Current Drug Delivery - Volume 20, Issue 4, 2023

Breast cancer, being the second most common type of cancer, is a leading cause of death in the female population. Of all the available treatments existing for breast cancer, exosomes appear as an important medium for the site targeted delivery of the drugs. Exosomes, unlike all the other extracellular vesicles, play a vital role in the transport of numerous biomolecules throughout the body and can easily be detected because of the presence of specific biomarkers. Apart from playing a wide variety of roles in the progression of many diseases, they are also responsible for tumor progression and metastasis in breast cancer. Exosomes and related engineering strategies are being discussed as nano-carrier for the delivery of different drugs in the case of breast cancer. Overall, we have discussed in this review the role of exosomes in breast cancer and the engineering strategies being devised for making them an efficient drug delivery system.

On the one hand, oral formulations are susceptible to problems, including instability accompanied by erratic absorption throughout the gastrointestinal tract, first-pass metabolism, and patientrelated and pathological difficulties in consumption. On the other hand, the world has been observing a shift from conventional dermal formulations to the more cosmetically attractive ones. Amid all these, polymeric films and film-forming systems have emerged as promising candidates for addressing the above problems. Oral films have been studied for their potential applications in immediate and sustained- release formulations and have markedly shown increased plasma concentrations of drugs that otherwise undergo degradation in the gastrointestinal tract and the liver and have an obvious edge in treating pathologies of the oral cavity. At the same time, a variety of dermal film formulations have been developed and studied for treating wounds, skin infections and pathologies, corns and calluses, and managing pain. This review article attempts to cover significant findings in oral and dermal applications of these formulations under one umbrella and provide readers with a compilation of relevant research works and marketed formulations.

Cancer immunotherapy has advanced significantly in recent years. Nanocarriers like liposomes can improve cancer immunotherapy and even stronger immune responses by improving cell type-specific distribution. Liposomes are lipid bilayer vesicles that are biodegradable and biocompatible and are often used as smart delivery systems for both hydrophobic and hydrophilic bioactive. Whereas the idea of employing liposomes for administering drugs has been known since the 1960s, the early 2000s saw continuing technological advances and formulations for drug entrapment and manufacturing. Modern deterministic studies have tried discovering more about how genetic material is delivered through liposomes. Liposomes' interactions with cells are still a bit of mystery. Liposome-mediated transmission of genetic material experiences systemic impediments perlysosomal degradation, endosomal escape, and nuclear uptake. Controlling the physical architecture and chemical properties of liposome structures, such as lipid-to-DNA charge, ester bond composition, size, and ligand complexation structure, is critical for targeting liposomes' success as vehicles for gene delivery. This analysis focuses on advancements in ligand-targeted liposomes and theranostic (diagnostic) liposomes for cancer diagnosis and treatment. This review will explore the numerous transgene mechanisms and molecular targets implicated in cancer cell death and the associated benefits of using liposomal formulations throughout the years. This sequence of breakthroughs will interest aspiring researchers and the pharmaceutical industry involved in liposome development.

Background: Cancer, an uncontrolled multistage disease causing swift division of cells, is a leading disease with the highest mortality rate. Cellular heterogeneity, evading growth suppressors, resisting cell death, and replicative immortality drive the tumor progression by resisting the therapeutic action of existing anticancer drugs through a series of intrinsic and extrinsic cellular interactions. The innate cellular mechanisms also regulate the replication process as a fence against proliferative signaling, enabling replicative immortality through telomere dysfunction. Area Covered: The conventional genotoxic drugs have several off-target and collateral side effects associated with them. Thus, the need for the therapies targeting cyclin-dependent kinases or P13K signaling pathway to expose cancer cells to immune destruction, deactivation of invasion and metastasis, and maintaining cellular energetics is imperative. Compounds with anticancer attributes isolated from plants and rich in alkaloids, terpenes, and polyphenols have proven to be less toxic and highly targetspecific, making them biologically significant. This has opened a gateway for the exploration of more novel plant molecules by signifying their role as anticancer agents in synergy and alone, making them more effective than the existing cytotoxic regimens. Expert Opinion: In this context, the current review presented recent data on cancer cases around the globe, along with discussing the fundamentals of proliferative signaling and replicative immortality of cancer cells. Recent findings were also highlighted, including antiproliferative and antireplicative action of plant-derived compounds, besides explaining the need for improving drug delivery systems.

Background: 5-azacitidine is a very potent chemotherapeutic agent that suffers from certain disadvantages. Objective: This study aims to prepare gold nanoparticles as a new nano-formula of 5-azacitidine that can improve its bioavailability and decrease its side effects. Methods: 5-azacytidine-loaded GA-AuNPs were prepared and characterized by UV-Vis spectroscopy, infrared (IR), and electronic transmission microscope (TEM). This new platform was characterized in vitro by measuring its zeta potential, particle size, and drug loading efficacy, and the anti-proliferative effect on the MCF-7 cell line was evaluated. In vivo biodistribution studies of ^99mTc-5-aza solution and ^99mTc-5-aza-gold nano formula were conducted in tumor-bearing mice by different routes of administration (intravenous and intra-tumor). Results: 5-Aza-GA-AuNPs formula was successfully prepared with an optimum particle size of ≈34.66 nm, the zeta potential of -14.4 mV, and high entrapment efficiency. ^99mTc-5-Aza-GA-AuNPs were successfully radiosynthesized with a labeling yield of 95.4%. Biodistribution studies showed high selective accumulation in tumor and low uptake in non-target organs in the case of the 5-Aza-GA-AuNPs formula than the ^99mTc-5-azacitidine solution. Conclusion: ^99mTc-5-Aza-GA-AuNPs improved the selectivity and uptake of 5-azacitidine in cancer. Moreover, ^99mTc-5-Aza-GA-AuNPs could be used as hopeful theranostic radiopharmaceutical preparation for cancer.

Background: Wound healing is one of the major challenges in chronic diseases; the current treatment options are less effective with undesirable side effects and are expensive. Extensive research is carried out to develop cost-effective, natural, biodegradable wound dressings that can reduce oxidative stress and inflammation and prevent bacterial infections. Curcumin has a plethora of therapeutic applications; however, its low solubility limits its clinical use. Objective: In this study, curcumin nanoparticles (Cur NP) and curcumin-chitosan nanoparticles (CCNP) were incorporated into the chitosan collagen vanillin scaffold, characterized, and investigated their potential wound healing properties. Methods: The nano-scaffolds were prepared by freeze-drying method and were characterized using Fourier transform infrared spectroscopy, X-ray diffraction, nanoparticle tracking analysis, and scanning electron microscopy. The drug release, antioxidant, antibacterial, and wound healing properties were assessed by in vitro assays. Results: Cur nano-scaffolds showed particle sizes of 195.9 nm and 110.6 nm for Cur NP+VC and CCNP+VC, respectively. The curcumin encapsulated in the Cur NP+VC and CC+VC nano-scaffolds showed a release profile of > 60% and an improved antioxidant activity of greater than 80%. The nanoscaffolds were antagonistic against Escherichia coli and Staphylococcus aureus and enhanced wound healing capacity of 85.62 % and 77.05% in the murine cell line. Conclusion: The curcumin nano-scaffold is a biodegradable and effective drug delivery system for topical use that can act as an antioxidant, facilitate wound healing, as well as prevent bacterial infections.

Purpose: To formulate and characterize tablets containing Pitavastatin that have been loaded with a self-nano emulsifying drug delivery system (SNEDDS). Methods: Pitavastatin SNEDDS were prepared with a variety of oils, surfactants, co-surfactants, and solvents to improve the dissolution rate and bioavailability of the HMG-CoA reductase inhibitor. The SNEDDS components were preliminarily investigated for drug solubility in various vehicles, excipient miscibility, emulsification rate, and ternary phase diagrams. The tablets were made using a porous carrier made of Aerosil 200 and then loaded with SNEDDS using a simple absorption method. Physical parameters such as tablet hardness, weight variation, disintegration, drug content, and in-vitro drug release were then measured on the tablets. Results: Labrafac Lipophilewl1349 (Oil), Tween 80 (Surfactant) and Egg lecithin (Co-surfactant) were selected for the preparation of SNEDDS. Tablets with high porosity suitable for loading with SNEDDS and containing the super-disintegrants, achieved complete dissolution of Pitavastatin from the tablets. In vitro release of Pitavastatin from SNEDDS and the tablets was similar (p < 0.05). Conclusion: SNEDDS of Pitavastatin is a promising approach to achieving a solid dosage form of the liquid-loaded drug delivery systems for enhancing the solubility and dissolution rate of the drug, and hence also its bioavailability.

Objective: In order to overcome the insolution and low bioavailability of the vitexin in vivo, β-cyclodextrin-vitexin (β-CD-vitexin) microspheres were prepared, and their effects on the proliferation of SW480 cells were observed. Methods: Scanning electron microscopy, ultraviolet spectrum, Fourier transform infrared spectroscopy, and release rate analysis identified the formation of β-CD-vitexin microspheres. MTT assay detected the effect of β-CD-vitexin microspheres on tumor cell proliferation at 6, 12, 24, and 48 h. Fluorescence microscopy and flow cytometry were used to observe the effect of β-CD-vitexin microspheres on the apoptosis of SW480 cells. The mRNA expression of the p53 gene was measured by qPCR. Results: β-CD-vitexin microspheres were successfully prepared. SW480 cell proliferation was inhibited by 0.1, 0.2, and 0.4 mg/mL of β-CD-vitexin microspheres in a dose- and time-dependent manner, and the mechanism of proliferation inhibition was related to cell apoptosis caused by the upregulated expression of p53 gene. Conclusion: The preparation of β-CD-vitexin sustained release microspheres is feasible, and β-CDvitexin microspheres have potential anti-colorectal cancer value.