Use Of Drug Delivery Systems Research Articles

Progress in Antimelanoma Research of Natural Triterpenoids and Their Derivatives: Mechanisms of Action, Bioavailability Enhancement and Structure Modifications

Melanoma is one of the most dangerous forms of skin cancer, characterized by early metastasis and rapid development. In search for effective treatment options, much attention is given to triterpenoids of plant origin, which are considered promising drug candidates due to their well described anticancer properties and relatively low toxicity. This paper comprehensively summarizes the antimelanoma potential of natural triterpenoids, that are also used as scaffolds for the development of more effective derivatives. These include betulin, betulinic acid, ursolic acid, maslinic acid, oleanolic acid, celastrol and lupeol. Some lesser-known triterpenoids that deserve attention in this context are 22β-hydroxytingenone, cucurbitacins, geoditin A and ganoderic acids. Recently described mechanisms of action are presented, together with the results of preclinical in vitro and in vivo studies, as well as the use of drug delivery systems and pharmaceutical technologies to improve the bioavailability of triterpenoids. This paper also reviews the most promising structural modifications, based on structure–activity observations. In conclusion, triterpenoids of plant origin and some of their semi-synthetic derivatives exert significant cytotoxic, antiproliferative and chemopreventive effects that can be beneficial for melanoma treatment. Recent data indicate that their poor solubility in water, and thus low bioavailability, can be overcome by complexing with cyclodextrins, or the use of nanoparticles and ethosomes, thus making these compounds promising antimelanoma drug candidates for further development.

Theranostic siRNA loaded mesoporous silica nanoplatforms: A game changer in gene therapy for cancer treatment

Growing interest has been seen in non-pathogenic, safe, and effective gene therapy delivery systems. There are many nucleic acid therapies that have been studied to alter the expression of DNA or RNA, such as mRNA, siRNA, antisense DNA, and microRNA (miRNA), of which siRNA has been shown to be useful in blocking specific genes. The development of an efficient nucleic acid delivery method is crucial for molecular diagnostic and therapeutic systems. Mesoporous silica nanoparticles (MSNs) with high porosity, good textural qualities, and biocompatibility have been studied for use in drug delivery systems. They are being utilized more and more in combination therapy, gene silencing, and other biological applications, especially in cancer nanomedicine. MSNs offer efficient drug loading and controlled release, and additions can change their characteristics. They are widely employed in target medication delivery, biosensing, cellular uptake, and diagnostics in the biomedical field. Additionally, they have been connected to theranostic drugs for cancer treatment. This review highlights the current state of knowledge of MSNs and their specialized applications as theranostic agents for cancer management.

Activity of antioxidant enzymes in hepatocytes of mice with lymphoma under the action of thiazole derivative in complex with polymeric nanocarrier

Many chemotherapeutics drugs have low water solubility, which potentially can decrease their anticancer potential. The use of drug delivery systems has proven to be highly effective in addressing the challenges associated with delivering hydrophobic chemotherapy drugs to tumor tissues. However, two major issues that arise in the clinical nanoparticle-based treatment of cancer are hepatotoxicity and suppression of the hematopoietic system, which can limit their medical applicability. As previously established, thiazole derivative N-(5-benzyl-1,3-thiazol-2-yl)-3,5-dimethyl-1-benzofuran-2-carboxamide in complex with polymeric nanocarriers (nanomicelles) based on polyethylene glycol exhibited a greater level of cytotoxicity towards specific tumor cell lines melanoma, glioblastoma, hepatocarcinoma, leukemia, etc. This compound and its complexes with polymeric nanomicelle significantly changed the activity of antioxidant enzymes in lymphoma cells. Therefore, the purpose of this study was to examine the impact of a thiazole derivative with polymeric nanomicelles based on polyethylene glycol on the hepatocytes (liver cells) of mice that had been implanted with Nemet-Kelner lymphoma. The investigated compounds thiazole derivative, polymeric nanomicelle, and combination of thiazole derivative with nanomicelle at a final concentration of 10 μM were added to the liver samples and incubated for 10 min. The activity of antioxidant defense system enzymes such as superoxiddismutase, catalase, glutathionperoxidase was determined in liver homogenate under the action of studied compounds in vitro. It was reported that neither thiazole derivative, nanomicelle, nor their complex changed the activity of antioxidant enzymes in hepatocytes from mice with lymphoma. Thiazole derivative and it complex with nanomicelle had limited negative side effects in the mice with lymphoma. The investigated compounds were not hepatotoxic toward murine liver cells.

Preparation of Cubosomes with Improved Colloidal and Structural Stability Using a Gemini Surfactant.

Cubosomes are nanoparticles with bicontinuous cubic internal nanostructures that have been considered for use in drug delivery systems (DDS). However, their low structural stability is a crucial concern for medical applications. Herein, we investigated the use of a gemini surfactant, sodium dilauramidoglutamide lysine (DLGL), which is composed of two monomeric surfactants linked with a spacer to improve the structural stability of cubosomes prepared with phytantriol (PHY). Uniform nanosuspensions comprising a specific mixing ratio of DLGL and PHY in water prepared via ultrasonication were confirmed by using dynamic light scattering. Small-angle X-ray scattering and cryo-transmission electron microscopy revealed the formation of Pn3̅m cubosomes in a range of DLGL/PHY solid ratios between 1 and 3% w/w. By contrast, cubosome formation was not observed at DLGL/PHY solid ratios of 5% w/w or higher, suggesting that excess DLGL interfered with cubosome formation and caused them to transform into small unilamellar vesicles. The addition of phosphate-buffered saline to the nanosuspension caused aggregation when the solid ratio of DLGL/PHY was less than 5% w/w. However, Im3̅m cubosomes were obtained at solid ratios of DLGL/PHY of 6, 7.5, and 10% w/w. The lattice parameters of the Pn3̅m and Im3̅m cubosomes were approximately 7 and 11-13 nm, respectively. The lattice parameters of Im3̅m cubosomes were affected by the concentration of DLGL. Pn3̅m cubosomes were surprisingly stable for 4 weeks at both 25 and 5 °C. In conclusion, DLGL, a gemini surfactant, was found to act as a new stabilizer for PHY cubosomes at specific concentrations. Cubosomes composed of DLGL are stable under low-temperature storage conditions, such as in refrigerators, making them a viable option for heat-sensitive DDS.

Review of Recent Advances in the Use of Drug Delivery Systems in Ophthalmology

Review of Recent Advances in the Use of Drug Delivery Systems in Ophthalmology

Collagen-Based Hydrogels for the Eye: A Comprehensive Review.

Collagen-based hydrogels have emerged as a highly promising platform for diverse applications in ophthalmology, spanning from drug delivery systems to biomedical interventions. This review explores the diverse sources of collagen, which give rise to different types of collagen protein. The critical isolation and purification steps are discussed, emphasizing their pivotal role in preparing collagen for biomedical use. To ensure collagen quality and purity, and the suitability of collagen for targeted applications, a comprehensive characterization and quality control are essential, encompassing assessments of its physical, chemical, and biological properties. Also, various cross-linking collagen methods have been examined for providing insight into this crucial process. This comprehensive review delves into every facet of collagen and explores the wide-ranging applications of collagen-based hydrogels, with a particular emphasis on their use in drug delivery systems and their potential in diverse biomedical interventions. By consolidating current knowledge and advancements in the field, this review aims to provide a detailed overview of the utilization of engineered collagen-based hydrogels in ocular therapeutics.

Innovative Strategies for Drug Delivery to the Ocular Posterior Segment.

Innovative and new drug delivery systems (DDSs) have recently been developed to vehicle treatments and drugs to the ocular posterior segment and the retina. New formulations and technological developments, such as nanotechnology, novel matrices, and non-traditional treatment strategies, open new perspectives in this field. The aim of this mini-review is to highlight promising strategies reported in the current literature based on innovative routes to overcome the anatomical and physiological barriers of the vitreoretinal structures. The paper also describes the challenges in finding appropriate and pertinent treatments that provide safety and efficacy and the problems related to patient compliance, acceptability, effectiveness, and sustained drug delivery. The clinical application of these experimental approaches can help pave the way for standardizing the use of DDSs in developing enhanced treatment strategies and personalized therapeutic options for ocular pathologies.

Metal-organic frameworks for efficient drug adsorption and delivery

In recent years, the number of materials used as drug delivery systems (DDS) has increased dramatically. The widespread use of DDSs has improved both the safety and efficacy of therapy. The systems currently in use pose numerous drawbacks and require proper improvements. Although many modern materials are being developed, metal-organic frameworks (MOFs) deserve special attention. Thermal and chemical stability, high specific surface area, low toxicity, high biocompatibility, and great potential for modification are the main features enabling MOFs to be used as DDS. In this review, we describe MOFs, their structure, synthesis, and characterization, as well as drug loading, drug release kinetics, and bioassays. A critical approach is to outline the disadvantages as well as the limitations of MOFs and to identify areas that need to be studied more thoroughly. Nonetheless, the prospective nature of MOFs as DDS and potential adsorbents in overdose or poisoning is presented and highlighted.

Preparation of imidazole acids grafted chitosan with enhanced antioxidant, antibacterial and antitumor activities

Herein, imidazole acids grafted chitosan derivatives were synthesized, including HACC, HACC derivatives, TMC, TMC derivatives, amidated chitosan and amidated chitosan bearing imidazolium salts. The prepared chitosan derivatives were characterized by FT-IR and 1H NMR. The tests evaluated the biological antioxidant, antibacterial, and cytotoxic activities of chitosan derivatives. The antioxidant capacity (DPPH radical, superoxide anion radical and hydroxyl radical) of chitosan derivatives was 2.4–8.3 times higher than that of chitosan. The antibacterial capacity against E. coli and S. aureus of cationic derivatives (HACC derivatives, TMC derivatives, and amidated chitosan bearing imidazolium salts) was more active than only imidazole-chitosan (amidated chitosan). In particular, the inhibition effect of HACC derivatives on E. coli was 15.625 μg/mL. Moreover, the series of chitosan derivatives bearing imidazole acids showed certain activity against MCF-7 and A549 cells. The present results suggest that the chitosan derivatives in this paper seem to be promising carrier materials for use in drug delivery systems.

Noncovalent PEGylation of protein and peptide therapeutics.

Clinical applications of protein therapeutics-an advanced generation of drugs characterized by high biological specificity-are rapidly expanding. However, their development is often impeded by unfavorable pharmacokinetic profiles and largely relies on the use of drug delivery systems to prolong their in vivo half-life and suppress undesirable immunogenicity. Although a commercially established PEGylation technology based on protein conjugation with poly(ethylene glycol) (PEG)-protective steric shield resolves some of the challenges, the search for alternatives continues. Noncovalent PEGylation, which mainly relies on multivalent (cooperative) interactions and high affinity (host-guest) complexes formed between protein and PEG offers a number of potential advantages. Among them are dynamic or reversible protection of the protein with minimal loss of biological activity, drastically lower manufacturing costs, "mix-and-match" formulations approaches, and expanded scope of PEGylation targets. While a great number of innovative chemical approaches have been proposed in recent years, the ability to effectively control the stability of noncovalently assembled protein-PEG complexes under physiological conditions presents a serious challenge for the commercial development of the technology. In an attempt to identify critical factors affecting pharmacological behavior of noncovalently linked complexes, this Review follows a hierarchical analysis of various experimental techniques and resulting supramolecular architectures. The importance of in vivo administration routes, degradation patterns of PEGylating agents, and a multitude of potential exchange reactions with constituents of physiological compartments are highlighted. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.

Selection of an Amino Acid Site with One of the Fastest Cleavage Kinetics by the Endosomal Protease Cathepsin B for Potential Use in Drug Delivery Systems.

On the basis of known published data, six peptide sequences were selected that are potentially capable of being rapidly cleaved by the endosomal protease cathepsin B. For comparison, the cleavage of common linker sequences, polyglycine and polyglycine-serine, by cathepsin B was also studied. Different ends of these peptides were labeled with sulfoCyanine3 and sulfoCyanine5 fluorescent dyes, between which Förster resonant energy transfer (FRET) is possible. The kinetics of cleavage of peptides by cathepsin B was studied on a multimodal plate reader by FRET signal reduction. FKFL and FRRG cleavage sites have been shown to be the most suitable for potential use in various drug delivery systems. These sites are much more efficiently cleaved under slightly acidic conditions of endosomes than at neutral extracellular pH.

Polymicellar-based drug delivery systems for use in nanodentistry

Polymicellar-based drug delivery systems for use in nanodentistry

A Nanotechnological Approach to Exploit and Enhance the Bioactivity of an Extract from Onopordum illyricum L. Leaves.

Plant-derived products have been used for preventive and curative purposes from the ancient era to the present day. Several studies have demonstrated the efficacy of either multicomponent-based extracts, enriched fractions, or isolated bioactives. However, they often display low solubility and bioavailability, chemical instability, poor absorption, and even toxicity, which restrict application in therapy. The use of drug delivery systems, especially nanocarriers, can overcome these physicochemical and pharmacokinetic limitations. In this study, an extract from Onopordum illyricum leaves was produced by maceration in 80% ethanol, characterized by liquid chromatography coupled to mass spectrometry, and formulated in phospholipid vesicles with the aim of exploiting and possibly enhancing its bioactivity for skin delivery. The results showed that phenolic compounds were abundantly present in the extract, especially hydroxycinnamic acid and flavonol derivatives. The extract-loaded vesicles showed small size (<100 nm), high entrapment efficiency (even >90% for most phenolic compounds), and good long-term stability. Moreover, the extract-loaded vesicles exhibited remarkable antioxidant activity, as demonstrated by colorimetric assays and by enhanced reduction of intracellular reactive oxygen species (ROS) levels in cultured skin cells. Hence, our findings support the key role of nanotechnological approaches to promote the potential of plant extracts and strengthen their application in therapy.

Superparamagnetic Iron-Oxide Nanoparticles Synthesized via Green Chemistry for the Potential Treatment of Breast Cancer.

In the emerging field of nanomedicine, nanoparticles have been widely considered as drug carriers and are now used in various clinically approved products. Therefore, in this study, we synthesized superparamagnetic iron-oxide nanoparticles (SPIONs) via green chemistry, and the SPIONs were further coated with tamoxifen-conjugated bovine serum albumin (BSA-SPIONs-TMX). The BSA-SPIONs-TMX were within the nanometric hydrodynamic size (117 ± 4 nm), with a small poly dispersity index (0.28 ± 0.02) and zeta potential of -30.2 ± 0.09 mV. FTIR, DSC, X-RD, and elemental analysis confirmed that BSA-SPIONs-TMX were successfully prepared. The saturation magnetization (Ms) of BSA-SPIONs-TMX was found to be ~8.31 emu/g, indicating that BSA-SPIONs-TMX possess superparamagnetic properties for theragnostic applications. In addition, BSA-SPIONs-TMX were efficiently internalized into breast cancer cell lines (MCF-7 and T47D) and were effective in reducing cell proliferation of breast cancer cells, with IC50 values of 4.97 ± 0.42 μM and 6.29 ± 0.21 μM in MCF-7 and T47D cells, respectively. Furthermore, an acute toxicity study on rats confirmed that these BSA-SPIONs-TMX are safe for use in drug delivery systems. In conclusion, green synthesized superparamagnetic iron-oxide nanoparticles have the potential to be used as drug delivery carriers and may also have diagnostic applications.

Development and evaluation of methotrexate nanocomposites using Β-cyclodextrins/alginate polymers and response surface methodology

β-cyclodextrin and alginate polymers have been extensively investigated for their use in drug delivery systems. β-Cyclodextrin-alginate nanoparticles (CD/Alg) as an innovative drug carrier was the preapared by ionic chelation method. Methotrexate (MTX) as model drug was loaded onto the β-CD/Alg nanoparticles to form MTX-CD/Alg nanocomposites, via ionic interactions. The study was to investigate the changes in independent variables (concentration of CD, Alg and CaCl2) loading efficiency and particle size using 4-levels of CD, 5-levels of Alg and 4-levels of CaCl2. The Optimum nanocomposite has %LE (58.1% and particle size (213 nm). The prepared nanocomposites were chrecterized by powder X-ray diffraction (PXRD), Fourier transform infrared spectroscopy (FTIR), a thermogravimetric analysis (TGA) and a release study. FTIR analysis displayed the drug into nanocomposites. The XRD pattern of MTX-β-CD/Ag nanocomposite suggested a peak at 2θ = 44.6° with the amorphous properties. A novel MTX-CD/Alg nanocomposites was developed. Optimized, characterized, and release studied was performed. These nanocomposites will be prmosing by delivering the drug in powder form

Development of Titanium Surfaces Oxidized by Electrolytic Plasma, for Biomedical Application

Local drug delivery systems used in dental implants need to have uniform pore size distribution, adequate wettability, chemical composition, and biocompatibility. In the present work, titanium was treated by pulsed plasma electrolytic oxidation (PPEO), using 0.025 M sodium dihydrogen phosphate and 0.25 M calcium acetate as electrolytes, aiming at use in drug delivery systems. Pulse with Ton/Toff (width pulse/repetition time) of 50 μs/100 μs or 100 μs/50 μs, duty cycle 0,33, and 0.67, respectively, were used. After treatment, Ca/P ratio, wettability, crystalline phase, pore size and distribution were determined. The average pore size ranged from 1.5 μm to 2.3 μm according to the increase of energy supplied to the system. Pore distributions with lower dispersion were verified for the Ton/Toff condition of 50 μs /100 μs, using a current density of 30 mA/dm2. On the other hand, the 100 μs/50 μs conditions produce larger pores, but with greater dispersion. In general, conditions with lower currents (30 mA/dm2 and 38 mA/dm2) and Ton/Toff ratio = 50/100 were the most appropriate for use in drug delivery systems, due to their size and distribution of uniform pores, greater hydrophilicity, and Ca/P ratio close to desirable (1.67) was obtained.

Nanocellulose-based hydrogels for drug delivery.

Hydrogels, as a class of three-dimensional (3D) polymer networks, are important candidates for drug delivery owing to their high porosity and hydrophilicity. Generally, clinical applications put forward various requirements for drug delivery systems (DDSs), such as low toxic side effects, high biocompatibility, targeting, controllable release, and high drug loading. In recent years, nanocellulose, including cellulose nanocrystals (CNCs) and cellulose nanofibrils (CNFs), has emerged as a promising material for hydrogel-based DDSs. This is due to its high surface area, abundant surface hydroxyl groups that can be easily chemically modified for multifunctionalization, natural origin leading to high biocompatibility and degradability, etc. This review provides a comprehensive overview of the preparation methods for hydrogels based on CNCs/CNFs for use in drug delivery systems, including physical crosslinking and chemical crosslinking. Additionally, various carrier forms such as hydrogel particles, hydrogel films, injectable hydrogels, and sprayable hydrogels are discussed. Key drug delivery parameters including loading and release efficiency as well as responses to different stimuli are also examined in detail. Finally, in view of the subdivision of drug delivery, the opportunities and challenges of nano cellulose based hydrogels were proposed from the perspective of application, and the potential research directions were pointed out.

The Dual Modification of PNIPAM and β-Cyclodextrin Grafted on Hyaluronic Acid as Self-Assembled Nanogel for Curcumin Delivery.

Curcumin is an extract of turmeric (Curcuma longa) which possesses anti-inflammatory, anti-cancer and wound-healing effects and has been used as an active compound in biomedical research for many years. However, its poor solubility presents challenges for its use in drug delivery systems. A modified nanogel delivery system, with PNIPAM and β-cyclodextrin grafted onto hyaluronic acid (PNCDHA), was utilized to enhance the solubility. The polymer was characterized by NMR, and the inclusion complex between curcumin and β-cyclodextrin was confirmed by FTIR. The potential of this PNCDHA polymer complex as a drug delivery vehicle was supported by a curcumin encapsulation efficiency of 93.14 ± 5.6% and the release of encapsulated curcumin at 37 °C. At a concentration of 0.5% w/v in water, PNCDHA nanogels were biocompatible with fibroblast cell line (L929) up to a curcumin concentration of 50 µM. There was a direct concentration between curcumin loading and cellular internalization. A more detailed study of the cellular internalization of PNCDHA nanogel should be considered in order to clarify cellular delivery mechanisms and to assess how its viability as a carrier may be optimized.

Antiparkinsonian Agents in Investigational Polymeric Micro- and Nano-Systems

Parkinson's disease (PD) is a devastating neurodegenerative disease characterized by progressive destruction of dopaminergic tissue in the central nervous system (CNS). To date, there is no cure for the disease, with current pharmacological treatments aimed at controlling the symptoms. Therefore, there is an unmet need for new treatments for PD. In addition to new therapeutic options, there exists the need for improved efficiency of the existing ones, as many agents have difficulties in crossing the blood-brain barrier (BBB) to achieve therapeutic levels in the CNS or exhibit inappropriate pharmacokinetic profiles, thereby limiting their clinical benefits. To overcome these limitations, an interesting approach is the use of drug delivery systems, such as polymeric microparticles (MPs) and nanoparticles (NPs) that allow for the controlled release of the active ingredients targeting to the desired site of action, increasing the bioavailability and efficacy of treatments, as well as reducing the number of administrations and adverse effects. Here we review the polymeric micro- and nano-systems under investigation as potential new therapies for PD.

Injectable Drug Delivery Systems for Osteoarthritis and Rheumatoid Arthritis.

Joint diseases are one of the most common causes of morbidity and disability worldwide. The main diseases that affect joint cartilage are osteoarthritis and rheumatoid arthritis, which require chronic treatment focused on symptomatic relief. Conventional drugs administered through systemic or intra-articular routes have low accumulation and/or retention in articular cartilage, causing dose-limiting toxicities and reduced efficacy. Therefore, there is an urgent need to develop improved strategies for drug delivery, in particular, the use of micro- and nanotechnology-based methods. Encapsulation of therapeutic agents in delivery systems reduces drug efflux from the joint and protects against rapid cellular and enzymatic clearance following intra-articular injection. Consequently, the use of drug delivery systems decreases side effects and increases therapeutic efficacy due to enhanced drug retention in the intra-articular space. Additionally, the frequency of intra-articular administration is reduced, as delivery systems enable sustained drug release. This review summarizes various advanced drug delivery systems, such as nano- and microcarriers, developed for articular cartilage diseases.