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.

Age-related macular degeneration (ARMD) is a degenerative ocular disease that is the most important cause of irreversible vision loss in old-aged people in developed countries. Around fifty percent of vision impairments in developed countries are due to ARMD. It is a multifaceted disease that is associated with both genetic and environmental risk factors. The most important treatments option for ARMD includes laser photocoagulation, photodynamic therapy (PDT), Anti-VEGF Injections, and combination therapies. In this review, we also propose that topical ocular drug delivery with nanocarriers has more attention for the treatment of ARMD. The nanocarriers were specially designed for enhanced corneal residential time, prolonged drug release and action, and minimizing the frequency of administrations. Different types of nanocarriers were developed for the topical ocular delivery system, such as nanomicelles, nanoemulsions, nanosuspensions, liposomes, and polymeric nanoparticles. These topical ocular nanocarriers were administered topically, and they can fix the hydrophobic substances, increase solubility and improve the bioavailability of an administered drug. Hence the topical ocular delivery systems with nanocarriers provide a safe and effective therapeutic strategy and promising tool for the treatment of posterior segment ocular diseases ARMD.

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.

Clay materials are widely used in drug delivery systems due to their unique characteristics. Montmorillonite is a major component of bentonite and it has a large surface area, better swelling capacity, and high adsorption capacity. The modification of natural bentonite could improve its sorption ability for new emerging applications. Recent advancements in the polymer-silicate composite have novel biomedical applications in drug delivery, tissue regeneration, wound healing, cancer therapy, enzyme immobilization, diagnostic and therapeutic devices, etc. Perspective view of the montmorillonite- polymer composite as a pharmaceutical carrier in drug delivery systems has been discussed in this review. Different types of modification of montmorillonite for the development of pharmaceutical formulations have also been documented. Many challenges in clay nanocomposite systems of polymer of natural/synthetic origin are yet to be explored in improving antimicrobial properties, mechanical strength, stimuli responsiveness, resistance to hydrolysis, etc. Drug interaction and binding capability, swelling of clay may be carried out for finding possible applications in monitoring delivery systems. Pharmaceutical properties of active drugs in the formulation could also be improved along with dissolution rate, solubility, and adsorption. The clay-incorporated polymeric drug delivery systems may be examined for a possible increase in swelling capacity and residence time after mucosal administration.

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.

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.

Introduction: In this study, an in situ gel-forming chitosan hydrogel was prepared with the use of glutamate salt of chitosan (Ch-Ga), β-glycerophosphate (Gp), and morphine (Mor). The paper is focused on in vitro physicochemical properties and in-vivo analgesic effects of the prepared chitosan hydrogel.

Method: The thermosensitive properties of prepared chitosan hydrogel were evaluated during the different temperatures and times. The physicochemical properties of chitosan hydrogel were investigated by infrared (IR) spectroscopy and X-ray diffraction analysis (XRD). Also, its cell cytotoxicity effects were evaluated in murine NIH/3T3 normal cells. Subsequently, the distribution of chitosan hydrogel in the nasal cavity of rats and its analgesic responses were evaluated. The prepared chitosan hydrogel showed that it could be gelled at the temperature of 34 °C before leaving the nose in the shortest possible time of 30 s.

Result: The analgesic responses of the intranasal (IN) injection of chitosan hydrogel (IN-chitosan hydrogel, 10 mg Mor/kg) in a single unit dose in rat relative to the placebo and intranasal or intraperitoneal (IP) injection of free morphine solution (IN-Free Mor or IP-Free Mor, 10 mg Mor/kg) via the hot plate test, reveal that the IN-chitosan hydrogel could induce fast analgesic effects of morphine with maximum possible effect (MPE) of 93% after 5 min compare to the IN-Free Mor and IP-Free Mor with MPE of 80% after 15 min and 66% after 30 min, respectively. Also, prolonged analgesic effects with MPE of 78 % after 6 h of injection were only seen in the IN-chitosan hydrogel injected group. The obtained fluorescent images of rat's brain injected with IN-chitosan hydrogel containing doxorubicine (Dox) as a fluorescent agent showed that the mucosal adhesive and absorption enhancer properties of IN-chitosan hydrogel resulting in longer presence of them in the nasal cavity of rats followed by more absorption of Dox from the blood vessels of olfactory bulbs with a 74% color intensity compared to the IN-Free Mor and IN-Free Dox with 15%.

Conclusion: These data reveal that the IN-chitosan hydrogel could induce fast and prolonged analgesic effects of morphine compare to the IN/IP-Free Mor, which could be considered as an in situ gel-forming thermosensitive chitosan hydrogel for nasal delivery of wide ranges of therapeutic agents.

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.

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.