α-Mangostin (AMG) is a potent anticancer xanthone that was discovered in mangosteen (Garcinia mangostana Linn.). AMG possesses the highest opportunity for chemopreventive and chemotherapeutic therapy. AMG inhibits every step in the process of carcinogenesis. AMG suppressed multiple breast cancer (BC) cell proliferation and apoptosis by decreasing the creation of cancerous compounds. Accumulating BC abnormalities and their associated molecular signaling pathways promotes novel treatment strategies. Chemotherapy is a commonly used treatment; due to the possibility of unpleasant side effects and multidrug resistance, there has been substantial progress in searching for alternative solutions, including the use of plant-derived natural chemicals. Due to the limitations of conventional cancer therapy, nanotechnology provides hope for effective and efficient cancer diagnosis and treatment. Nanotechnology enables the delivery of nanoparticles and increased solubility of drugs and drug targeting, resulting in increased cytotoxicity and cell death during BC treatment. This review summarizes the progress and development of AMG's cytotoxicity and the mechanism of death BC cells. The combination of natural medicine and nanotechnology into a synergistic capital will provide various benefits. This information will aid in the development of AMG nanoparticle preparations and may open up new avenues for discovering an effective BC treatment.
Recently, multifunctional drug delivery systems (DDSs) have been designed to provide a comprehensive approach with multiple functionalities, including diagnostic imaging, targeted drug delivery, and controlled drug release. Chitosan-based drug nanoparticles (CSNPs) systems are employed as diagnostic imaging and delivering the drug to particular targeted sites in a regulated manner. Drug release is an important factor in ensuring high reproducibility, stability, quality control of CSNPs, and scientific-based for developing CSNPs. Several factors influence drug release from CSNPs, including composition, composition ratio, ingredient interactions, and preparation methods. Early, CSNPs were used for improving drug solubility, stability, pharmacokinetics, and pharmacotherapeutics properties. Chitosan has been developed toward a multifunctional drug delivery system by exploring positively charged properties and modifiable functional groups. Various modifications to the polymer backbone, charge, or functional groups will undoubtedly affect the drug release from CSNPs. The drug release from CSNPs has a significant influence on its therapeutic actions. Our review's objective was to summarize and discuss the relationship between the modification in CSNPs as multifunctional delivery systems and drug release properties and kinetics of the drug release model. Kinetic models help describe the release rate, leading to increased efficiency, accuracy, the safety of the dose, optimizing the drug delivery device's design, evaluating the drug release rate, and improvement of patient compatibility. In conclusion, almost all CSNPs showed bi-phasic release, initial burst release drug in a particular time followed controlled manner release in achieving the expected release, stimuli external can be applied. CSNPs are a promising technique for multifunctional drug delivery systems.
α-mangostin (AM) is a promising natural anticancer agent that can be used in cancer research. However, its effectiveness can be limited by poor solubility and bioavailability. To address this issue, chitosan-based nanoparticles (CSNPs) have been investigated as a potential delivery system to enhance the cytotoxicity to cancer cells and improve selectivity against normal cells. In this study, we developed folate-conjugated chitosan nanoparticles (F-CS-NPs) using a carbodiimide-based conjugation method to attach folate to chitosan (CS), which have different molecular weights. The NPs were crosslinked using tripolyphosphate (TPP) via ionic gelation. To characterize the F-CS-NPs, we utilized various analytical techniques, including transmission electron microscopy (TEM) to evaluate the particle size and morphology, Fourier-transform infrared spectroscopy (FTIR) to confirm the presence of functional groups, and ultraviolet-visible spectroscopy (UV-Vis) to measure the absorption spectrum and confirm the presence of folate. The particle size of AM-F-CS-NPs ranged from 180 nm to 250 nm, with many having favorable charges ranging from +40.33 ± 3.4 to 10.69 ± 1.3 mV. All NPs exhibited the same spherical morphology. The use of F-CS-NPs increased drug release, followed by a sustained release pattern. We evaluated the cytotoxicity of AM, AM-F-CS-HMW, and AM-F-CS-LMW NPs against MCF-7 cells and found IC50 values of 8.47 ± 0.49, 5.3 ± 0.01, and 4.70 ± 0.11 µg/mL, respectively. These results confirm the improved cytotoxicity of AM in MCF-7 cells when delivered via F-CS-NPs. Overall, our in vitro study demonstrated that the properties of F-CS-NPs greatly influence the cytotoxicity of AM in MCF-7 breast cancer cells (significantly different (p < 0.05)). The use of F-CS-NPs as a drug-delivery system for AM may have the potential to develop novel therapies for breast cancer.
Despite recent advances, cancer remains the primary killer on a global scale. Numerous forms of research have been conducted to discover novel and efficient anticancer medications. The complexity of breast cancer is a major challenge which is coupled with patient-to-patient variations and heterogeneity between cells within the tumor. Revolutionary drug delivery is expected to provide a solution to that challenge. Chitosan nanoparticles (CSNPs) have prospects as a revolutionary delivery system capable of enhancing anticancer drug activity and reducing negative impacts on normal cells. The use of smart drug delivery systems (SDDs) as delivering materials to improve the bioactivity of NPs and to understand the intricacies of breast cancer has garnered significant interest. There are many reviews about CSNPs that present various points of view, but they have not yet described a series in cancer therapy from cell uptake to cell death. With this description, we will provide a more complete picture for designing preparations for SDDs. This review describes CSNPs as SDDSs, enhancing cancer therapy targeting and stimulus response using their anticancer mechanism. Multimodal chitosan SDDs as targeting and stimulus response medication delivery will improve therapeutic results.
Breast cancer is a major cause of death globally, accounting for around 13% of all deaths. Chemotherapy, the common treatment for cancer, can have side effects that lead to the production of reactive oxygen species (ROS) and an increase in oxidative stress in the body. Antioxidants are important for maintaining the health of cells and helping the immune system function properly. They play a crucial role in balancing the body's internal environment. Using natural antioxidants is an alternative to mitigate the harmful effects of oxidative stress. However, around 80% of natural antioxidants have limited effectiveness when taken orally because they do not dissolve well in water or other solvents. This poor solubility affects their ability to be absorbed by the body and limits their bioavailability. One strategy that has been considered is to increase their water solubility to increase their oral bioavailability. Chitosan-based nanoparticle (CSNP) systems have been extensively explored due to their reliability and simpler synthesis routes. This review focuses on the various methods of chitosan-based nanoformulation for developing effective oral dosage forms for natural antioxidants based on the pharmacokinetics and pharmacodynamics properties. Chitosan (CS) could be a model, because of its wide use in polymeric NPs research, thus providing a better understanding of the role of vehicles that carry natural antioxidants in maintaining the stability and enhancing the performance of cancer drugs.
Breast cancer remains one of the world's most dangerous diseases because of the difficulty of finding cost-effective and specific targets for effective and efficient treatment methods. The biodegradability and biocompatibility properties of chitosan-based nanoparticles (ChNPs) have good prospects for targeted drug delivery systems. ChNPs can transfer various antitumor drugs to targeted sites via passive and active targeting pathways. The modification of ChNPs has attracted the researcher to the loading of drugs to targeted cancer cells. The objective of our review was to summarize and discuss the modification in ChNPs in delivering anticancer drugs against breast cancer cells from published papers recorded in Scopus, PubMed, and Google Scholar. In order to improve cellular uptake, drug accumulation, cytotoxicity, and selectivity, we examined different kinds of modification of ChNPs. Notably, these forms of ChNPs use the characteristics of the enhanced permeability and retention (EPR) effect as a proper parameter and different biological ligands, such as proteins, peptides, monoclonal antibodies, and small particles. In addition, as a targeted delivery system, ChNPs provided and significantly improved the delivery of drugs into specific breast cancer cells (MDA-MB-231, 4T1 cells, SK-BR-3, MCF-7, T47D). In conclusion, a promising technique is presented for increasing the efficacy, selectivity, and effectiveness of candidate drug carriers in the treatment of breast cancer.
Recurrent aphthous stomatitis (RAS) refers to a sore and frequently recurring inflammation of the oral tissues, distinguished by the presence of small ulcers that cause significant discomfort and cannot be attributed to any underlying disease. Different treatments have been used for RAS. This review aims to provide a comprehensive overview of the treatment options over the past decade for recurrent aphthous stomatitis (RAS), encompassing both natural and synthetic treatments. It will utilize clinical efficacy studies conducted in vivo and in vitro, along with a focus on the pharmaceutical approach through advancements in drug delivery development. We conducted a thorough literature search from 2013 to 2023 in prominent databases such as PubMed, Scopus, and Cochrane, utilizing appropriate keywords of recurrent aphthous stomatitis, and treatment. A total of 53 clinical trials with 3022 patients were included, with 35 using natural materials in their research and a total of 16 articles discussing RAS treatment using synthetic materials. All the clinical trials showed that natural and synthetic medicines seemed to benefit RAS patients by reducing pain score, ulcer size, and number of ulcers and shortening the healing duration.
α-mangostin (Amg), a compound isolated from the mangosteen rind (Garcinia mangostana, L.), has demonstrated promising anticancer activity. However, its low solubility and selectivity against cancer cells limit its efficacy. To address this issue, researchers have developed chitosan/alginate polymeric nanoparticles (NANO-AMCAL) to enhance the effectiveness of Amg. In vitro studies have demonstrated that NANO-AMCAL is highly active against breast cancer cells. Therefore, an in vivo study was conducted to evaluate the efficacy of NANO-AMCAL in treating breast cancer in Wistar rats (Rattus norvegicus) and determine the effective dose. The rats were divided into seven treatment groups, including positive control, negative control, pure Amg, and NANO-AMCAL 5 mg, 10 mg, and 20 mg. The rats were injected subcutaneously with a carcinogenic agent, 7,12-dimethylbenz(a)anthracene (DMBA) and were evaluated for weight and tumor volume every three days during treatment. Surgery was performed on day 14, and histopathological studies were carried out on breast and lung cancer tissues. The results showed that NANO-AMCAL significantly enhanced the anticancer activity of Amg in treating breast cancer in Wistar rats. NANO-AMCAL containing 0.33 mg of Amg had a healing effect three times better than 20 mg pure Amg and was comparable to tamoxifen. The effective dose of NANO-AMCAL for anti-breast cancer treatment in Wistar rats was found to be 20 mg, which exhibited a good healing response, and the tumor volume continued to decrease up to 17.43% on the 14th day. Furthermore, histopathological tests showed tissue repair and no metastases. These findings suggest that NANO-AMCAL may be a promising therapeutic option for breast cancer treatment.
Background: Recurrent Aphthous Stomatitis (RAS) is a common ulcerative disease of the oral mucosa which is characterized by pain, and recurrent lesions in the oral cavity. This condition is quite painful, causing difficulty in eating, speaking and swallowing. Topical medications have been used for this condition, but the obstacle in using topical medications is the difficulty of achieving drug effects due to saliva wash out. This problem can be overcome by film hydrogel formulation which can protect the ulcer and reduce the pain to some extent. α-mangostin is a xanthone isolated from the rind of the mangosteen fruit. One of the activities of α-mangostin is anti-inflammatory effects, which operate through the characteristic mechanism of inhibiting the inflammatory response. This protocol study aims to investigate the efficacy of an α-mangostin hydrogel film with a chitosan alginate base for recurrent aphthous stomatitis (RAS) in comparison with a placebo over a period of 7 days. Study design: This is a two-arm, double blinding, randomized controlled trial enrolling patients with RAS. The efficacy test of α-mangostin Hydrogel Film will be tested against the placebo. Patients with RAS will be allocated randomly into the two arms and the hydrogel film will be administered for 7 days. The diameter of ulcer and visual analog scale (VAS) score will be used as the primary efficacy endpoint. The outcome measure will be compared between the two arms at the baseline, day 3, day 5, and at the end of 7 days. Discussion: The purpose of this clinical research is to provide scientific evidence on the efficacy of α-mangostin hydrogel film with a chitosan alginate basis in treating recurrent aphthous stomatitis. The trial is expected to improve our capacity to scientifically confirm the anti-inflammatory effectiveness of α-mangostin compounds in a final formulation that is ready to use. Trial registration: NCT06039774 (14 September 2023).