Current drug delivery最新文献

Background: Due to the lifestyle of people in the community in recent years, the prevalence of diabetes mellitus has increased, so New drugs and related treatments are also being developed.

Introduction: One of the essential treatments for diabetes today is injectable insulin forms, which have their problems and limitations, such as invasive and less admission of patients and high cost of production. According to the mentioned issues, Theoretically, Oral insulin forms can solve many problems of injectable forms.

Methods: Many efforts have been made to design and introduce Oral delivery systems of insulin, such as lipid-based, synthetic polymer-based, and polysaccharide-based nano/microparticle formulations. The present study reviewed these novel formulations and strategies in the past five years and checked their properties and results.

Results: According to peer-reviewed research, insulin-transporting particles may preserve insulin in the acidic and enzymatic medium and decrease peptide degradation; in fact, they could deliver appropriate insulin levels to the intestinal environment and then to blood. Some of the studied systems increase the permeability of insulin to the absorption membrane in cellular models. In most investigations, in vivo results revealed a lower ability of formulations to reduce BGL than subcutaneous form, despite promising results in in vitro and stability testing.

Conclusion: Although taking insulin orally currently seems unfeasible, future systems may be able to overcome mentioned obstacles, making oral insulin delivery feasible and producing acceptable bioavailability and treatment effects in comparison to injection forms.

γ-Polyglutamic acid is a kind of biomaterial and environmentally friendly polymer material with the characteristics of water solubility and good biocompatibility. It has a wide range of applications in medicine, food, cosmetics and other fields. This article reviews the preparation, characterization and medical applications of γ-polyglutamic acid nanoparticles. Nanoparticles prepared by using γ- polyglutamic acid not only had the traditional advantages of enhancing drug stability and slow-release effect, but also were simple to prepare without any biological toxicity. The current methods of nanoparticle preparation mainly include the ion gel method and solvent exchange method, which use the total electrostatic force, van der Waals force, hydrophobic interaction force and hydrogen bond force between molecules to embed materials with different characteristics. At present, there are more and more studies on the use of γ-polyglutamic acid to encapsulate drugs, and the research on the mechanism of its encapsulation and sustained release has gradually matured. The development and application of polyglutamic acid nanoparticles have broad prospects.

The plateau is a typical extreme environment with low temperature, low oxygen and high ultraviolet rays. The integrity of the intestinal barrier is the basis for the functioning of the intestine, which plays an important role in absorbing nutrients, maintaining the balance of intestinal flora, and blocking the invasion of toxins. Currently, there is increasing evidence that high altitude environment can enhance intestinal permeability and disrupt intestinal barrier integrity. This article mainly focuses on the regulation of the expression of HIF and tight junction proteins in the high altitude environment, which promotes the release of pro-inflammatory factors, especially the imbalance of intestinal flora caused by the high altitude environment. The mechanism of intestinal barrier damage and the drugs to protect the intestinal barrier are reviewed. Studying the mechanism of intestinal barrier damage in high altitude environment is not only conducive to understanding the mechanism of high altitude environment affecting intestinal barrier function, but also provides a more scientific medicine treatment method for intestinal damage caused by the special high altitude environment.

When breast cells divide and multiply out of control, it is called breast cancer. Symptoms include lump formation in the breast, a change in the texture or color of the breast, or a discharge from the nipple. Local or systemic therapy is frequently used to treat breast cancer. Surgical and radiation procedures limited to the affected area are examples of local management. There has been significant worldwide progress in the development of monoclonal antibodies (mAbs) since 1986, when the first therapeutic mAb, Orthoclone OKT3, became commercially available. mAbs can resist the expansion of cancer cells by inducing the destruction of cellular membranes, blocking immune system inhibitors, and preventing the formation of new blood vessels. mAbs can also target growth factor receptors. Understanding the molecular pathways involved in tumor growth and its microenvironment is crucial for developing effective targeted cancer therapeutics. Due to their unique properties, mAbs have a wide range of clinical applications. Antibody-drug conjugates (ADCs) are drugs that improve the therapeutic index by combining an antigen-specific antibody with a payload. This review focuses on the therapeutic applications, mechanistic insights, characteristics, safety aspects, and adverse events of mAbs like trastuzumab, bevacizumab, pertuzumab, ertumaxomab, and atezolizumab in breast cancer treatment. The creation of novel technologies utilizing modified antibodies, such as fragments, conjugates, and multi-specific antibodies, must be a central focus of future studies. This review will help scientists working on developing mAbs to treat cancers more effectively.

Until the drugs enter humans life, they may face problems in transportation, drug delivery, and metabolism. These problems can cause reducing drug's therapeutic effect and even increase its side effects. Together, these cases can reduce the patient's compliance with the treatment and complicate the treatment process. Much work has been done to solve or at least reduce these problems. For example, using different forms of a single drug molecule (like Citalopram and Escitalopram); slight changes in the drug's molecule like Meperidine and α-Prodine, and using carriers (like Tigerase®). PEGylation is a recently presented method that can use for many targets. Poly Ethylene Glycol or PEG is a polymer that can attach to drugs by using different methods and resulting sustained release, controlled metabolism, targeted delivery, and other cases. Although they will not necessarily lead to an increase in the effect of the drug, they will lead to the improvement of the treatment process in certain ways. In this article, the team of authors has tried to collect and carefully review the best cases based on the PEGylation of drugs that can help the readers of this article.

Introduction: With the rapid development of nanotechnology, the research and development of nano-drugs have become one of the development directions of drug innovation. The encapsulation of the nanoparticles can change the biological distribution of the drug in vivo and improve the bioavailability of the drug in vivo. Naringenin is poorly soluble in water and has a low bioavailability, thus limiting its clinical application. The main purpose of this study was to develop a nano-sized preparation that could improve the oral bioavailability of naringenin.

Methods: Chitosan oligosaccharide modified naringenin-loaded bovine serum albumin nanoparticles (BSA-COS@Nar NPs) were prepared by emulsification solvent evaporation and electrostatic interaction. The nanoparticles were characterized by HPLC, laser particle size analyzer, transmission electron microscope and X-ray diffraction analysis. The release in vitro was investigated, and the behavior of nanoparticles in rats was also studied. The caco-2 cell model was established in vitro to investigate the cytotoxicity and cellular uptake of nanoparticles.

Results: BSA-COS@Nar NPs were successfully prepared, and the first-order release model was confirmed in vitro release. In vivo pharmacokinetic results indicated that the area under the drug concentration- time curve (AUC) of BSA-COS@Nar NPs was 2.37 times more than free naringenin. Cytotoxicity and cellular uptake results showed that BSA-COS@Nar NPs had no significant cytotoxic effect on Caco- 2 cells and promoted cellular uptake of the drug.

Conclusion: BSA-COS@Nar NPs could improve the in vivo bioavailability of naringenin.

Background: Bacterial infection can delay wound healing and is therefore a major threat to public health. Although various strategies have been developed to treat bacterial infections, antibiotics remain the best option to combat infections. The inclusion of growth factors in the treatment approach can also accelerate wound healing. The co-delivery of antibiotics and growth factors for the combined treatment of wounds needs further investigation.

Objective: Here we aimed to develop antibiotic and growth factor co-loaded nanoparticles (NPs) to treat Staphylococcus aureus-infected wounds.

Methods: By using our previously prepared reactive oxygen species-responsive material (Oxi-αCD), roxithromycin (ROX)-loaded NPs (ROX/Oxi-αCD NPs) and recombinant human epidermal growth factor (rhEGF)/ROX co-loaded NPs (rhEGF/ROX/Oxi-αCD NPs) were successfully fabricated. The in vivo efficacy of this prepared nanomedicine was evaluated in mice with S. aureus-infected wounds.

Results: ROX/Oxi-αCD NPs and rhEGF/ROX/Oxi-αCD NPs had a spherical structure and their particle sizes were 164 ± 5 nm and 190 ± 8 nm, respectively. The in vitro antibacterial experiments showed that ROX/Oxi-αCD NPs had a lower minimum inhibitory concentration than ROX. The in vivo animal experiments demonstrated that rhEGF/ROX/Oxi-αCD NPs could significantly accelerate the healing of S. aureus-infected wounds as compared to the free ROX drug and ROX/Oxi-αCD NPs (P < 0.05).

Conclusion: ROX and rhEGF co-loaded NPs can effectively eliminate bacteria in wounds and accelerate wound healing. Our present work could provide a new strategy to combat bacteria-infected wounds.

Background: Rheumatoid arthritis (RA) is a systemic autoimmune disease (AD), and the global incidence rate is 0.5 ~ 1%. Existing medications might reduce symptoms, however, there is no known cure for this illness. Etanercept (EN) can competitively inhibit TNF-α binding to the TNF receptor on the cell surface to treat RA. However, subcutaneous injection of free EN predisposes to systemic distribution and induces immune system hypofunction. Draining lymph nodes (LNs) play a significant role in the onset, maintenance, and progression of RA as they are the primary sites of aberrant immune response and inflammatory cytokine production.

Aim: The purpose of this study was to successfully treat RA with etanercept by encapsulating it in nanoemulsions (NEs/EN) and then delivering it specifically to draining LNs. The EN-loaded NEs were prepared by high-pressure homogenization method and modified with DSPE-mPEG₂₀₀₀ and Ca(OH)₂.

Methods: A novel nano-emulsion (NE) was constructed to deliver EN (NE/EN) to RA-draining LNs. To decrease aggregation and load EN, DSPE-mPEG₂₀₀₀ and Ca(OH)₂ were successively decorated on the surface of the lipid injectable emulsions. The hydrodynamic diameter and morphology of NEs/EN were investigated by using a laser particle size analyzer and transmission electron microscopy, respectively. The in vivo fluorescence imaging system was used to study the in vivo LN targeting ability of the formulation. In the therapeutic experiment, NEs/EN was subcutaneously administrated to inhibit the development of the mouse arthritis model.

Results: Circular dichroism spectrum and L929 cell experiment confirmed that NEs encapsulation had no impact on the biological activity of EN. In vivo investigation on collagen-induced arthritis (CIA) mouse model showed that NEs/EN have good inguinal lymph node targeting capabilities, as well as, anti-inflammatory effect against RA. Compared with the free group, the paw thickness and arthritic score in NEs/EN group were significantly alleviated. Moreover, the concentration of pro-inflammatory cytokines TNF-α and IL-1β in NEs/EN-treated mice was lower than that in free EN.

Conclusion: NEs/EN effectively improve the effectiveness of EN in the treatment of RA. Our work provides an experimental foundation for expanding the clinical application of EN.

Background: Among various materials designed for anticancer drug transport, sulfide nanoparticles are uniquely intriguing owing to their spectral characteristics. Exploration of newer nanoscale copper sulfide particles with dysprosium doping is reported herein. It leads to a change in the physicochemical properties of the sulfide nanoparticles and hence the difference in drug release and cytotoxicity.

Objective: We intend to purport the suitably engineered cobalt sulfide and dysprosium-doped cobalt sulfide nanoparticles that are magnetic and NIR-absorbing, as drug delivery vehicles. The drug loading and release are based on the supramolecular drug complex formation on the surface of the nanoparticles.

Method: The nanomaterials are synthesized employing hydrothermal procedures, coated with a biocompatible poly-β-cyclodextrin, and characterized using the methods of diffractometry, microscopy, spectroscopy, thermogravimetry and magnetometry. The sustained drug release is investigated in vitro. 5-Fluorouracil is loaded in the nanocarriers. The empty and 5-fluorouracil-loaded nanocarriers are screened for their anti-breast cancer activity in vitro on MCF-7 cells.

Results: The size of the nanoparticles is below 10 nm. They show soft ferromagnetic characteristics. Further, they show broad NIR absorption bands extending up to 1200 nm, with the dysprosium-doped material displaying greater absorbance. The drug 5-fluorouracil is encapsulated in the nanocarriers and released sustainably, with the expulsion duration extending over 10 days. The IC₅₀ of the blank and the drug-loaded cobalt sulfide are 16.24 ± 3.6 and 12.2 ± 2.6 μg mL^-1, respectively. For the drug-loaded, dysprosium-doped nanocarrier, the IC₅₀ value is 9.7 ± 0.3 μg mL^-1.

Conclusion: The ultrasmall nanoparticles possess a size suitable for drug delivery and are dispersed well in the aqueous medium. The release of the loaded 5-fluorouracil is slow and sustained. The anticancer activity of the drug-loaded nanocarrier shows an increase in efficacy, and the cytotoxicity is appreciable due to the controlled release. The nanocarriers show multi-functional characteristics, i.e., magnetic and NIR-absorbing, and are promising drug delivery agents.

Despite the technological advancement in the era of personalized medicine and therapeutics development, infectious parasitic causative agents remain one of the most challenging areas of research and development. The disadvantages of conventional parasitic prevention and control are the emergence of multiple drug resistance as well as the non-specific targeting of intracellular parasites, which results in high dose concentration needs and subsequently intolerable cytotoxicity. Nanotechnology has attracted extensive interest to reduce medication therapy adverse effects including poor bioavailability and drug selectivity. Numerous nanomaterials-based delivery systems have previously been shown in animal models to be effective in the treatment of various parasitic infections. This review discusses a variety of nanomaterials-based antiparasitic procedures and techniques as well as the processes that allow them to be targeted to different parasitic infections. This review focuses on the key prerequisites for creating novel nanotechnology-based carriers as a potential option in parasite management, specifically in the context of human-related pathogenic parasitic agents.