used for years to treat and prevent health issues, among them dermatological disorders. Nanoparticles have been extensively used for topical applications given their advantages, namely by enhancing solubility of apolar drugs, the possibility of controlled release, the higher stability and the capability to target specific areas and delivery of high concentrations of active ingredients. In order to take advantage of the before mentioned unique properties of nanoparticles and the biological activities of metals, various metal-based nanoparticles (MNPs) have been synthesized in the past few years, such as silver (AgNPs), gold (AuNPs), zinc (ZnNPs), zinc oxide (ZnONPs), copper (CuNPs) and copper oxide (CuONPs) nanoparticles. These MNPs are flexible structures that allow the control of physical characteristics, with enhanced surface properties, which provides a high applicability in dermopharmacy and cosmetics. The conventional methods for synthesizing nanoparticles (physical and chemical approaches) are associated with major drawbacks, being the most concerning the high cost (in resources, energy, time and space) and human/environmental toxicity. Hence, the need to develop an alternative synthesis pathway was imposed, giving rise to the green synthesis methodology. In general, green synthesis consist of using biological sources (plants, bacteria or fungi) to synthesize ecological benign, non-hazard and biocompatible nanoparticles. With the development of green synthesis, starting materials have been used more frequently, among them plants. Plant-mediated green synthesis of nanoparticles is based on the use of plant extracts to synthesize nanoparticles, and their outstanding advantages have paved the way for exciting developments on nanoparticle synthesis to the detriment of complex and toxicity-associated chemical and physical synthesis. MNPs produced by plant-mediated synthesis also demonstrate notorious biological activities, i.e., anticancer, antioxidant, anti-inflammatory, antimicrobial, wound healing and antiaging activities. However, safety assessment of phyto MNPs (phyto-MNPs) holds significant importance due to the lack of toxicological studies and the conception issues that some of the available studies show. In general, current studies suggest the biocompatibility and safety of phyto-MNPs, together with significantly improved and relevant biological activities towards dermopharmaceutical and cosmetic applications. Against this backdrop, there is still a long way to run until the application of phyto-MNPs in the medical, pharmaceutical and cosmetic fields, but studies so far show a very high potential towards their clinical translation for dermopharmaceutical and cosmetics applications. This review focuses on phyto-MNPs synthesized resorting to various plant extracts, including their production, characterization and the biological activities that support their topical application for dermopharmaceutical and cosmetic purposes.

Cyclodextrin-based delivery systems for in vivo-tested anticancer therapies.

Cyclodextrins (CDs) are naturally occurring macromolecules widely used as excipients on pharmaceutical formulations, evidencing a large spectrum of applications in the pharmaceutical industry. Their unique ability to act as molecular containers by entrapping a wide range of guest molecules in their internal cavity makes them a remarkable excipient to improve drug apparent solubility, stability, and bioavailability, and a valuable tool for the assembly of new drug delivery systems. These features are especially useful when it comes to chemotherapy, as most of the anticancer drugs present both low permeability and reduced water solubility. Therefore, guest-host inclusion complexes offer several potential advantages not only regarding the improvement of pharmaceutical formulations characteristics but also considering the reduction of drug toxic side effects. The combination of CDs with additional technologies and materials constitutes a potential strategy towards the development of advanced and multifunctional CD-based delivery systems. Paclitaxel, curcumin, camptothecin, doxorubicin, and cisplatin are among the most studied molecules with anticancer activities and have been successfully incorporated in such nanosystems. Exciting results using CDs and CD-based delivery systems have been obtained so far, paving the way towards the attainment of intelligent delivery systems to possibly address cancer therapeutics' unmet needs. In this review, a comprehensive exposition concerning in vivo-tested CD and CD-based delivery systems for anticancer therapy is undertaken. Additionally, the authors address the multivalent functionalities of CD-based delivery systems, namely the incorporation of active target ligands, stimuli-responsiveness components, surface functionalization, or further associations with other delivery systems, aiming at improved in vivo anticancer therapies. Graphical abstract.