ABSTRACT
OBJECTIVE: This study aims to utilize PEGylated poly (lactic-co-glycolic acid) (PLGA) nanoparticles as a delivery system for simultaneous administration of the BRAFV600E peptide, a tumor-specific antigen, and imiquimod (IMQ). The objective is to stimulate dendritic cell (DC) maturation, activate macrophages, and facilitate antigen presentation in C57BL6 mice. METHODS: PEG-PLGA-IMQ-BRAFV600E nanoparticles were synthesized using a PLGA-PEG-PLGA tri-block copolymer, BRAFV600E, and IMQ. Characterization included size measurement and drug release profiling. Efficacy was assessed in inhibiting BPD6 melanoma cell growth and activating immature bone marrow DCs, T cells, macrophages, and splenocyte cells through MTT and ELISA assays. In vivo, therapeutic and immunogenic effects potential was evaluated, comparing it to IMQ + BRAFV600E and PLGA-IMQ-BRAFV600E nanoparticles in inhibiting subcutaneous BPD6 tumor growth. RESULTS: The results highlight the successful synthesis of PEG-PLGA-IMQ-BRAFV600E nanoparticles (203 ± 11.1 nm), releasing 73.4% and 63.2% of IMQ and BARFV600E, respectively, within the initial 48 h. In vitro, these nanoparticles demonstrated a 1.3-fold increase in potency against BPD6 cells, achieving ~ 2.8-fold enhanced cytotoxicity compared to PLGA-IMQ-BRAFV600E. Moreover, PEG-PLGA-IMQ-BRAFV600E exhibited a 1.3-fold increase in potency for enhancing IMQ cytotoxic effects and a 1.1- to ~ 2.4-fold increase in activating DCs, T cells, macrophages, and splenocyte cells compared to IMQ-BRAFV600E and PLGA-IMQ-BRAFV600E. In vivo, PEG-PLGA-IMQ-BRAFV600E displayed a 1.3- to 7.5-fold increase in potency for inhibiting subcutaneous BPD6 tumor growth compared to the other formulations. CONCLUSIONS: The findings suggest that PEG-PLGA nanoparticles effectively promote DC maturation, T cell activation, and potentially macrophage activation. The study highlights the promising role of this nanocomposite in vaccine development.
Subject(s)
Dendritic Cells , Imiquimod , Melanoma , Mice, Inbred C57BL , Nanoparticles , Polyethylene Glycols , Proto-Oncogene Proteins B-raf , Animals , Dendritic Cells/immunology , Dendritic Cells/drug effects , Polyethylene Glycols/chemistry , Proto-Oncogene Proteins B-raf/genetics , Melanoma/immunology , Melanoma/drug therapy , Nanoparticles/chemistry , Cell Line, Tumor , Mice , Imiquimod/pharmacology , Adjuvants, Immunologic/administration & dosage , Adjuvants, Immunologic/pharmacology , Female , Polylactic Acid-Polyglycolic Acid Copolymer/chemistry , Macrophages/drug effects , Macrophages/immunology , Drug Liberation , Humans , Skin Neoplasms/immunology , Skin Neoplasms/prevention & control , Skin Neoplasms/drug therapyABSTRACT
Human skin is the largest organ and outermost surface of the human body, and due to the continuous exposure to various challenges, it is prone to develop injuries, customarily known as wounds. Although various tissue engineering strategies and bioactive wound matrices have been employed to speed up wound healing, scarring remains a significant challenge. The wound environment is harsh due to the presence of degradative enzymes and elevated pH levels, and the physiological processes involved in tissue regeneration operate on distinct time scales. Therefore, there is a need for effective drug delivery systems (DDSs) to address these issues. The objective of this review is to provide a comprehensive exposition of the mechanisms underlying the skin healing process, the factors and materials used in engineering DDSs, and the different DDSs used in wound care. Furthermore, this investigation will delve into the examination of emergent technologies and potential avenues for enhancing the efficacy of wound care devices.
Subject(s)
Skin , Wound Healing , Humans , Skin/pathology , Cicatrix/pathology , Tissue Engineering , Drug Delivery SystemsABSTRACT
Glioblastoma is an incurable cancer with a 5-year survival chance of less than 5%. Chemotherapy is a therapeutic approach to treating the disease; however, due to the presence of the blood-brain barrier (BBB), the probability of success is low. To overcome this issue, nanoparticles are promising carriers for crossing the BBB and delivering drugs to the tumor. In this study, the anticancer efficacy of doxorubicin (DOX) and carboplatin (CB) loaded into polyethylene glycol (PEG)ylated liposome nanoparticles (PEG-Lip) and in treating brain cancer was evaluated in vitro and in vivo. The results demonstrated that PEG-Lip-DOX/CB with a size of 212 ± 10 nm was synthesized that could release the loaded drugs in a controlled manner, from which 56.3% of the loaded drugs were released after 52 h. In addition, PEG-Lip-DOX/CB could significantly increase the cytotoxicity effects of the drugs against rat glioma C6 cells (IC50: 8.7 and 12.9 µM for the drugs-loaded nanoparticles and DOX + CB, respectively). The in vivo results also demonstrated that PEGylated liposomes, compared to non-PEGylated liposomes (Lip) and DOX + CB, were more efficient in increasing the therapeutic effects and decreasing the side effects of the drugs, in which the survival times of the glioblastoma-bearing rats were 39, 35, and 30 days in the PEG-Lip-DOX/CB, Lip-DOX/CB, and DOX + CB receiver groups, respectively. In addition, the weight loss was found to be 8.7, 10.5, and 13%, respectively, in the groups. The results of the toxicity evaluation were also confirmed by histopathological studies. Overall, the results of this study demonstrated that the encapsulation of DOX and CB into PEG-Lip is a promising approach to improving the properties of DOX and CB in terms of their therapeutic effects and drug side effects for the treatment of glioblastoma.
