Current drug delivery最新文献

With the advent of ivermectin, tremendous improvement in public health has been observed, especially in the treatment of onchocerciasis and lymphatic filariasis that created chaos mostly in rural, sub-Saharan Africa and Latin American countries. The discovery of ivermectin became a boon to millions of people that had suffered in the pandemic and still holds its pharmacological potential. Ivermectin continued to surprise scientists because of its notable role in the treatment of various other tropical diseases (Chagas, leishmaniasis, worm infections, etc.) and is viewed as the safest drug with the least toxic effects. The current review highlights its role in unexplored avenues towards forging ahead of the repositioning of this multitargeted drug in cancer, viral (the evaluation of the efficacy of ivermectin against SARS-Cov-2 is under investigation) and bacterial infection and malaria. This article also provides a glimpse of regulatory considerations of drug repurposing and current formulation strategies. Due to its broad-spectrum activity, multitargeted nature and promising efforts are put towards the repurposing of this drug throughout the field of medicine. This single drug originated from a microbe, changed the face of global health by proving its unmatched success and progressive efforts continue in maintaining its bequestnin the management of global health by decreasing the burden of various diseases worldwide.

Background: Chemoresistance continues to limit the recovery of patients with cancer. New strategies, such as combination therapy or nanotechnology, can be further improved.

Objective: In this study, we applied the computational strategy by exploiting two databases (CellMiner and Prism) to sort out the cell lines sensitive to both anti-cancer drugs, paclitaxel (PTX) and dihydroartemisinin (DHA); both of which are potentially synergistic in several cell lines.

Methods: The combination of PTX and DHA was screened at different ratios to select the optimal ratio that could inhibit lung adenocarcinoma NCI-H23 the most. To further enhance therapeutic efficacy, these combinations of drugs were incorporated into a nanosystem.

Results: At a PTX:DHA ratio of 1:2 (w/w), the combined drugs obtained the best combination index (0.84), indicating a synergistic effect. The drug-loaded nanoparticles sized at 135 nm with the drug loading capacity of 15.5 ± 1.34 and 13.8 ± 0.56 corresponding to DHA and PTX, respectively, were used. The nano-sized particles improved drug internalization into the cells, resulting in the significant inhibition of cell growth at all tested concentrations (p < 0.001). Additionally, α-tubulin aggregation, DNA damage suggested the molecular mechanism behind cell death upon PTX-DHA-loaded nanoparticle treatment. Moreover, the rate of apoptosis increased from approximately 5% to more than 20%, and the expression of apoptotic proteins changed 4 and 3 folds corresponding to p-53 and Bcl-2, respectively.

Conclusion: This study was designed thoroughly by screening cell lines for the optimization of formulations. This novel approach could pave the way for the selection of combined drugs for precise cancer treatment.

Background: Nanotechnology is rapidly advancing in almost every area, such as the pharmaceutical industry, food industry, nano fabrics, electronics, wastewater treatment, and agriculture.

Introduction: Metallic nanoparticles are commonly used in various fields but are especially important in the pharmaceutical industry. Metallic nanoparticles have a size range of 10 nm to 100 nm.

Methods: Two techniques are used to synthesize metallic nanoparticles, the top-down approach and the bottom-up approach. These techniques can be synthesized using three different methods: physical, chemical, and biological. Chemical methods include coprecipitation, reduction, sonochemical, solvothermal, and others, while physical methods include discharge, milling, and ion implantation. Biological methods include plants and their extracts, agricultural wastes, microorganisms, and seaweeds. Scanning electron microscopy, transmission electron microscopy, dynamic light scanning, and other techniques are used to characterize them.

Results: All metallic nanoparticles are biocompatible and have special optical, electrical, magnetic, and chemical properties. They are used in various industries, including the pharmaceutical industry as an anticancer agent, antibacterial, antifungal, antioxidant, antidiabetic, and biosensors. Gold, silver, iron oxide, zinc oxide, platinum, copper oxide, and palladium nanoparticles are the most common metal nanoparticles used in the pharmaceutical industry. Monometallic and multimetallic nanoparticles are broadly classified under this.

Conclusion: This article focuses on the major metallic nanoparticle groups, including synthesis, applications, case studies, toxicity, regulatory aspects and innovative approaches to metallic nanomaterials.

Objective: In order to overcome the insolution and low bioavailability of the vitexin in vivo, β-cyclodextrin-vitexin (β-CD-vitexin) microspheres were prepared, and their effects on the proliferation of SW480 cells were observed.

Methods: Scanning electron microscopy, ultraviolet spectrum, Fourier transform infrared spectroscopy, and release rate analysis identified the formation of β-CD-vitexin microspheres. MTT assay detected the effect of β-CD-vitexin microspheres on tumor cell proliferation at 6, 12, 24, and 48 h. Fluorescence microscopy and flow cytometry were used to observe the effect of β-CD-vitexin microspheres on the apoptosis of SW480 cells. The mRNA expression of the p53 gene was measured by qPCR.

Results: β-CD-vitexin microspheres were successfully prepared. SW480 cell proliferation was inhibited by 0.1, 0.2, and 0.4 mg/mL of β-CD-vitexin microspheres in a dose- and time-dependent manner, and the mechanism of proliferation inhibition was related to cell apoptosis caused by the upregulated expression of p53 gene.

Conclusion: The preparation of β-CD-vitexin sustained release microspheres is feasible, and β-CDvitexin microspheres have potential anti-colorectal cancer value.

Background: The antiretroviral protease inhibitor drug, lopinavir (LPV), is used to treat HIV-1 infection. LPV is known to have limited oral bioavailability, which may be attributed to its poor aqueous solubility, low efficacy and high first-pass metabolism. Self-nanoemulsifying drug delivery systems (SNEDDS) for LPV have been developed and optimised to counter the current issues.

Methods: The titration method was used to prepare LPV-loaded SNEDDS (LPV-SNEDDS). Six different pseudo-ternary phase diagrams were constructed to identify the nanoemulsifying region. The developed formulations were chosen in terms of globule size < 100 nm, dispersity ≤ 0.5, dispersibility (Grade A) and% transmittance > 85. Heating-cooling cycle, freeze-thaw cycle, and centrifugation studies were performed to confirm the stability of the developed SNEDDS.

Results: The final LPV-SNEDDS (L-14) droplet size was 58.18 ± 0.62 nm, with polydispersity index, zeta potential, and entrapment efficiency (EE%) values of 0.326 ± 0.005, -22.08 ± 1.2 mV, and 98.93 ± 1.18%, respectively. According to high-resolution transmission electron microscopy (HRTEM) analysis, the droplets in the optimised formulation were < 60 nm in size. The selected SNEDDS released nearly 99% of the LPV within 30 min, which was significantly (p < 0.05) higher than the LPV-suspension in methylcellulose (0.5% w/v). It indicates the potential use of SNEDDS to enhance the solubility of LPV, which eventually could help improve the oral bioavailability of LPV. The Caco-2 cellular uptake study showed a significantly (p < 0.05) higher LPV uptake from the SNEEDS (LPV-SNEDDS-L-14) than the free LPV (LPV-suspension).

Conclusion: The LPV-SNEDDS could be a potential carrier for LPV oral delivery.

Nanosponges are colloidal and crosslinked nanocarriers consisting of a solid mesh-like network with nanocavities to encompass various types of substances like antineoplastic, proteins, peptides, volatile oil, DNA and then incorporated into topical medications that are mainly formulated such as gels, creams, lotions, ointments, liquid and powders etc. for topical drug delivery system. In the polymeric construction of nanosponges, the release of enthalpy-rich water molecules accounts for high complexation efficiency for different molecular substances. The benefits of nanosponges involve the extended and controlled release of encapsulated particles with excellent competence and great stability. Nanosponges assume a significant part in new varieties of medicaments, beautifiers, farming, horticulture, high atomic weight containing proteins, innovative fire retardants, gas transporters, and water filters. Nanosponges are a novel technology that offers controlled and targeted drug delivery by various routes like oral, parenteral, and topical routes. Nanosponges are an effective transporter for biologically active ingredients; therefore, it is broadly employed in anti-cancer, antiviral, antiplatelet, and antilipidemic therapy. This review article gives attention to the general introduction, merits and demerits, classification, characteristic features, procedures for developing nanosponges, and numerous factors which affect nanosponge formulation, evaluation parameters, and applications in the medicinal industry.

Traditional Chinese medicine (TCM) has a good curative effect, but its disadvantages include complex components, poor drug stability, potential drug interaction, etc. Therefore, it is particularly important to construct a novel drug delivery system that can load Chinese medicine monomers to solve this problem. Silk fibroin is a kind of natural polymer material with unique properties. It can be used as a carrier material to load Chinese medicine monomers to prepare novel drug delivery systems that significantly affect treating diseases without toxic and side effects. However, there is still a lack of a review on silk fibroin as a carrier material to load Chinese medicine monomers to explore and analyze the current research results and progress. Here, our article focuses on the in-depth excavation and analysis of the recent research on novel drug delivery systems prepared by silk fibroin and TCM monomers. Besides, the characteristics, existing problems, and prospects of silk fibroin are discussed and explained. It is hoped that this research can provide a reference and basis for the modernization of TCM, the design of novel drug delivery systems, the research and development of new drugs in the future, and contribute to the innovation of silk protein.

The vagina is an essential part of the female reproductive system and offers many potential benefits over conventional drug delivery, including a large surface area for drug absorption, relatively low enzymatic activity, avoiding first-pass effects, and ease of administration. The vaginal mucosal cavity is an effective route for administering therapeutic agents that are intended both for local and systemic administration. The present review provides a comprehensive overview of recent trends and developments in vaginal drug delivery. Marketed formulations and products under clinical study are also reviewed. Various novel vaginal delivery systems have been studied in recent years as effective tools for delivering a range of therapeutic agents to the vagina. These systems offer numerous benefits, including sustained delivery, improved bioavailability, effective permeation, and higher efficacy. The recent focus of the scientific community is on the development of safe and efficient drug delivery systems, such as nanoparticles, microparticles, vesicular systems, vaginal rings, microneedles, etc., for vaginal application. Various factors, such as the physicochemical properties of the drugs, the volume and composition of the vaginal fluid, the pH of the vaginal fluid, the thickness of the vaginal epithelium, and the influence of sexual intercourse may influence the release of drugs from the delivery system and subsequent absorption from the vaginal route. To date, only a limited number of in vivo studies on novel vaginal DDS have been reported. Additionally, drug release kinetics under varying vaginal environments is also not well understood. More research is needed to ensure the suitability, biocompatibility, and therapeutic effectiveness of novel DDS for vaginal delivery. Although numerous strategies and interventions have been developed, clinical translation of these systems remains a challenge. The toxicity of the carrier system is also an important consideration for future clinical applications.

Oral administration of drug is the most preferred one among the other routes for the majority of clinical applications. As compared to the parenteral method of administration, it has potential benefits such as increased patient compliance, fewer problems, and reduced treatment costs. Regardless of these factors, inadequate bioavailability owing to poor solubility or permeability limits the therapeutic effectiveness of orally given drugs. Though most current research focuses on BCS II (drugs with low solubility and high permeability), BCS III (drugs with high solubility and low permeability) also has poor oral bioavailability due to their limited permeability across lipid membranes and is usually administered through the parenteral route. The need for an oral alternative to parenteral administration has prompted a renewed focus on the development of innovative dosage forms that support the absorption of medicines that are poorly permeable through the intestinal epithelium. Because of their unique sizedependent feature in enhancing transmembrane permeability, ability to incorporate both lipophilic and hydrophilic drugs and biocompatible nature of components, the use of nanoparticles for improving drug bioavailability has been a focus of current study in the field of drug delivery in recent years. The lipidbased nanoparticle method presents a potential new avenue for manufacturing BCS Class III medicines with enhanced bioavailability, as poor permeability is the main issue for these agents. This research aims to assess the potential of lipid nanoparticles for improving the oral bioavailability of medicines with permeability-restricted oral absorption, such as pharmaceuticals in Biopharmaceutical Classification System (BCS) class III.

Since the discovery of insulin, continuous developments of this peptide have led to better management of diabetes mellitus, thus leading to a decrease in diabetes-related mortality. Despite these developments, we have seen an increase in diabetes cases, which has further necessitated more innovative methods for diabetes management. The subcutaneous administration of insulin remains the mainstay therapy for type 1 diabetes mellitus. However, despite the availability of insulin analogues with improved pharmacokinetics, challenges with conventional administration exist. The challenges associated with insulin injections include hypoglycaemic episodes, needle phobia, and injection-site inflammation, which all have been reported to reduce patient compliance. Ongoing research on diabetes management strives to develop therapies that provide improved glycaemic control with minimal side effects. In part, for these reasons, we have seen an increase in the search and development of alternative insulin delivery systems that are envisaged to circumvent the shortfalls associated with the conventional administration route. Several alternative drug delivery systems, such as oral, pulmonary, buccal, nasal, and transdermal, have been explored in the last century. These efforts have not been without victory, as we have seen the emergence of pulmonary (Exubera and Afrezza) and buccal insulin delivery systems licenced for therapeutic use. Despite the success seen in these two systems, their marketability and popularity have been severely compromised due to reported safety concerns. Although oral insulin delivery has always shown promise in the past decades; however, it was only limited to preclinical trials. The main challenge associated with this delivery route is poor bioavailability, which necessitates high insulin concentration to be administered. Due to recent developments, oral insulin has reached phase 3 clinical trials. It is believed that patients would prefer oral insulin as their preference is often observed for oral antidiabetics over injected ones. In the last decade, transdermal insulin has also gained interest, where delivery of insulin with a concomitant reduction in blood glucose concentration has been demonstrated in vivo. However, at present, there are no clinical studies that have reported the efficacy of transdermal insulin administration. With technological advancement, there is a potential to develop yet another insulin delivery system that would likely enter the markets. As these novel delivery systems have been found to be effective, emerging competing products should be welcome and appreciated.