Cyclodextrins (CDs) have revolutionized the pharmaceutical industry with their ability to enhance the stability, solubility, and bioavailability of a wide range of active substances. These cyclic oligosaccharides, with a unique hydrophilic exterior and hydrophobic cavity, form inclusion complexes with poorly soluble drugs, improving their pharmacokinetic profiles and therapeutic efficacy. This review explores the multifaceted roles of cyclodextrins in pharmaceutical formulations, ranging from oral, ophthalmic, parenteral, and topical applications to their emerging use in targeted therapies, gene delivery, and treatment of neurodegenerative, cardiovascular, and infectious diseases. Cyclodextrins not only improve drug solubility and controlled release but also reduce toxicity and side effects, leading to safer and more effective treatments. Recent advancements, such as cyclodextrin-based nanoparticles, offer promising pathways for cancer therapy, chronic disease management, and personalized medicine. As research continues, cyclodextrins remain at the forefront of innovation in drug delivery systems, ensuring better patient outcomes and expanding the possibilities of modern therapeutics.
Cyclodextrins (CDs) have largely been investigated during the last decades for their outstanding properties, such as biocompatibility and biodegradability, with wide applications in the pharmaceutical field, among which the formation of inclusion complexes (ICs) with natural or synthetic lipophilic compounds. This review prioritizes the research of recent years (2022–2025), being focused on (1) systematization of the research of ICs based on the structure of the secondary metabolite, namely (i) polyphenols (PPs), (ii) terpenes and terpenoids (TTs), and (iii) alkaloids (Alks); (2) for each type of inclusion complex, the following aspects have been discussed: benefits of complexation, composite materials, and in vitro/in vivo and theoretical studies; and (3) pharmacokinetics and pharmacodynamics, risks, limitations, and perspectives of cyclodextrin inclusion complexes with secondary metabolites.
The current strategy for treating osteomyelitis includes surgical procedures for complete debridement of the formed biofilm and necrotic tissues, systemic and oral antibiotic therapy, and the clinical use of cements and three-dimensional scaffolds as bone defect fillers and delivery systems for therapeutic agents. The aim of our research was to formulate a low-cost hybrid nanoparticulate biomaterial using poly(lactic-co-glycolic acid) (PLGA), in which we incorporated the therapeutic agent (ciprofloxacin), and to deposit this material on titanium plates using the matrix-assisted pulsed laser evaporation (MAPLE) technique. The deposited material demonstrated antibacterial properties, with all analyzed samples inhibiting the growth of tested bacterial strains, confirming the release of active substances from the investigated biocomposite. The poly(lactic-co-glycolic acid)-ciprofloxacin (PLGA-CIP) nanoparticle scaffolds displayed a prolonged local sustained release profile over a period of 45 days, which shows great promise in bone infections. Furthermore, the burst release ensures a highly efficient concentration, followed by a constant sustained release which allows the drug to remain in the implant-adjacent area for an extended time period.
A new bicomponent hybrid material was obtained by encapsulating quercetin in PLGA using solvent evaporation method. The morphological aspects of the samples were established by scanning electron microscopy (SEM). Particle size distribution was determined by dynamic light scattering (DLS), numerical distribution showing that the particles are micrometric, with two granulometric intervals: [385-479] nm and [662-918] nm. Morphology was typical for PLGA, spherical one; the obtained particles are porous with micrometric pores. Zeta potential (ZP, -4.84mV) showed that the particles have electronegative surface charge. The loading efficiency was determined spectrophotometric and it was 18.3% in the mentioned synthesis conditions.
The study evaluates the osteointegration of hydroxyapatite (HAp) and hydroxyapatite-titanium (HApTi) biocomposites implanted in the femurs of rabbits. The biocomposites were fabricated using powder metallurgy and subjected to a two-step sintering process. Scanning electron microscopy (SEM) was employed to analyze the morphology, while mesenchymal stem cells were cultured to assess cytotoxicity and proliferation. In vivo experiments involved the implantation of HAp in the left femur and HApTi in the right femur of twenty New Zealand white rabbits. Computed tomography (CT) scans, histological, immunohistochemical, and histomorphometric analyses were performed to assess bone density and osteoblast activity. Results demonstrated that HApTi implants showed superior osteointegration, with higher peri-implant bone density and increased osteoblast count compared to HAp implants. This study concluded that HApTi biocomposites have potential for enhanced bone healing and stability in orthopedic applications.
This study explores the antibacterial efficacy and cytotoxicity of ciprofloxacin-functionalized bioceramic implants. We synthesized hydroxyapatite-ciprofloxacin (HACPXCS) composites and applied them to titanium substrates (Ti-HA-CPX), evaluating their performance in vitro against Staphylococcus aureus (ATCC 25923) and Escherichia coli (ATCC 25922). Antibacterial activity was assessed using the Kirby-Bauer disc diffusion method, while cytotoxicity was tested using mesenchymal stem cells. The results demonstrated that Ti-HA-CPX exhibited superior antibacterial activity, with inhibition zones of 33.5 mm (MIC 0.5 µg/mL) for Staphylococcus aureus (ATCC 25923) and 27.5 mm (MIC 0.25 µg/mL) for Escherichia coli (ATCC 25922). However, Ti-HA-CPX showed moderate cytotoxicity (80% cell viability). HACPXCS composites, whether chemically synthesized or mechanically mixed (HACPXMM), also displayed significant antibacterial activity, but with cytotoxicity ranging from low to moderate levels. Molecular docking studies confirmed strong binding affinities between ciprofloxacin and bacterial proteins, correlating with enhanced antibacterial efficacy. These findings suggest that Ti-HA-CPX composites offer a promising approach for single-stage surgical interventions in treating chronic osteomyelitis and infected fractures, balancing antibacterial effectiveness with manageable cytotoxicity.
NAD+ is known classically as a metabolite that participates in catabolic and anabolic pathways throughout the metabolism that is taught to students in introductory biochemistry courses. However, non-classical studies starting over a decade ago found that NAD+ is also involved in higher order functions, in part because of its involvement in the activation of SIRTs and the support of the mitochondrial unfolded protein response. Many studies since have suggested that NAD+ is involved in an extensive spectrum of human pathologies, including neurodegenerative disorders, cardiomyopathy, obesity, and diabetes, Further, healthy aging and longevity appear to be closely related to NAD+ and its related metabolites, including NAR and NMN. Together, these studies show that this system has value as a dietary supplement to improve general health overall, as well as mitigating specific disease conditions. Accordingly, many are now recommending the consumption of materials in this system as dietary supplements. Nicotinamide riboside (NAR) appears to have special value in this regard. It appears to be better tolerated than other molecules in this system, as well as better pharmacodynamics and greater potency. Unfortunately, NAR is a reactive molecule, often unstable during its manufacturing, transport, and storage. Indeed, HPLC analyses of many commercial samples of NAR shows that they contain substantial amounts of material that are not, in fact, NAR. In some of these commercial preparations, NAR is a minority component. Therefore, more stable derivatives of NAR that are easily converted upon consumption into NAR are therefore desired. Recently work related to prebiotic chemistry provided the borate derivative of NAR. NARB is considerably more stable than NAR itself. However, immediately upon consumption, the borate dissociates from NARB, and is lost in the body through dilution and binding to other species, notably carbohydrates such as fructose and glucose. The NAR left behind is expected to behave pharmacologically in ways identical to NAR itself. This review provides a comprehensive summary (through Q1 of 2023) of literature that makes the case for the consumption of NAR as a dietary supplement. It then summarizes the challenges of delivering quality NAR to consumers using standard synthesis, manufacture, shipping, and storage approaches. It concludes by outlining the advantages of NAR-borate in these processes.
In recent years, the polyphenolic compounds profile of plants has been intensively studied. These compounds protect the body against oxidative stress and certain diseases such as diabetes and cancer, where the antioxidant efficiency of the defence system is low. The plant material (harvested from Romania) was analysed for polyphenols and flavonoids using thin layer chromatography (TLC) and high-performance liquid chromatography (HPLC) coupled with photo diode array and mass spectrometer. The polyphenols/flavonoids (caffeic acid, chlorogenic acid, p-coumaric acid, protocatechuic acid, rutin and quercetin) were identified and quantified in different part of the plants (flower, leaf, stem and roots for Dipsacus laciniatus and both roots and leaves for Armoracia rusticana). The least amount of polyphenols were found to be as expected in the root part of Dipsacus laciniatus. This was also sustained by the further UHPLC-MS analysis. The results revealed that the flower extract has the highest radical scavenging activity with 87.43% followed by the leaf extract with 86.63%, the stem extract with 83.54% and the root extract with 78.17%. Higher concentrations of p-Coumaric acid and ferulic acid were identified in the Armoracia rusticana samples whereas the Dipsacus laciniatus samples contained higher concentrations of both protocatechuic acid and chlorogenic acid. The results of the present study revealed that the methanolic extracts of both Dipsacus laciniatus and Armoracia rusticana , can be considered an effective source of antioxidant compounds.
Many studies have suggested that the oxidized form of nicotinamide adenine dinucleotide (NAD+) is involved in an extensive spectrum of human pathologies, including neurodegenerative disorders, cardiomyopathy, obesity, and diabetes. Further, healthy aging and longevity appear to be closely related to NAD+ and its related metabolites, including nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN). As a dietary supplement, NR appears to be well tolerated, having better pharmacodynamics and greater potency. Unfortunately, NR is a reactive molecule, often unstable during its manufacturing, transport, and storage. Recently, work related to prebiotic chemistry discovered that NR borate is considerably more stable than NR itself. However, immediately upon consumption, the borate dissociates from the NR borate and is lost in the body through dilution and binding to other species, notably carbohydrates such as fructose and glucose. The NR left behind is expected to behave pharmacologically in ways identical to NR itself. This review provides a comprehensive summary (through Q1 of 2023) of the literature that makes the case for the consumption of NR as a dietary supplement. It then summarizes the challenges of delivering quality NR to consumers using standard synthesis, manufacture, shipping, and storage approaches. It concludes by outlining the advantages of NR borate in these processes.
Osteomyelitis continues to be a major concern when orthopedic surgery is performed. Orthopedic infections have an incidence of 5% to 10% but their management proves to be quite difficult due to both biofilm formation and limited access of the drug to the infected area when systemic treatment is employed. The aim of the study was to optimize the synthesis process of a gentamicin loaded poly(-lactic-co-glycolic) acid (PLGA) based biodegradable composite by varying parameters that affect both efficiency encapsulation and nanoparticle size. Furthermore, a kinetic study was conducted to study the biodegradation process of the polymer. Gentamicin loaded PLGA nanoparticles were obtained using the double emulsion technique which allows the variation of several factors such as gentamycin concentration, PLGA concentration, buffer concentration and stirring speed. Out of the four factors evaluated, gentamicin concentration had the highest impact on both encapsulation efficiency and nanoparticle size. A few relevant interactions between factors were also registered.
The aim of our study was to synthesize a biocomposite material using a natural polymer (collagen), hydroxyapatite and ciprofloxacin. We used Fourier-transform infrared spectroscopy (FT-IR), dynamic light scattering (DLS), high performance liquid chromatography (HPLC-DAD) and scanning electron microscopy (SEM) for the physico-chemical characterization and we determined its antibacterial activity against Staphylococcus aureus Rosenbach (S. aureus), Pseudomonas aeruginosa (Schroter) Migula (P. aeruginosa), Klebsiella pneumonia (Schroter) Trevisan (K pneumoniae) and Escherichia coli (Migula) Castellani and Chalmers (E. coli). The release profile of the ciprofloxacin chemisorbed in the material was also studied, and we found that the release was sustained for 30 days.
This experimental study was aimed at assessing the total polyphenol and flavonoid content of Tragopogon pratensis (folium) vegetal extract and evaluating the histopathological status of mice with liver problems and diabetes during therapy with 20% hydroalcoholic extract of T. pratensis (folium) . The diabetes in mice was induced by single intraperitoneal (i.p.) dose of 180 mg/kg b.w. streptozotocin. The experiment involved two congtrol groups: the first (I) group consisted of mice with normal pancreatic function; the second (II) group consisted of mice with experimentally induced diabetes. The third (III) group of mice with experimentally induced diabetes was treated with T. pratensis extract at a dose of 150 mg/kg b.w.. The first and second groups were not treated, while the third group received daily the established medication once a day, in the morning at the same time (9 a.m), for five weeks. The obtained results showed that the administration of T. pratensis tincture triggers the hepatic regenerative processes, restores functional activity of the liver, and positively influences functionality of the pancreas. The molecular docking analysis supports results of the experimental study.
Herbal extracts with antimicrobial potential represent an important research directive, in the current medical world, aiming to isolate active components, to develop new chemotherapeutic agents with applicability in the treatment or use as adjuvant therapy in infectious states. Antimicrobial properties of plants are conferred by their ability to synthesize certain secondary metabolites with relatively complex structures. The last century has been marked by sustained efforts to search for new natural compounds with antibacterial therapeutic properties, due to the gradual reduction in the number of effective allopathic antibiotics and the toxic effects of antibiotic residues. Numerous in vitro studies have shown that plants have antibacterial efficacy, discovering the importance of little-studied natural resources in this regard, as being effective in fighting against bacterial resistance and destroying bacterial agents. In this study, the antibacterial effect of the fresh onion and garlic juice was compared to the antibiotics of choice, using the diffusimetric agar method. Both plant products tested have antibacterial effect, the bacterial species being classified as sensitive to their action. The molecular docking method helps us to see the type of interaction between ligands and targets, allicin having no common binding site with antibiotics of choice.
Dorycnium herbaceum (DH) is a perennial herb or small shrub 10-80 cm high, which can be found in Central and Southeastern Europe. It is a little studied plant, which is known to have antibacterial and antifungal effect. In the present study we determined by spectrophotometric methods the total polyphenolic, flavonoidic, carotenic and chlorophyllic content of DH species, comparative to the bilberry. We also monitored the status of antioxidant enzymes using mice with oxidative stress induced by streptozotocinic diabet. For the induction of diabetes we used Swiss albino mice to which we injected streptozotocin intraperitoneally at a single dose of 180 mg / kg b.w.. The results showed that both chemical composition tinctures contain appreciable amounts of polyphenols, the highest content starring DH tincture species, but bilberry fruits have higher content of flavonoids, carotene and chlorophyll. Both plant extracts regulate the status of antioxidant enzymes, DH having superior efficacy.
In attempt to avoid prosthetic problems and possible side effects that may occur in long-term bisphosphonate treatment, a solution commonly studied in recent years is local bisphosphonate release. Thus, a higher dose can be administered in the region of interest with positive effects on reduction bone loss in the periprosthetic area, but especially on osteointegration reduction time and acceleration of prosthesis component secondary fixation. On the other hand, stable fixation is also achieved in the case of osteoporotic bone. In the present paper, we have proposed to obtain implant type structures by deposition of alendronate-hydroxyapatite compositions (HA-AL) on titanium metal substrates. The deposition of the composite directly on the metallic component was accomplished by pulsed laser evaporation technique (MAPLE).
There is an increased interest in developing biocomposite implants with high biocompatibility in order to be used as grafts or prostheses in orthopedic surgery. The purpose of the study was to determine the biocompatibility of titanium implants coated with synthesized hydroxyapatite-alendronate composites. The implants were obtained using Matrix Assisted Pulsed Laser Evaporation technique (MAPLE). The hydroxyapatite-alendronate composites were synthesized using the wet precipitation method. Immunofluorescence microscopy showed that composites support mesenchymal stem cells (MSCs) adhesion. Bone cells as well as human MSCs adhere to hydroxyapatite (HA)-based thin films obtained by matrix assisted laser deposition onto titanium. Alendronate doping into the films increased the number of cell-biomaterial focal points as compared to HA only. Thus, the synthesis of hydroxyapatite-alendronate composite (HA-AL) may be considered a viable solution for including the bisphosphonate on the surface of metallic prosthetic components used in orthopedics.
Bisphosphonates are medicines used to inhibit osteoclastic activity in a number of bone diseases (Paget's disease, osteoporosis, hypercalcemia, primary and secondary hyperparathyroidism, bone metastases). Following in vitro release studies, crystalline hydroxyapatite (HA) was found to be a stable phase in contact with the release medium, and alendronate (AL) bound to HA by the synthesis process was slowly released from the metallic component (titanium) into the release medium for 10 days. Hydroxyapatite after implantation produces chemical species that support the adhesion of the implant to the surrounding tissue forming a functional connective structure. Thus synthesis of the HA-AL composite can be considered as a viable solution for the inclusion of bisphosphonate on the surface of metallic prosthetic components used in orthopedics.
Tamarix ramosissima (Tamaricaceae) is a small tree that grows spontaneously in Europe and Asia, being considered an invasive species in geographical areas with warm climates. The chemical composition is partially elucidated, being empirically used for antiinflammatory, analgesic, antibacterial and antioxidant effect. Our study aimed to evaluate the total polyphenol and flavonoid content of vegetal extracts and to test in vivo antioxidant therapeutic effect of it, comparative with Vaccinium myrtillus, using streptozotocin-induced diabetic mice. After five weeks the animals were sacrificed and we determined erythrocyte activities of superoxide dismutase, glutathione peroxidase, glutathione reductase and level of lipid peroxides as thiobarbituric acid reactive substances. Antioxidant enzymes had highest activities in mice treated with T. ramosissima extract and the level of lipid peroxides was the lowest. The tested extract had higher content of polyphenols comparative with V. myrtillus. Our results sustain the efficiency of T. ramosissima extracts on normalizing the effects of oxidative stress in diabetes.
The main objective of this study was to synthesize hydroxyapatite-ciprofloxacin composites using a chemical precipitation method and to evaluate the properties and in vitro release profile of the drug from the hydroxyapatite-ciprofloxacin composites. Composite characterization was achieved by FT-IR, XRD and DLS. Ciprofloxacin determination was accomplished by HPLC, resulting in good incorporation efficiency of the drug (18.13 %). The in vitro release study (Higuchi model C = K t(1/2) and Ritger-Peppas model, C = K t(0.6)) showed a diffusion-controlled mechanism. The antibacterial activity showed that the bacterial growth - inhibition zones were approximately equal for the synthesis composites and for the mechanical mixture on the Staphylococcus aureus germ. The use of hydroxyapatite, which is a biocompatible, bioactive and osteoconductive material, with ciprofloxacin, which has good antibacterial activity in this composite, makes it suitable for the development of bone grafts. Furthermore, the synthesis process allows a slow local release of the drug.
Plant extracts with antimicrobial potential are an important research directive in the current medical world, aiming to isolate active components in order to develop new chemotherapeutic agents that can be used in the treatment of various infectious disease. In the present study we determined the content of polyphenol carboxylic acids and flavonoids for two vegetal extracts, by means of TLC, GC-MS and HPLC techniques. Antimicrobial activity was determined on five bacterial species by performing agar diffusion method, using discs impregnated with standard antimicrobial substances and tested plant extracts. Our results showed that the alcoholic extracts Tragoponis pratensis folium and Myrtilli fructus contain polyphenolic compounds and had antimicrobial effect on a wide range of microorganisms (gram positive and negative).