Current drug delivery最新文献

Introduction: Assessing the cytotoxicity of gold nanoparticles (GNPs) has gained importance due to their development in the biomedical field.

Method: In this study, we systematically synthesized gold nanorods (GNRs), gold nanobipyramids (GNBPs), and gold nanocups (GNCs) using a seed-mediated method, with an average length of 32.53 ± 4.67 nm, 72.90 ± 7.54 nm and 118.01 ± 11.02 nm, respectively.

Results: Furthermore, using the cell counting kit-8 (CCK-8) assay, we assessed the cellular cytotoxicity of three different types of GNPs with various different surface coatings, such as organic cetyltrimethylammonium bromide (CTAB) and polyethylene glycol (PEG). The results showed that the cytotoxic behavior of GNPs was shape-dependent in the concentration range of 3.125 -100 μg/mL. The types of GNPs and their surface coating had a significant impact on how the GNPs behaved in cells. Compared to PEG-coated GNPs, which do not induce cell injury, CTAB-coated GNPs show more noticeable cytotoxicity.

Conclusion: Furthermore, compared to GNCs, the toxicity of GNRs and GNBPs against GES-1 cells, RAW 264.7 cells and LX-2 cells was greater. Our research provides an important new understanding of the effects of surface modification on the biocompatibility and the shape of GNPs in the biomedical field.

Background: Eczema, an inflammatory skin disease causing intense itching, is a function of a range of internal and external factors, impacting individuals of all ages and leading to economic loss. Inflammation is the most important manifestation of eczema, and Matricaria recutita essential oil (MREO) extracted from Matricaria recutita possesses excellent antibacterial and anti-inflammatory properties.

Methods: In this study, Matricaria recutita microemulsions were prepared by the trans-phase emulsification method and their stability was determined by evaluating the relevant indexes. Establishment of 2,4-dinitro-chlorobenzene-induced AD model in mice. Detection of serum indexes of IL-6, IL-17, and TNF-α, and on pathological tissue sections, the HE staining, toluidine blue staining, immunohistochemistry, and observation were performed.

Results: The study obtained optimal conditions for the preparation of microemulsion formulations of Matricaria recutita. Through quality evaluation, it was found that the microemulsion increased stability, reduced irritation, and retained anti-inflammatory activity and therapeutic effects on eczema compared to Matricaria recutita essential oil (MREO). Studies have demonstrated that microemulsion formulations of Matricaria recutita and Matricaria recutita significantly down regulate the proinflammatory factors TNF-α, IL-17, and IL-6. It was shown by hematoxylin-eosin (HE) staining that both Matricaria recutita essential oil (MREO) and Matricaria recutita microemulsion (MRME) improved the inflammatory status of eczematous skin tissues in mice. The number of mast cells expressed in the tissues was decreased in the surface-treated group, as shown by toluidine blue staining. Additionally, the number of mast cells expressed in the tissues in the surface-treated group was reduced, as demonstrated by immunohistochemistry. Furthermore, immunohistochemistry revealed that MREO and MRME have immunomodulatory effects on the tissues.

Conclusion: The study showed that microemulsion formulations of Matricaria recutita may serve as a novel remedy for eczema.

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.

Background: Hot-melt Pressure-sensitive Adhesives (HMPSA) are eco-friendly pressuresensitive adhesives, with the potential of being used as substrates for transdermal patches. However, due to the low hydrophilicity of HMPSA, the application is limited in the field of Traditional Chinese Medicine (TCM) plasters.

Methods: Three modified HMPSA were prepared with acrylic resin EPO, acrylic resin RL100, and Polyvinylpyrrolidone (PVP) as the modifying materials. The physical compatibility between HMPSA and the modifying materials was investigated through in vitro release performance, viscosity, softening point, cohesion, and fluidity, so as to determine the most effective modifying material. The impact of the modified HMPSA on the release properties of different TCM ingredients was elucidated by the performance of water absorption and contact angle behavior.

Results: With the addition of the modifying materials, both the viscosity and the softening point of HMPSA were improved, with the flowability reduced and the cohesion maintained. The morphological and structural changes reflected the physical compatibility between HMPSA and the three modifying materials. According to the results of in vitro release experiments, PVP effectively improved the release performance of paeoniflorin, ephedrine hydrochloride, and cinnamaldehyde in HMPSA, with no significant impact on the release performance of eugenol. The changes in the drug release performance of HMPSA may be attributed to the improved hydrophilicity of HMPSA after physical modification.

Conclusion: The compatibility and the drug release performance of HMPSA were effectively enhanced after the addition of the modifying materials by the physical blending technique. Among the three modifying materials, PVP has been found to be an ideal modifying material for HMPSA in the field of TCM plasters due to its effects on drug release performance.

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.

Pharmaceutical giants (e.g., Ashland, Bausch & Lomb, Johnson & Johnson, Medtronic, Neurelis, etc.) promote the growth of hydrogels globally. Hydrogel-based drug delivery system (DDS) market size accounted for USD 6415 million in 2021 and is estimated to reach USD 12,357 million by 2030, with a compound annual growth rate (CAGR) of 7.6% from 2022 to 2030. Hydrogels, characterized by their unique three-dimensional networks of hydrophilic polymers, have emerged as a keystone in the advancement of biomaterial science. Existing trends in the advancement of hydrogel drug delivery systems (DDS) involve the release of drugs in response to specific triggers such as pH, temperature, or enzymes for targeted drug delivery and to reduce the potential for systemic toxicity. They excel in their ability to achieve high drug loading capacities, their ease of manufacturing, and their inherent biocompatibility and biodegradability. These attributes not only promise crucial mechanistic features but also offer robust protection for labile drugs and enable the encapsulation of multiple therapeutic agents. Thus, hydrogels stand as promising candidates in various biomedical and pharmaceutical applications, ensuring controlled release and compatibility essential for therapeutic efficacy. Additionally, hydrogels have massive applications in tissue engineering, wound healing, cosmetics, and biomaterials (e.g., contact lenses and implantable devices). Furthermore, hydrogels possess the capability to release active drug(s) under sustained conditions as recommended. Their exceptional qualities position hydrogels as a preferred choice on a global scale. Moreover, they enhance bioavailability, optimize dosage regimens, promote patient compliance, and minimize adverse effects. Furthermore, hydrogels are recommended for use in clinical trials to enhance therapeutic drug delivery outcomes. Despite their remarkable properties, hydrogels do have certain disadvantages, including expensive manufacturing costs and incompatibility with certain drugs. The author has highlighted the fundamental ideas about hydrogels, their classification, global scenario, current developments in the field, and their potential applications. Overall, hydrogel application is progressing rapidly, toward more proficient and effective DDS in the future.

Introduction: A serious public health condition called liver fibrosis can cause cirrhosis, cancer, and even patient death.

Method: This study sought to determine if Luteolin (LUT) and Silibinin (SBN) could protect rats against oxidative stress and liver fibrosis caused by thioacetamide (TAA) over three weeks, as well as any potential mechanisms of action. There will be 49 adult Wistar albino rats utilized, split up into 7 groups: (G1) Negative control, (G2) Positive control, (G3) LUT+TAA, (G4) SBN+TAA, (G5) mix LUT+ SBN, (G6) LUT+SBN with TAA, (G7) LUT+SBN then TAA, and so. Liver function tests and oxidative stress markers were measured after the experiment. The liver underwent microscopic inspection. Rats given TAA treatment had significantly higher liver enzymes than control; yet, albumin (ALB), total protein (TP), superoxide dismutase (SOD), and reduced glutathione (GSH) significantly decreased.

Results: Following three weeks of TAA exposure, liver sections revealed hepatocytic damage and fibrosis. Oxidative stress, histological alterations, and alterations in liver function were all lessened in TAA rats administered with LUT, SBN, or both.

Conclusion: The combined hepatoprotective benefits of LUT and SBN prevented TAA-induced biochemical and histological alterations in rat liver, acting in concert with each other.

Small nucleic acids (sNA) are revolutionizing several therapeutic environments in areas such as oncology as well as rare disease states. However, despite the progress in RNA modification, lipid nanoparticles (LNPs), and GalNAc conjugation methods, issues like toxicity, immunogenicity, and stability limitations affect the application. Compared with viral and non-viral systems, LNPs have become more credible carriers to solve the problems of RNA degradation and realize more innovation, such as the first RNA interference drug, Patisiran. Likewise, methods for GalNAc conjugation have enabled liver-targeting therapies with better pharmacokinetic profiles. Relative to this subject, novel strategies such as exosome-mediated delivery and multifaceted systems involving LNP-GalNAc and exosome all hold more specificity and biostability. Some of the recent advancements in RNA chemical modifications involve the application of 1-methylpseudouridine which enhances the stability of the RNA and also reduces its immunogenic outcomes. Also, the application of AI in therapeutic areas includes establishing the delivery vectors, estimating severe side effects, and designing new nucleic acid therapies. In addition to hepatic targeting, tissue targetability is now being investigated for other purposes. A solution to the existing stability and targeting limitations is critical for the further development and enhanced use of sNA therapies in broad diseases, including chronic and complex diseases. The major focus of this review is on the recent development and potential future trends of sNA as a drug delivery system for precision medicine.

Background: Combining Doxorubicin (DOX) with sorafenib (SF) is a promising strategy for treating Hepatocellular Carcinoma (HCC). However, strict dosage control is required for both drugs, and there is a lack of target selectivity.

Objective: This study aims to develop a novel nano-drug delivery system for the combined use of DOX and SF, aiming to reduce their respective dosages, enhance therapeutic efficacy, and improve target selectivity.

Methods: DOX/SF co-loaded liposomes (LPs) were prepared using the thin-film hydration method. The liposomes were modified with 1,2-distearoyl-sn-glycero-3-phospho-ethanolamine (DSPE)- polyethylene glycol (PEG2000), DSPE-PEG1000-cell penetrating peptide TAT, and Glycyrrhetinic Acid (GA). The basic properties of the liposomes were characterized. CCK-8 cell viability assays were conducted using HepG2, MHCC97-H, and PLC cell models, and apoptosis experiments were performed using HepG2 cells to determine if this delivery system could reduce the respective dosages of DOX and SF and enhance HCC cytotoxicity. Liposome uptake experiments were performed using HepG2 cells to validate the target selectivity of this delivery system.

Results: A GA/TAT-DOX/SF-LP liposomal nano drug delivery system was successfully constructed, with a particle size of 150 nm, a zeta potential of -7.9 mV, a DOX encapsulation efficiency of 92%, and an SF encapsulation efficiency of 88.7%. Cellular experiments demonstrated that this delivery system reduced the required dosages of DOX and SF, exhibited stronger cytotoxicity against liver cancer cells, and showed better target selectivity.

Conclusion: A simple and referenceable liposomal nano drug delivery system has been developed for the combined application of DOX and SF in hepatocellular carcinoma treatment.

Conjugated Linoleic Acid (CLA) is a polyunsaturated dietary fatty acid. Probiotics can biohydrogenate CLA with multiple health benefits, especially in cancer treatment. In vitro, in vivo, and clinical studies have confirmed CLA isomers to possess anti-cancer activity. CLA has demonstrated its potential as an alternative treatment for cancer and also used as an adjuvant to reduce the side effects of existing treatment methods. The mechanism of the anticancer activity of CLA is still not clear; however, it may involve intervention with the cell cycle and modulation of gene expression. A greater potential of CLA for cancer treatment has been supported by more and more clinical trials to evaluate its potential. Some advanced technologies are in progress to overcome the flaws of current methods and enhance the microbial production of CLA. In conclusion, nutritional enrichment as a functional food and direct consumption of CLA may contribute to cancer management.