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Fulltext α-Mangostin Nanoparticles Cytotoxicity and Cell Death Modalities in Breast Cancer Cell Lines

Herdiana Y, Wathoni N, Shamsuddin S, Muchtaridi M

Molecules, 2021 Aug 24;26(17).
PMID: 34500560 DOI: 10.3390/molecules26175119

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.
Fulltext Drug release study of the chitosan-based nanoparticles

Herdiana Y, Wathoni N, Shamsuddin S, Muchtaridi M

Heliyon, 2022 Jan;8(1):e08674.
PMID: 35028457 DOI: 10.1016/j.heliyon.2021.e08674

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.
Fulltext Cytotoxicity Enhancement of α-Mangostin with Folate-Conjugated Chitosan Nanoparticles in MCF-7 Breast Cancer Cells

Herdiana Y, Wathoni N, Shamsuddin S, Muchtaridi M

Molecules, 2023 Nov 14;28(22).
PMID: 38005306 DOI: 10.3390/molecules28227585

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.
Fulltext Chitosan-Based Nano-Smart Drug Delivery System in Breast Cancer Therapy

Herdiana Y, Wathoni N, Gozali D, Shamsuddin S, Muchtaridi M

Pharmaceutics, 2023 Mar 08;15(3).
PMID: 36986740 DOI: 10.3390/pharmaceutics15030879

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.
Fulltext Chitosan-Based Nano Systems for Natural Antioxidants in Breast Cancer Therapy

Herdiana Y, Husni P, Nurhasanah S, Shamsuddin S, Wathoni N

Polymers (Basel), 2023 Jul 05;15(13).
PMID: 37447598 DOI: 10.3390/polym15132953

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.
Fulltext Towards halal pharmaceutical: Exploring alternatives to animal-based ingredients

Herdiana Y, Sofian FF, Shamsuddin S, Rusdiana T

Heliyon, 2024 Jan 15;10(1):e23624.
PMID: 38187251 DOI: 10.1016/j.heliyon.2023.e23624

Halal is a crucial concept for Muslim consumers regarding consumed products, including pharmaceutical ingredients, which are essential in modern medicine. To address the issue of using porcine-sourced ingredients in pharmaceuticals, it is essential to search for halal alternatives derived from poultry, animal by-products from meat processing, marine sources, and plants. However, the complexity of this problem is further compounded by the rapid advances in innovation and technology, which can lead to adulteration of ingredients derived from pigs. Other challenges include the sustainability of alternative materials, management of waste or by-products practice, halal awareness, certification, government policies, religious adherence of consumers, food suppliers, marketers, and purchasing of products. The importance of halal and non-halal problems, specifically in the context of pharmaceutical materials, is still rarely discussed, including alternatives derived from poultry, animal by-products, marine sources, and plants. Due to the increasing global population, there is a growing need to increase awareness and concern among Muslim consumers for halal products, including pharmaceuticals. Therefore, this research aimed to investigate the importance of halal and non-halal issues in pharmaceutical ingredients, the potential impact on the Muslim community, as well as opportunities and challenges in the search for alternative ingredients.
Fulltext Chitosan-Based Nanoparticles of Targeted Drug Delivery System in Breast Cancer Treatment

Herdiana Y, Wathoni N, Shamsuddin S, Joni IM, Muchtaridi M

Polymers (Basel), 2021 May 24;13(11).
PMID: 34074020 DOI: 10.3390/polym13111717

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.
Collagen-Based Nanoparticles as Drug Delivery System in Wound Healing Applications

Kusnadi K, Herdiana Y, Rochima E, Putra ON, Mohd Gazzali A, Muchtaridi M

Int J Nanomedicine, 2024;19:11321-11341.
PMID: 39524919 DOI: 10.2147/IJN.S485588

BACKGROUND: Conventional wound dressings often adhere to wounds and can cause secondary injury due to their lack of anti-inflammatory and antibacterial properties. In contrast, collagen-based nanoparticles (NPs) as drug delivery systems exhibit both biocompatibility and biodegradability, presenting a promising avenue for accelerating wound healing processes.
AIMS OF STUDY: This review aims to provide a comprehensive overview of the mechanisms involved in wound healing, description of the attributes of ideal wound dressings, understanding of wound healing efficacy of collagen, exploring NPs-mediated drug delivery mechanisms in wound therapy, detailing the synthesis and fabrication techniques of collagen-based NPs, and delineating the applications of various collagen-based NPs infused wound dressings on wound healing.
METHODOLOGY: This review synthesizes relevant literature from reputable databases such as Scopus, Science Direct, Google Scholar, and PubMed.
RESULTS: A diverse array of collagen-based NPs, including nanopolymers, metal NPs, nanoemulsions, nanoliposomes, and nanofibers, demonstrate pronounced efficacy in promoting wound closure and tissue regeneration. The incorporation of collagen-based NPs has not only become an agent for the delivery of therapeutics but also actively contributes to the wound healing cascade.
CONCLUSION: In conclusion, In brief, the use of collagen-based NPs presents a compelling strategy for expediting wound healing processes.
Fulltext Chitosan/Alginate Polymeric Nanoparticle-Loaded α-Mangostin: Characterization, Cytotoxicity, and In Vivo Evaluation against Breast Cancer Cells

Muchtaridi M, Suryani AI, Wathoni N, Herdiana Y, Mohammed AFA, Gazzali AM, et al.

Polymers (Basel), 2023 Sep 05;15(18).
PMID: 37765512 DOI: 10.3390/polym15183658

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.