Current drug delivery最新文献

The utilization of novel drug delivery systems loaded with essential oils has gained significant attention as a promising approach for biomedical applications in recent years. Plants possess essential oils that exhibit various medicinal properties, i.e., anti-oxidant, anti-microbial, anti- inflammatory, anti-cancer, immunomodulatory, etc., due to the presence of various phytoconstituents, including terpenes, phenols, aldehydes, ketones, alcohols, and esters. An understanding of conventional and advanced extraction techniques of essential oils (EOs) from several plant sources is further required before considering or loading EOs into drug delivery systems. Therefore, this article summarizes the various extraction techniques of EOs and their existing limitations. The in-built biological applications of EOs are of prerequisite importance for treating several diseases. Thus, the mechanisms of action of EOs for anti-inflammatory, anti-oxidant, anti-bacterial activities, etc., have been further explored in this article. The encapsulation of essential oils in micro or nanometric systems is an intriguing technique to render adequate stability to the thermosensitive compounds and shield them against environmental factors that might cause chemical degradation. Thus, the article further summarizes the advanced drug delivery approaches loaded with EOs and current challenges in the future outlook of EOs for biomedical applications.

Background: Adding a suitable surfactant can enhance the transdermal permeability of transethosomes while also leveraging its functionality as a functional material. In this study, transethosomes were prepared using D-α-tocopherol acid polyethylene glycol succinate (TPGS) as edge activators for transdermal delivery of curcumin (Cur).

Methods: The TPGS-mediated curcumin-loaded transethosomes (Cur@TES) were prepared and formulated optimally, and the optimized formulations were characterized for their morphology, particle size, entrapment efficiency (EE) and drug loading (DL). The stability and deformability of Cur@TES were investigated, while the transdermal delivery of Cur@TES was investigated through in vitro transdermal assays and fluorescence imaging. A mouse ear swelling model was performed to determine the anti-inflammatory effect of Cur@TES.

Results: Cur@TES appeared round or elliptical in shape. The particle size, EE and DL for the optimized formulation were observed as 131.2 ± 7.2 nm, 97.68 ± 2.26%, and 6.58 ± 0.62%, respectively. X-ray diffraction analysis confirmed the formation of disordered structures in the inner core of the vesicles. Moreover, Cur@TES system demonstrated better stability and deformability compared to the curcumin-loaded ethosomes (Cur@ES). In vitro transdermal experiments demonstrated that Cur@TES significantly increased the amount of drug retained in the skin (P<0.05). Fluorescence imaging confirmed that the skin distribution was distinctly enhanced with the delivery by TPGS mediated transethosomes. In addition, Cur@TES showed a significant inhibitory effect on Inflammatory swelling in the mouse ear-swelling model.

Conclusion: TPGS-mediated transethosomes exhibit significant transdermal advantages and enhanced anti-inflammatory effects, providing a new perspective for the transdermal delivery of curcumin.

Glioblastoma multiforme is the most common and aggressive malignant tumor that affects the central nervous system, with high mortality and low survival. Glioblastoma multiforme treatment includes resection tumor surgery, followed by radiotherapy and chemotherapy adjuvants. However, the drugs used in chemotherapy present some limitations, such as the difficulty of crossing the bloodbrain barrier and resisting the cellular mechanisms of drug efflux. The use of polymeric nanoparticles has proven to be an effective alternative to circumvent such limitations, as it allows the exploration of a range of polymeric structures that can be modified in order to control the biodistribution and cytotoxic effect of the drug delivery systems. Nanoparticles are nanometric in size and allow the incorporation of targeting ligands on their surface, favoring the transposition of the blood-brain barrier and the delivery of the drug to specific sites, increasing the selectivity and safety of chemotherapy. The present review has described the characteristics of chitosan, poly(vinyl alcohol), poly(lactic-coglycolic acid), poly(ethylene glycol), poly(β-amino ester), and poly(ε-caprolactone), which are some of the most commonly used polymers in the manufacture of nanoparticles for the treatment of glioblastoma multiforme. In addition, some of the main targeting ligands used in these nanosystems are presented, such as transferrin, chlorotoxin, albumin, epidermal growth factor, and epidermal growth factor receptor blockers, explored for the active targeting of antiglioblastoma agents.

In recent years, there has been an escalating interest in stimuli-responsive drug delivery systems (SRDDS) due to their ability to revolutionize the delivery of therapeutics. SRDDSs offer a multitude of benefits in comparison to conventional drug delivery systems (DDS), including spatiotemporal control of drug release, targeted delivery, and improved therapeutic efficacy. The development of various classes of stimuli-responsive DDS, such as pH-responsive, temperature-responsive, photo-responsive, redox responsive systems, has been propelled by advances in materials science, nanotechnology, and biotechnology. These systems exploit specific environmental or physiological cues to trigger drug release in a precisely controlled manner, making them highly promising for the treatment of various diseases. In this review article, an in-depth exploration of the principles, mechanisms, and applications of SRDDS in the context of diverse pathologies such as cancer, arthritis, Alzheimer's disease, atherosclerosis and tissue engineering has been provided. Furthermore, this article delves into the discussion of recent patents, market overview and the progress of research in clinical trials. Overall, this article underscores the transformative potential of SRDDS in enabling personalized, precise, and effective drug delivery for the treatment of the above-mentioned diseases.

Pharmaceutical grade sugars manufactured under Current Good Manufacturing Practice (cGMP) and complied with International Pharmaceutical Excipients Council (IPEC) quality standards, also contain a significant amount of nano-particulate impurities (NPIs). This review will focus on the origin of NPIs, the mechanism of their interference with Dynamic light scattering (DLS) and endotoxin tests, filtration technology to effectively reduce the NPIs, methodologies for analytical quantification of NPIs, guidance for setting the limits of threshold concentration and the overall impact of NPIs on the therapeutic activity, performance, stability of biopharmaceuticals and protein-based formulations. NPIs with an average particle size of 100 to 200 nm are present in sugars and are a combination of various chemicals such as dextrans (with the presence of β-glucans), ash, inorganic metal salts, aromatic colorants, etc. These NPIs primarily originate from raw materials and cannot be removed during the sugar refinement process. While it is commonly believed that filtering the final formulation with a 0.22 μ sterilizing grade filter removes all microbes and particles, it is important to note that NPIs cannot be filtered using this standard sterile filtration technology. Exceeding the threshold limit of NPIs can have detrimental effects on formulations containing proteins, monoclonal Antibodies (mAbs), nucleic acids, and other biopharmaceuticals. NPIs and β-glucans have a critical impact on the functionality and therapeutic activity of biomolecules and if present below the threshold limit of reaction, stability and shelf-life of biologics formulation will be greatly improved and the risk of immunogenic reactions must be significantly decreased.

A wide range of challenges are faced during the storage of blood products, including storage lesions, contamination that must be removed, and cell and protein damage due to chemicals and UV exposure. The enhancement of stability exhibited by gold nanoparticles (GNPs) is a notable advantage of these nanoparticles for the storage of blood products. The results of our review of articles from 2011 to 2022 discussing the effect of GNPs on blood products revealed that in RBCs, the dose, concentration, amount, and surface charge of GNPs significantly affect their compatibility. Purified GNPs were compatible with RBCs. Negatively charged GNPs with smaller diameters at lower concentrations were more compatible. However, in the plasma product, the nanoparticle surface modification with different agents showed greater compatibility. PEGylated nanospheres and GNPs exhibited higher albumin conformational stability than those coated with cetyltrimethylammonium bromide and rods. In the platelet product, smaller GNPs and high GNP concentrations induce platelet aggregation. PEGylation increased the platelet compatibility of GNP. The combination of GNPs with human fibrinogen and clopidogrel prevented clot formation. Finally, the findings of this investigation demonstrate that GNPs are contingent on their surface charge, dosage, and concentration.

Background: Alopecia is globally known as a distressing medical disorder that affects men and women, and current commercially available minoxidil solutions are formulated with irritant vehicles with frequent complaints of dermatologic adverse effects.

Objectives: This study aimed to investigate further the compatibility of ready-to-use vehicles for the preparation of tailored formulations for alopecia treatment, namely TrichoSol™ (a ready-to-use vehicle for personalized hair solutions) and TrichoFoam™ (a ready-to-use vehicle for personalized foam formulations), in combination with minoxidil and other active pharmaceutical ingredients (APIs), to establish adequate beyond-use dates (BUD) for the given formulations.

Methods: Products under evaluation were compounded using TrichoSol™ or TrichoFoam™, with direct incorporation of the APIs into these vehicles. Samples were then stored at controlled room temperature for up to 180 days. High-performance liquid chromatography (HPLC) methods were developed and validated, and then utilized to evaluate the compatibility of the APIs in TrichoSol™ and TrichoFoam™. Forced degradation studies were conducted to assess API stability under various stress conditions, and Antimicrobial Effectiveness Testing (AET) was performed at 0 and 180 days after compounding.

Results: According to our results, BUDs of up to 90-180 days were obtained for the examined formulations stored at room temperature, considering a degradation of maximum 10% of the nominal concentration of the APIs within them. The formulations exhibited no discernible physical alterations throughout this period and maintained chemical stability within acceptable limits. Microbiological evaluations confirmed the efficacy of the preservative system.

Conclusion: Products compounded with TrichoSol™ and TrichoFoam™ showed suitable stability to be used as personalized treatments for alopecia. We can then suggest that the vehicles TrichoSol™ and TrichoFoam™ present effective solutions for compounding personalized hair care treatments.

Introduction: DSPE-mPEG2000 is a phospholipid and polyethylene glycol conjugate used in various biomedical applications, including drug delivery, gene transfection, and vaccine delivery. Due to the hydrophilic and hydrophobic properties of DSPE-mPEG2000, it can serve as a drug carrier, encapsulating drugs in liposomes to enhance stability and efficacy.

Methods: In this study, long-circulating podophyllotoxin liposomes (Lc-PTOX-Lps) were prepared using DSPE-mPEG2000 as a modifying material and evaluated for their pharmacokinetics and anticancer activity.

Results: Lc-PTOX-Lps had an encapsulation rate of 87.11±1.77%, an average particle size of 168.91±7.07 nm, a polydispersity index (PDI) of 0.19±0.04, and a zeta potential of -24.37±0.36 mV. In vitro release studies showed that Lc-PTOX-Lps exhibited a significant slow-release effect. The long-circulating liposomes demonstrated better stability compared to normal liposomes and exhibited a significant slow-release profile. Pharmacokinetic studies indicated that Lc-PTOX-Lps had a prolonged half-life, reduced in vivo clearance, and improved bioavailability. Additionally, Lc-PTOX-Lps exhibited better anticancer effects on MCF-7 cells and lower toxicity to normal cells compared to PTOX.

Conclusion: Lc-PTOX-Lps were synthesized using a simple and effective method, and Lc-PTOXLps are promising anticancer agents.

Purpose: Reproducibility and scale-up production of microspheres through spray drying present significant challenges. In this study, biodegradable microspheres of Triamcinolone Acetonide Acetate (TAA) were prepared using a novel static mixing method by employing poly( lactic-co-glycolic acid) (PLGA) as the sustained-release carrier.

Methods: TAA-loaded microspheres (TAA-MSs) were prepared using a static mixing technique. The PLGA concentration, polyvinyl alcohol concentration (PVA), phase ratio of oil/water, and phase ratio of water/solidification were optimized in terms of the particle size, drug loading (DL), and encapsulation efficiency (EE) of TAA-MSs. The morphology of TAA-MSs was examined using Scanning Electron Microscopy (SEM), while the physicochemical properties were evaluated through X-ray diffraction (XRD), Differential Scanning Calorimetry (DSC), and Fourier Transform Infrared Spectroscopy (FT-IR). The in vitro release of TAA-MSs was compared to that of the pure drug (TAA) using a water-bath vibration method in the medium of pH 7.4 at 37°C.

Results: The formulation composition and preparation condition for the preparation of TAA-MSs were optimized as follows: the PLGA concentration was 1%, the phase ratio of oil(dichloromethane) /water (PVA solution) was 1:3, the phase ratio of water (PVA solution)/solidification was 1:2. The optimized TAA-MSs displayed spherical particles with a size range of 30-70 μm, and DL and EE values of 27.09% and 98.67%, respectively. Moreover, the drug-loaded microspheres exhibited a significant, sustained release, with 20% of the drug released over a period of 28 days. The XRD result indicated that the crystalline form of TAA in microspheres had been partly converted into the amorphous form. DSC and FT-IR results revealed that some interactions between TAA and PLGA occurred, indicating that the drug was effectively encapsulated into PLGA microspheres.

Conclusion: TAA-loaded PLGA microspheres have been successfully prepared via the static mixing technique with enhanced EE and sustained-release manner.

A feasible nano transdermal delivery system generally intends to have specific ideal and distinct characteristics primarily for safety, clinical efficacy, and boosted therapeutic index. The delivery of drugs, particularly macromolecules, across the skin is one of the most strenuous obstacles in front of pharmaceutical scientists. Technology advancement has provided some opportunities to overcome this difficulty by utilising microneedle arrays, ablation, laser methods etc. However, associated uneasiness, painful sensation, and higher cost of therapies limit their day-today use. Therefore, researchers have focused on developing alternate carriers like ultra-deformable liposomes, also termed transfersomes. Transfersomes are composed of a lipid bilayer containing phospholipids and an edge activator to facilitate drug delivery via transdermal route to deeper layers of skin and for higher systemic bioavailability. The bilayer structure of transfersomes allows ease of encapsulation of both hydrophilic and lipophilic drugs with higher permeability than typical liposomes. Therefore, among various vesicular systems, transfersomes have developed much interest in targeted and sustained drug delivery. The current review primarily emphasizes critical aspects of transfersomes, including their applications, clinical trial studies, and patents found in various literature sources.