Phytochemical Constituents and Derivatives of Cannabis sativa; Bridging the Gap in Melanoma Treatment.

Melanoma is deadly, physically impairing, and has ongoing treatment deficiencies. Current treatment regimens include surgery, targeted kinase inhibitors, immunotherapy, and combined approaches. Each of these treatments face pitfalls, with diminutive five-year survival in patients with advanced metastatic invasion of lymph and secondary organ tissues. Polyphenolic compounds, including cannabinoids, terpenoids, and flavonoids; both natural and synthetic, have emerging evidence of nutraceutical, cosmetic and pharmacological potential, including specific anti-cancer, anti-inflammatory, and palliative utility. Cannabis sativa is a wellspring of medicinal compounds whose direct and adjunctive application may offer considerable relief for melanoma suffers worldwide. This review aims to address the diverse applications of C. sativa's biocompounds in the scope of melanoma and suggest it as a strong candidate for ongoing pharmacological evaluation.

Manipulation of the Glass Transition Properties of a High-Solid System Made of Acrylic Acid-N,N'-Methylenebisacrylamide Copolymer Grafted on Hydroxypropyl Methyl Cellulose.

Crosslinking of hydroxypropyl methyl cellulose (HPMC) and acrylic acid (AAc) was carried out at various compositions to develop a high-solid matrix with variable glass transition properties. The matrix was synthesized by the copolymerisation of two monomers, AAc and N,N'-methylenebisacrylamide (MBA) and their grafting onto HMPC. Potassium persulfate (K2S2O8) was used to initiate the free radical polymerization reaction and tetramethylethylenediamine (TEMED) to accelerate radical polymerisation. Structural properties of the network were investigated with Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), modulated differential scanning calorimetry (MDSC), small-deformation dynamic oscillation in-shear, thermogravimetric analysis (TGA) and scanning electron microscopy (SEM). The results show the formation of a cohesive macromolecular entity that is highly amorphous. There is a considerable manipulation of the rheological and calorimetric glass transition temperatures as a function of the amount of added acrylic acid, which is followed upon heating by an extensive rubbery plateau. Complementary TGA work demonstrates that the initial composition of all the HPMC-AAc networks is maintained up to 200 °C, an outcome that bodes well for applications of targeted bioactive compound delivery.

Rationalizing a prospective coupling effect of cannabinoids with the current pharmacotherapy for melanoma treatment.

Melanoma is one of the leading fatal forms of cancer, yet from a treatment perspective, we have minimal control over its reoccurrence and resistance to current pharmacotherapies. The endocannabinoid system (ECS) has recently been accepted as a multifaceted homeostatic regulator, influencing various physiological processes across different biological compartments, including the skin. This review presents an overview of the pathophysiology of melanoma, current pharmacotherapy used for treatment, and the challenges associated with the different pharmacological approaches. Furthermore, it highlights the utility of cannabinoids as an additive remedy for melanoma by restoring the balance between downregulated immunomodulatory pathways and elevated inflammatory cytokines during chronic skin conditions as one of the suggested critical approaches in treating this immunogenic tumor. This article is categorized under: Cancer > Molecular and Cellular Physiology.

Evaluating the Mechanism of Cell Death in Melanoma Induced by the Cannabis Extract PHEC-66.

Research suggests the potential of using cannabinoid-derived compounds to function as anticancer agents against melanoma cells. Our recent study highlighted the remarkable in vitro anticancer effects of PHEC-66, an extract from Cannabis sativa, on the MM418-C1, MM329, and MM96L melanoma cell lines. However, the complete molecular mechanism behind this action remains to be elucidated. This study aims to unravel how PHEC-66 brings about its antiproliferative impact on these cell lines, utilising diverse techniques such as real-time polymerase chain reaction (qPCR), assays to assess the inhibition of CB1 and CB2 receptors, measurement of reactive oxygen species (ROS), apoptosis assays, and fluorescence-activated cell sorting (FACS) for apoptosis and cell cycle analysis. The outcomes obtained from this study suggest that PHEC-66 triggers apoptosis in these melanoma cell lines by increasing the expression of pro-apoptotic markers (BAX mRNA) while concurrently reducing the expression of anti-apoptotic markers (Bcl-2 mRNA). Additionally, PHEC-66 induces DNA fragmentation, halting cell progression at the G1 cell cycle checkpoint and substantially elevating intracellular ROS levels. These findings imply that PHEC-66 might have potential as an adjuvant therapy in the treatment of malignant melanoma. However, it is essential to conduct further preclinical investigations to delve deeper into its potential and efficacy.

Fundamental advances in hydrogels for the development of the next generation of smart delivery systems as biopharmaceuticals.

Recent advances in developing and applying therapeutic peptides for anticancer, antimicrobial and immunomodulatory remedies have opened a new era in therapeutics. This development has resulted in the engineering of new biologics as part of a concerted effort by the pharmaceutical industry. Many alternative routes of administration and delivery vehicles, targeting better patient compliance and optimal therapeutic bioavailability, have emerged. However, the design of drug delivery systems to protect a range of unstable macromolecules, including peptides and proteins, from high temperatures, acidic environments, and enzymatic degradation remains a priority. Herein, we give chronological insights in the development of controlled-release drug delivery systems that occurred in the last 70 years or so. Subsequently, we summarise the key physicochemical characteristics of hydrogels contributing to the development of protective delivery systems concerning drug-targeted delivery in the chronospatial domain for biopharmaceuticals. Furthermore, we shed some light on promising hydrogels that can be utilised for systemic bioactive administration.

In Vitro Antiproliferative Effect of Cannabis Extract PHEC-66 on Melanoma Cell Lines.

Melanoma, an aggressive form of skin cancer, can be fatal if not diagnosed and treated early. Melanoma is widely recognized to resist advanced cancer treatments, including immune checkpoint inhibitors, kinase inhibitors, and chemotherapy. Numerous studies have shown that various Cannabis sativa extracts exhibit potential anticancer effects against different types of tumours both in vitro and in vivo. This study is the first to report that PHEC-66, a Cannabis sativa extract, displays antiproliferative effects against MM418-C1, MM329 and MM96L melanoma cells. Although these findings suggest that PHEC-66 has promising potential as a pharmacotherapeutic agent for melanoma treatment, further research is necessary to evaluate its safety, efficacy, and clinical applications.

The Pathophysiology and the Therapeutic Potential of Cannabinoids in Prostate Cancer.

Prostate cancer is the second most frequently occurring cancer diagnosed among males. Recent preclinical evidence implicates cannabinoids as powerful regulators of cell growth and differentiation. In this review, we focused on studies that demonstrated anticancer effects of cannabinoids and their possible mechanisms of action in prostate cancer. Besides the palliative effects of cannabinoids, research from the past two decades has demonstrated their promising potential as antitumor agents in a wide variety of cancers. This analysis may provide pharmacological insights into the selection of specific cannabinoids for the development of antitumor drugs for the treatment of prostate cancer.

Fluorescent Magnesium Hydroxide Nanosheet Bandages with Tailored Properties for Biocompatible Antimicrobial Wound Dressings and pH Monitoring.

Magnesium hydroxide (Mg(OH)2) is hailed as a cheap and biocompatible material with antimicrobial potential; however, research aimed at instilling additional properties and functionality to this material is scarce. In this work, we synthesized novel, fluorescent magnesium hydroxide nanosheets (Mg(OH)2-NS) with a morphology that closely resembles that of graphene oxide. These multifunctional nanosheets were employed as a potent antimicrobial agent against several medically relevant bacterial and fungal species, particularly on solid surfaces. Their strong fluorescence signature correlates to their hydroxide makeup and can therefore be used to assess their degradation and functional antimicrobial capacity. Furthermore, their pH-responsive change in fluorescence can potentially act as a pH probe for wound acidification, which is characteristic of healthy wound healing. These fluorescent antimicrobial nanosheets were stably integrated into biocompatible electrospun fibers and agarose gels to add functionality to the material. This reinforces the suitability of the material to be used as antimicrobial bandages and gels. The biocompatibility of the Mg(OH)2-NS for topical medical applications was supported by its noncytotoxic action on human keratinocyte (HaCaT) cells.