Characterization and efficacy of C60 nano-photosensitive drugs in colorectal cancer treatment.

BACKGROUND: Fullerenes C60 shows great potential for drug transport. C60 generates large amounts of singlet oxygen upon photoexcitation, which has a significant inhibitory effect on tumor cells, so the photosensitive properties of C60 were exploited for photodynamic therapy of tumors by laser irradiation. METHODS: In this study, C60-NH2 was functionalized by introducing amino acids on the surface of C60, coupled with 5-FU to obtain C60 amino acid-derived drugs (C60AF, C60GF, C60LF), and activated photosensitive drugs (C60AFL, C60GFL, C60LFL) were obtained by laser irradiation. The C60 nano-photosensitive drugs were characterized in various ways, and the efficacy and safety of C60 nano-photosensitive drugs were verified by cellular experiments and animal experiments. Bioinformatics methods and cellular experiments were used to confirm the photosensitive drug targets and verify the therapeutic targets with C60AF. RESULTS: Photosensitised tumor-targeted drug delivery effectively crosses cell membranes, leads to more apoptotic cell death, and provides higher anti-tumor efficacy and safety in vitro and in vivo colorectal cancer pharmacodynamic assays compared to free 5-FU.C60 photosensitized drug promotes tumor killing by inhibiting the colorectal cancer FLOR1 tumor protein target, with no significant toxic effects on normal organs. CONCLUSION: C60 photosensitized drug delivery systems are expected to improve efficacy and reduce side effects in the future treatment of colorectal cancer. Further and better development and design of drugs and vectors for colorectal cancer therapy.

Self-Assembling Drug Formulations with Tunable Permeability and Biodegradability.

This review focuses on key topics in the field of drug delivery related to the design of nanocarriers answering the biomedicine criteria, including biocompatibility, biodegradability, low toxicity, and the ability to overcome biological barriers. For these reasons, much attention is paid to the amphiphile-based carriers composed of natural building blocks, lipids, and their structural analogues and synthetic surfactants that are capable of self-assembly with the formation of a variety of supramolecular aggregates. The latter are dynamic structures that can be used as nanocontainers for hydrophobic drugs to increase their solubility and bioavailability. In this section, biodegradable cationic surfactants bearing cleavable fragments are discussed, with ester- and carbamate-containing analogs, as well as amino acid derivatives received special attention. Drug delivery through the biological barriers is a challenging task, which is highlighted by the example of transdermal method of drug administration. In this paper, nonionic surfactants are primarily discussed, including their application for the fabrication of nanocarriers, their surfactant-skin interactions, the mechanisms of modulating their permeability, and the factors controlling drug encapsulation, release, and targeted delivery. Different types of nanocarriers are covered, including niosomes, transfersomes, invasomes and chitosomes, with their morphological specificity, beneficial characteristics and limitations discussed.

Ophthalmic Nanoemulsions: From Composition to Technological Processes and Quality Control.

Nanoemulsions are considered as the most promising solution to improve the delivery of ophthalmic drugs. The design of ophthalmic nanoemulsions requires an extensive understanding of pharmaceutical as well as technological aspects related to the selection of excipients and formulation processes. This Review aims at providing the readers with a comprehensive summary of possible compositions of nanoemulsions, methods for their formulation (both laboratory and industrial), and differences between technological approaches, along with an extensive outline of the research methods enabling the confirmation of in vitro properties, pharmaceutical performance, and biological activity of the obtained product. The composition of the formulation has a major influence on the properties of the final product obtained with low-energy emulsification methods. Increasing interest in high-energy emulsification methods is a consequence of their scalability important from the industrial perspective. Considering the high-energy emulsification methods, both the composition and conditions of the process (e.g., device power level, pressure, temperature, homogenization time, or number of cycles) are important for the properties and stability of nanoemulsions. It is advisible to determine the effect of each parameter on the quality of the product to establish the optimal process parameters' range which, in turn, results in a more reproducible and efficient production.

Marine Polysaccharides as a Versatile Biomass for the Construction of Nano Drug Delivery Systems.

Marine biomass is a treasure trove of materials. Marine polysaccharides have the characteristics of biocompatibility, biodegradability, non-toxicity, low cost, and abundance. An enormous variety of polysaccharides can be extracted from marine organisms such as algae, crustaceans, and microorganisms. The most studied marine polysaccharides include chitin, chitosan, alginates, hyaluronic acid, fucoidan, carrageenan, agarose, and Ulva. Marine polysaccharides have a wide range of applications in the field of biomedical materials, such as drug delivery, tissue engineering, wound dressings, and sensors. The drug delivery system (DDS) can comprehensively control the distribution of drugs in the organism in space, time, and dosage, thereby increasing the utilization efficiency of drugs, reducing costs, and reducing toxic side effects. The nano-drug delivery system (NDDS), due to its small size, can function at the subcellular level in vivo. The marine polysaccharide-based DDS combines the advantages of polysaccharide materials and nanotechnology, and is suitable as a carrier for different pharmaceutical preparations. This review summarizes the advantages and drawbacks of using marine polysaccharides to construct the NDDS and describes the preparation methods and modification strategies of marine polysaccharide-based nanocarriers.

Facial Solid-Phase Synthesis of Well-Defined Zwitterionic Amphiphiles for Enhanced Anticancer Drug Delivery.

Serum protein adsorption on the nanoparticle surface determines the biological identity of polymeric nanocarriers and critically impacts the in vivo stability following intravenous injection. Ultrahydrophilic surfaces are desired in delivery systems to reduce the serum protein corona formation, prolong drug pharmacokinetics, and improve the in vivo performance of nanotherapeutics. Zwitterionic polymers have been explored as alternative stealth materials for biomedical applications. In this study, we employed facial solid-phase peptide chemistry (SPPC) to synthesize multifunctional zwitterionic amphiphiles for application as a drug delivery vehicle. SPPC facilitates synthesis and purification of the well-defined dendritic amphiphiles, yielding high-purity and precise architecture. Zwitterionic glycerylphosphorylcholine (GPC) was selected as a surface moiety for the construction of a ultrahydrophilic dendron, which was coupled on solid phase to a hydrophobic dendron using multiple rhein (Rh) molecules as drug-binding moieties (DBMs) for doxorubicin (DOX) loading via pi-pi stacking and hydrogen bonding. The resulting zwitterionic amphiphilic Janus dendrimer (denoted as GPC8-Rh4) showed improved stabilities and sustained drug release compared to the analogue with poly(ethylene glycol) (PEG) surface (PEG5k-Rh4). In vivo studies in xenograft mouse tumor models demonstrated that the DOX-GPC8-Rh4 nanoformulation significantly improved anticancer effects compared to DOX-PEG5k-Rh4, owing to the improved in vivo pharmacokinetics and increased tumor accumulation.