Current drug delivery最新文献

Plant bioactive are being used since the early days of medicinal discovery for their various therapeutic activities and are safer compared to modern medicines. According to World Health Organization (WHO), approximately 180,000 deaths from burns occur every year with the majority in countries. Recent years have witnessed significant advancements in this domain, with numerous plant bioactive and their various nanoformulations demonstrating promising preclinical burn wound healing activity and identified plant-based nanotechnology of various materials through some variations of cellular mechanisms. A comprehensive search was conducted on scientific databases like PubMed, Web of Science, ScienceDirect and Google Scholar to retrieve relevant literature on burn wound, plants, nano formulations and in vivo studies from 1990 to 2024. From a total of approximately 180 studies, 40 studies were screened out following the inclusion and exclusion criteria, which reported 40 different plants and plant extracts with their various nano-formulations (NFs) that were used against burn wounds preclinically. This study provides the current scenario of naturally-derived targeted therapy, exploring the impact of natural products on various nanotechnology in burn wound healing on a preclinical model. This comprehensive review provides the application of herbal nanoformulations (HBNF) for the treatment of burn wounds. Natural products and their derivatives may include many unidentified bioactive chemicals or untested nano-formulations that might be useful in today's medical toolbox. Mostly, nano-delivery system modulates the bioactive compound's effectiveness on burn wounds and increases compatibility by suppressing inflammation. However, their exploration remains incomplete, necessitating possible pathways and mechanisms of action using clinical models.

Diabetic Foot Ulcer (DFU) is a chronic wound, and a person with diabetes has an increased lifetime risk of foot ulcers (19%-34%) and high morbidity (65% recurrence in 3-5 years, 20% lifetime amputation). Recent data have shown rising amputation rates, especially in the younger and minority populations. This abstract discusses innovative approaches for addressing this issue. This highlights the use of nanotechnology-based drug nanocomposite systems for natural wound healing therapies, with a focus on nanoparticles, nano-emulsions, and nanogels. This review also emphasizes the potential of hydrogels for drug delivery, highlighting their versatility in various medical applications. Furthermore, it delves into the use of silver nanoparticles (AgNP's) for treating diabetic wounds while acknowledging the need to address potential toxicity concerns. Finally, the abstract discusses the utilization of traditional herbal medicine and the integration of modern science to advance wound care, particularly focusing on wound microbiome, immune response, and controlled herbal medicine delivery. This study also highlights clinical trials conducted on DFU. Overall, these abstracts highlight the importance of exploring diverse and innovative solutions to chronic wound management.

Nanostructured lipid carriers (NLCs) are lipidic nanocarriers that recover the permanency and capacity of drug payloads. NLCs are well-known as second-generation lipid nanocarriers with an unstructured matrix, presenting potentially advantageous nanocarrier systems with marketable opportunities because of reproducible production methodologies and biocompatible lipidic excipients. These (NLCs) are now recognized as a very promising nanocarrier structure for the efficient delivery of drugs via different administration routes. In recent years, several NLC-based gels have been developed and evaluated for topical delivery of many drugs and other therapeutic agents. This review article presents an overview of NLC-based topical gels investigated to deliver drugs via ocular, dermal, and transdermal routes. In addition, the classification, manufacturing, characterizations, advantages, and disadvantages of NLCs are addressed in this article. We also discussed different evaluations of NLC-based topical gels.

Background: Fungal keratitis (mycotic keratitis) is an eye infection in which the cornea is infected by fungi and such fungal keratitis management can be effectively possible by ocular administration of antifungal drugs.

Objective: The main objectives of the present research were to develop and evaluate fluconazoleloaded transfersomal hydrogels for ocular delivery in the effective management of fungal keratitis.

Methods: A 23 factorial design-based approach was used for statistical optimization, where (A) the ratio of lipid to edge activators, (B) the amount of hyaluronic acid (% HA), and (C) the ratio of edge activators (sodium deoxycholate to Span 80) were taken as three factors. The average vesicle diameter (Z, nm) of transfersomes was taken as a response. Further, fluconazole-loaded transfersomes (FTO) were incorporated into 1% Carbopol 940-based hydrogel (OF1) and 2% HMPC K4M-based hydrogel (OF2) containing D-panthenol (5% w/w).

Results: The optimal variable setting for the optimized formulations of FTO was (A) = 9.15, (B) = 0.30%, and (C) = 3.00. FTO exhibited 66.39 nm Z, 0.247 polydispersity index, - 33.10 mV zeta potential, and 65.38 ± 1.77 % DEE, and desirable elasticity. TEM image of FTO demonstrated a unilamellar vesicular structure. The ex vivo ocular permeation of fluconazole from transfersomal hydrogels was sustained over 24 h. All the transfersomal hydrogels showed good bioadhesion and excellent antifungal activity with respect to the zone of inhibition against Candida albicans than Aspergillus fumigates, in vitro. HET-CAM study results demonstrated that both the hydrogels were nonirritant and safe for ocular. Short-term physical stability study suggested the stability of the developed formulation.

Conclusion: The current research demonstrated a new way to enhance the ocular penetration of fluconazole via transfersomal hydrogel formulations for ocular delivery in the effective management of fungal keratitis.

Background: Breast cancer remains a significant global health challenge, with thymoquinone showing promise as a therapeutic agent, but hindered by poor solubility.

Objective: This study aimed to enhance TQ delivery to MCF-7 breast cancer cells using mesitylene- mesoporous silica nanoparticles coated with liposomes, designed for controlled drug release.

Methods: Nanoparticles were synthesized using the sol-gel method and coated with phosphatidylserine- cholesterol liposomes. Different nanocharacterization techniques and in vitro assays were employed to assess the drug release kinetics, cellular uptake, cytotoxicity, and apoptosis.

Results: The nanoparticles exhibited favorable properties, including a large pore size of 3.6 nm, a surface area of 248.96 m2/g, and a hydrodynamic size of 171.571 ± 8.342 nm with a polydispersity index of 0.182 ± 0.017, indicating uniformity and stability. The successful lipid bilayer coating was confirmed by a zeta potential shift from +6.25 mV to -5.65 mV. The coated nanoparticles demonstrated a slow and sustained drug release profile, with cellular uptake of FITC-formulated nanoparticles being approximately 5-fold higher than free FITC (P < 0.0001). Cytotoxicity assays revealed a significant reduction in cell viability (P < 0.0001), reaching an IC50 value of 25 μM at 48 hours. Apoptosis rates were significantly higher in cells treated with the formulated TQ compared to the free drug and control at both 24 and 48 hours (P < 0.0001).

Conclusion: This nanoformulation significantly enhanced TQ delivery, offering a promising strategy for targeted breast cancer therapy. Further preclinical studies are recommended to advance this approach in cancer treatment.

Background: Metastatic melanoma poses a significant threat globally, with a distressingly low ten-year survival rate of only 10%. While FDA-approved treatments such as dacarbazine and high-dose IL-2 have been employed in clinical settings, their limitations underscore the urgent need for more effective therapies.

Aims: This study aimed to develop a potential anticancer local treatment through the extraction of various amounts of ginger extract loaded unto Poly(vinyl alcohol) (PVA) nanofibers.

Methods: The anticancer activity of the produced membranes was studied on human skin melanoma B16F10 cells. Other in vitro experiments such as cell migration assay, cell proliferation assay, cell viability assay, scanning electron microscopy assay, real-time PCR assay, and ant-inflammatory assay were performed for the in vitro characterization of the delivery system. Tissue toxicity of the developed patches was studied in a rat model.

Results: The study showed that scaffolds loaded with 2%, 4%, 6%, 8%, and 0% of ginger extract had around 784.98 ± 202.31 nm, 771.86 ± 219.07 nm, 820.65 ± 242.43 nm, 785.19 ± 203.99 nm, and 671.29 ± 184.09 nm of mean fiber size, respectively. The ginger extract-loaded membranes suppressed the growth and migration activity of human skin melanoma B16F10 cells in a dose and time-dependent manner. Real-time PCR assay showed that the developed membranes modulated the expression levels of Ras/ERK and PI3K/AKT signaling pathways. Animal study results showed that our developed patches were not toxic against liver or skin tissues.

Conclusion: Ginger extract-loaded PVA nanofibers exhibited promising anticancer potential against melanoma cells, suggesting a viable localized treatment option.

Introduction/objective: The spread of tumors (48% in men and 51% in women), as well as the protection of malignant tumors by stromal cells and complex blood vessels, pose significant challenges to drug delivery to tumors. Modern chemotherapy, on the other hand, addresses tumor growth suppression by at least 60% through versatile formulation systems and numerous modifications to drug delivery systems. The renewable and naturally occurring polymers present invariably in all living cells form the fundamental foundation for most anticancer drug development. The review aims to discuss in detail the preparations of polysaccharide, lipid, and protein-based drug-loading vehicles for the targeted delivery of prominent anticancer drugs. It also provides an explanation of drug distribution in blood (cumulative releases of nearly 80% drug) and drug accumulation at tumor sites (1-5 mg/kg) due to enhanced permeability and retention (EPR).

Methods: Specific delivery examples for treating colorectal and breast carcinomas have been presented to distinguish the varied drug administration, bioavailability, and tumor internalization mechanisms between sugar, fatty acid, and amino acid polymers. Current therapy possibilities based on cutting-edge literature are provided, along with drug delivery systems tailored to tumor location and invasive properties.

Results: The unique combinations of the three natural polymers provide unparalleled solutions to minimize the toxicity (<20% drug release) of the chemotherapeutic drugs on normal tissues. Moreover, the development of a consolidated drug delivery system has contributed to a substantial reduction (dose reduction from 10.43 μM to 1.9 μM) in the undesirable consequences of higher dosages of chemotherapeutic drugs.

Conclusion: The review extensively covers safe chemotherapeutic systems with significant advantages (tumor volume shrinkage of 4T1 cells from 1000 mm3 to 200 mm3) in clinical applications of carcinoma treatments using natural polymers.

Background: Our previous studies have found that Wumei Pills can regulate the intestinal flora to inhibit chemotherapy-induced intestinal mucositis (CIM). However, there is still insufficient evidence to confirm that intestinal flora is the main link in the regulation of CIM by Wumei Pills, and its downstream mechanism is still unclear.

Method: We first obtained the signal pathway of the intervention of Wumei Pill on CIM through network pharmacological analysis and then transplanted the bacterial solution into CIM mice, combined with Western Blot, HE, ELISA and other biological technology-related proteins and inflammatory factors.

Results: It showed that 97 kinds of effective ingredients and 205 kinds of targets of Wumei pills were screened out and the potential mechanism of Wumei Pills on CIM may be the NF-κB signaling pathway. In contrast with the control group, the results displayed that the weight, food intake, and mice's colon length were apparently decreased in the 5-Fu group, while the diarrhea score was increased. However, FMT reversed this change, and the difference was statistically significant. Additionally, FMT could improve the pathological state of inflammatory cell infiltration in mice, reduce histopathological scores of colon and jejunum, decrease the expression levels of IL-1β, MPO, TNF-α, and IL-6, reverse the activation of signaling pathway named TLR4/Myd88/ NF-κB and down-regulate protein expression, thereby exerting its anti-inflammatory activities. Further experiments have found that FMT could reverse the decreasing of tight junction proteins and mucins caused by 5-Fu, thereby repairing the intestinal mucosal barrier, and FMT could also increase the content of acetic acid, propanoic acid, and butanoic acid in the feces of 5-Fu group.

Conclusion: FMT can defend the intestinal mucosal barrier integrality by increasing the content of exercise fatty acids, and its mechanism may be in connection with its inhibition of TLR4/My- D88/NF-κB signal pathway to relieve inflammation.

The development of nanotechnology-based drug delivery systems has been extensively investigated across various therapies, leading to the creation of numerous nanomedicines for clinical use. However, these nanomedicines have yet to achieve the anticipated therapeutic efficacy in clinical settings, highlighting the urgent need for further research in this area. A primary challenge in nanomedicine research lies in ensuring that nanoparticles and therapeutic agents can effectively penetrate and accumulate within tumors. The enhanced permeability and retention (EPR) effect has been previously explored as a means to enhance drug delivery to tumors, but recent findings have revealed its limitations, including variable responses, restricted penetration, clearance by the reticuloendothelial system, and non-specific accumulation. As an alternative approach, transcytosis has been explored for delivering drugs to specific organs or tissues, potentially bypassing some of the constraints of the EPR effect. For example, nanoparticles can be guided through barriers by targeting specific receptors on cell surfaces or by utilizing a different charge compared to tumor cells' surfaces. Therefore, this article explores transcytosis, including adsorptive, receptor-mediated, and cell-mediated subtypes, all of which have demonstrated promising results and offer potential solutions to enhance the effectiveness of nanomedicine delivery for cancer therapy.

Introduction: The last strategy in targeted drug delivery systems is to deliver the anticancer drug to the tumor tissue to increase its therapeutic effect and minimize its undesirable side effects. In line with this goal in this research, the redox/pH-responsive disulfide magnetic nanocarriers based on PF127-NH2/L-cysteine-CM-β-CD-FA were synthesized and evaluated in a doxorubicin delivery system.

Methods: We effectively surrounded Fe3O4 nanoparticles with SiO2 using the sol-gel method, and then confidently coated them with oleic acid on Fe3O4@SiO2 nanoparticles.. In another reaction, a PF127-NH2/L-cysteine-CM-β-CD-FA was synthesized. The process involved modifying pluronic F127 (PF 127) with maleic anhydride and aminating it to form PF127-NH2. The obtained PF127-NH2 was attached to L-cysteine, followed by condensing with carboxymethyl-β-cyclodextrin and then functionalized by folic acid. Finally, PF127-NH2/L-cysteine-CM-β-CD-FA was coated on the surface of magnetic nanoparticles, and the resulting PF127-NH2/L-cysteine-CM-β-CD-FA was disulfidated to form the final nanocarrier network, which was abbreviated as LCMNPs-SS. The doxorubicin was used as a model drug and loaded into the LCMNPs-SS nanocarrier.

Results: The LCMNPs-SS nanocarrier exhibited excellent properties for controlled release, with a well-defined release rate, a controllable level by an external magnet, and adjusting by DLdithiothreitol concentration. The LCMNPs-SS nanocarrier could also break apart when exposed to an oxidant or a change in pH. This meant that the drug release could be fine-tuned in response to temperature, pH, or more than one stimulus.

Conclusion: These drug-carrying systems are valuable in reducing the dose of doxorubicin. High internalization of the synthesized LCMNPs-SS caused sped cellular uptake.