Current drug delivery最新文献

Introduction/background: Methicillin-resistant Staphylococcus aureus (MRSA) pneumonia is one of the leading causes of death and an immense financial burden on healthcare systems. Rifaximin (RFX) has good antibacterial activity against MRSA, but its clinical application is limited due to its poor oral absorption.

Objective: In order to improve the oral bioavailability of rifaximin and expand the clinical application of RFX for MRSA pneumonia, this study developed a RFX-loaded myristic acid solid lipid nanoparticles (RFX-SLNs).

Methods: This study first screened the formula of RFX-SLNs through single factor screening. After that, the particle size, zeta potential and polydispersity index (PDI) of the RFX-SLNs were measured, the morphology of RFX-SLNs was observed by transmission electron microscopy, and the encapsulation efficiency (EE) and drug loading capacity (LC) of RFX-SLNs were detected by high performance liquid chromatography. Then, the sustained release ability and oral bioavailability of RFX-SLNs were studied through in vitro release and pharmacokinetics. Finally, the therapeutic effect of RFX-SLNs on MRSA pneumonia infection was studied by using a mouse MRSA pneumonia infection model.

Results: The optimal formulation of RFX-SLNs was 1% RFX with a water (3% PVA) and oil (myristic acid) ratio of 1:19. RFX-SLNs were spherical shape with a smooth surface and uniform size. The EE and LC of three different batches of RFX-SLNs were 89.35±2.47%, 90.45±3.69%, 88.72±1.18%, and 9.50 ± 0.01%, 10.09±0.01%, and 9.68±0.00%, respectively. In vitro release and pharmacokinetic studies showed that the myristic acid solid lipid nanoparticles showed excellent sustained release as expected and increased the oral bioavailability of RFX by 2.18 times. RFX-SLNs showed a good therapeutic effects in a mouse MRSA pneumonia infection model.

Conclusion: This study indicates that the myristic acid solid lipid nanoparticles might be an effective way to enhance the oral absorption and therapy effects of RFX and other insoluble drugs.

Ribavirin has been used as an antiviral agent to treat a variety of viral infections since the 1970s. Over the past few decades, studies have been conducted on the pharmacology of ribavirin, and the possibility of its use in new indications has been explored. According to the results of a number of studies, ribavirin efficacy in the therapy of malignant neoplasms of various genesis has been proven. Furthermore, due to the complexity of brain tumor therapy using surgical methods, targeted delivery of ribavirin to the brain becomes a promising alternative to existing treatment methods. Targeting of active pharmaceutical ingredient (API) to the brain tumor is achieved by intranasal drug delivery via a Nose-to-Brain mechanism. In addition, using this delivery mechanism, it is possible to reach the brain while bypassing the blood-brain barrier (BBB), thus avoiding the effects of the first passage through the liver. Despite the significant advantages of the method, there are limiting factors to its application - mucociliary clearance, which aims to remove foreign bodies from the surface of the nasal mucosa. In situ, systems are able to reduce the intensity of interfering factors on API and allow the achievement of maximum bioavailability during intranasal administration.

Different nanocarriers-based strategies are now extensively being used as an important strategy for improving drug efficacy and responsiveness, reducing toxicity issues related to drugs and harmful side effects, and overcoming the numerous significant difficulties related to absorption and bioavailability. Amongst different nanocarriers, nanovesicles are excellent and versatile systems for effectively delivering therapeutic agents, targeting ligand distribution and location. Nanovesicles are nanosized self-assembling spherical capsules with an aqueous core and one/- more lipid(s) layers. Several synthetic nanovesicles have been developed and investigated for their prospective uses in delivering drugs, proteins, peptides, nutrients, etc. Important procedures for nanovesicle manufacturing are thin-film hydration, unshaken method, ethanol injection, ether injection, proliposomes, freeze-drying, hot method, cold method, reverse-phase evaporation, and ultrasonication. Liposomes, liposomes, ethosomes, exosomes, and transferosomes (elastic vesicles) are the nonvesicular candidates extensively investigated to deliver antiviral drugs. This review article comprehensively overview different nanovesicles, their compositions, manufacturing, and applications as potential carriers for effectively delivering different antiviral drugs to treat viral diseases.

Chronic Obstructive Pulmonary Disease (COPD), a chronic lung disease that causes breathing difficulties and obstructs airflow from the lungs, has a significant global health burden and affects millions of people worldwide. The use of pharmaceuticals in COPD treatment is aimed to alleviate symptoms, improve lung function, prevent exacerbations, and enhance the overall quality of life for patients. Nanotechnology holds great promise to alleviate the burden of COPD. The main goal of this review is to present the full spectrum of therapeutics based on nanostructures for the treatment and management of COPD, including nanoparticles, polymeric nanoparticles, polymeric micelles, solid-lipid nanoparticles, liposomes, exosomes, nanoemulsions, nanosuspensions, and niosomes. Nanotechnology is just one of the many areas of research that may contribute to the development of more effective and personalized treatment modalities for COPD patients in the future. Future studies may be focused on enhancing the therapeutic effectiveness of nanocarriers by conducting extensive mechanistic investigations to translate current scientific knowledge for the effective management of COPD with little or no adverse effects.

Introduction: In the present study, a valnemulin hydrogen fumarate prodrug was characterized, its stability was compared with valnemulin hydrochloride, and the efficacy was evaluated in controlling pneumonia among mice experimentally infected with Actinobacillus pleuropneumoniae.

Methods: Optical microscopy, X-ray powder diffraction, infrared spectroscopy, and hydrogen nuclear magnetic resonance spectroscopy were used to study the physical and chemical properties of the prodrug. The thermal stability was investigated in comparison with valnemulin hydrochloride to improve the preparation process of valnemulin hydrogen fumarate soluble powder and maximize its drug effect. Additionally, the efficacy of valnemulin hydrogen fumarate was evaluated in a challenge-treatment trial in mice using an Actinobacillus pleuropneumoniae infection test in vivo.

Results: Valnemulin hydrogen fumarate had high crystallinity. After light irradiation for 20 days, valnemulin hydrogen fumarate did not degrade, whereas valnemulin hydrochloride did. These results showed that the valnemulin hydrogen fumarate was stable. At the same dose in drinking water, the valnemulin hydrogen fumarate was more effective than the reference drug of tiamulin fumarate in an Actinobacillus pleuropneumoniae challenge-treatment trial.

Conclusion: Valnemulin hydrogen fumarate shows excellent potential for application as a veterinary drug.

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.

Plant bioactives 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 naturallyderived 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 nano-formulations (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.

Background: Gemcitabine (Gem) is a well-known antineoplastic drug used to treat several solid tumors. The clinical application of Gem is hampered owing to its non-selectivity, short half-life, and drug resistance, which, therefore, necessitate the development of a suitable novel formulation that can selectively target cancer sites.

Methods: In present work, Gem-loaded bovine serum albumin nanoparticles (Gem-BSANPs) have been prepared by using the desolvation cross-linking method and coated with hyaluronic acid (HAGem- BSANPs) to target the CD44 receptor which overexpressed on several solid tumors. The developed NPs were characterized by particle size, zeta potential, Transmission Electron Microscopy (TEM), and Differential Scanning Calorimetry (DSC). Further anticancer activity of the developed formulation was evaluated against A549 and MCF-7 cells and explored mode of action studies.

Results: The mean particle size and zeta potential of HA-Gem-BSANPs were observed as 144.7±5.67 nm and -45.72±3.24 mV, respectively. The TEM analysis also corroborated the particle size and shape, while thermal analysis (DSC) indicated that Gem was entrapped into NPs in an amorphous form. The nucleoside transport inhibition assay demonstrated that the NPs do not depend on transporters for cellular internalization, and hence, resistance development in cells is less expected against this formulation. HA-Gem-BSANPs exhibited higher cytotoxicity and apoptosis on both the tested cell lines. However, better cell-killing ability and mitochondrial membrane potential loss were observed against A549 due to CD44 expression.

Conclusion: The present work demonstrated that HA-Gem-BSANPs could be a potential strategy to improve Gem's therapeutic efficacy by selectively targeting the tumor site.