Current Drug Delivery - Volume 20, Issue 7, 2023

Background: Osteoarthritis (OA) causes economic, social, and health difficulties in patients. Approximately 10% to 15% of all persons above the age of 60 have some degree of OA. OA is more common in women than in males. Diagnosed OA prevalence varies widely among EU member states, from 2.8% in Romania to 18.3% in Hungary. Introduction: Osteoarthritis (OA) is a slow-progressing, non-inflammatory disorder. This disorder ultimately destroys articular cartilage and other joint components. The main symptoms are stiffness, pain, loss of flexibility, swelling, and bone spurs. Many modifiable and non-modifiable risk factors have been associated with osteoarthritis (OA), including obesity and lack of exercise, genetic susceptibility, bone density, work-related damage, and trauma. Methods: Hydrogels, micro and nano-sized particles, and novel topical gels are the most common examples. Hydrogels are cross-linked polymers with 3-D architecture that can hold water and expand like living tissue. The micro-carriers and nano-based drug delivery systems provide several advantages and may demonstrate prolonged release, controlled release, and higher joint half-life. Results: OA-induced male Lewis rats were injected with celecoxib-loaded PEA microspheres to assess in vivo biocompatibility and degradation. According to the findings of this research, PEA microspheres loaded with celecoxib may be employed as safe delivery of drugs with self-regulating behavior for pain treatment related to knee osteoarthritis. Conclusion: The concept of novel drug delivery systems has shown tangible benefits as a new avenue for precise, safe, high-quality drug delivery for OA treatment. Currently, herbal drugs are also used in osteoarthritis treatment due to their potency and fewer side effects than synthetic drugs. The herbosynthetic approach is a new concept for the delivery of both herbal and synthetic drugs together to exploit their individual beneficial effects while reducing undesirable side effects.

Background: Nanotechnology is rapidly advancing in almost every area, such as the pharmaceutical industry, food industry, nano fabrics, electronics, wastewater treatment, and agriculture. Introduction: Metallic nanoparticles are commonly used in various fields but are especially important in the pharmaceutical industry. Metallic nanoparticles have a size range of 10 nm to 100 nm. Methods: Two techniques are used to synthesize metallic nanoparticles, the top-down approach and the bottom-up approach. These techniques can be synthesized using three different methods: physical, chemical, and biological. Chemical methods include coprecipitation, reduction, sonochemical, solvothermal, and others, while physical methods include discharge, milling, and ion implantation. Biological methods include plants and their extracts, agricultural wastes, microorganisms, and seaweeds. Scanning electron microscopy, transmission electron microscopy, dynamic light scanning, and other techniques are used to characterize them. Results: All metallic nanoparticles are biocompatible and have special optical, electrical, magnetic, and chemical properties. They are used in various industries, including the pharmaceutical industry as an anticancer agent, antibacterial, antifungal, antioxidant, antidiabetic, and biosensors. Gold, silver, iron oxide, zinc oxide, platinum, copper oxide, and palladium nanoparticles are the most common metal nanoparticles used in the pharmaceutical industry. Monometallic and multimetallic nanoparticles are broadly classified under this. Conclusion: This article focuses on the major metallic nanoparticle groups, including synthesis, applications, case studies, toxicity, regulatory aspects and innovative approaches to metallic nanomaterials.

Nanosponges are colloidal and crosslinked nanocarriers consisting of a solid mesh-like network with nanocavities to encompass various types of substances like antineoplastic, proteins, peptides, volatile oil, DNA and then incorporated into topical medications that are mainly formulated such as gels, creams, lotions, ointments, liquid and powders etc. for topical drug delivery system. In the polymeric construction of nanosponges, the release of enthalpy-rich water molecules accounts for high complexation efficiency for different molecular substances. The benefits of nanosponges involve the extended and controlled release of encapsulated particles with excellent competence and great stability. Nanosponges assume a significant part in new varieties of medicaments, beautifiers, farming, horticulture, high atomic weight containing proteins, innovative fire retardants, gas transporters, and water filters. Nanosponges are a novel technology that offers controlled and targeted drug delivery by various routes like oral, parenteral, and topical routes. Nanosponges are an effective transporter for biologically active ingredients; therefore, it is broadly employed in anti-cancer, antiviral, antiplatelet, and antilipidemic therapy. This review article gives attention to the general introduction, merits and demerits, classification, characteristic features, procedures for developing nanosponges, and numerous factors which affect nanosponge formulation, evaluation parameters, and applications in the medicinal industry.

Cancer is the world's fifth-most significant cause of related death and the second most commonly diagnosed malignancy among women and men. Some of its types, like brain cancer, colon cancer, and breast cancer, are threatened and considered fatal. These cancers are more prevalent in developed and underdeveloped countries. Still, doxorubicin is considered a gold standard drug and the only molecule used in multiple types of cancer. However, the toxicity and biopharmaceutical hindrances like poor solubility, poor permeability, and high in vivo fate of drug cause low systematic circulation. The creation of a multifunctional nanocarrier for targeted medication delivery that can transport and accumulate drugs at cancer sites should help to lessen the likelihood of side effects. These nanocarriers improve the targetability of infected tissue and the therapeutic circulation of drugs. Hence, the present review focused on the improved targetability of doxorubicin using different nanocarriers and its possible outcomes in different types of cancer. Moreover, the prior art also discussed various challenges and prospects of improved doxorubicin delivery and its therapeutic outcomes.

Background: Paclitaxel (PTX), voted as the promising natural medicine molecule, is widely used in the treatment of cancers. Nevertheless, its clinical application is strictly limited by its poor water solubility. Objective: CP-MEs (Paclitaxel-coix seed oil coloaded microemulsion), a small-sized self-emulsifying nanoemulsion formed from a combination of PTX and coix seed oil (CSO), was developed in order to improve the solubility of paclitaxel and enhance anti-cervical cancer efficacy in vitro. CSO was selected as the oil phase to replace conventional organic solvents and achieve a synergistic anti-tumor effect with paclitaxel. Methods: Pseudoternary phase diagram was applied to the study of CP-MEs formulation. CP-MEs were prepared and characterized by transmission electron microscopy (TEM) and dynamic light scattering (DLS). The encapsulation efficiency and drug loading efficiency (EE and LE) were detected by HPLC. MTT was adopted to evaluate the cytotoxicity of CP-MEs against HeLa cells. The cellular uptake and apoptotic ratio of CP-MEs were evaluated by flow cytometry. Notably, HeLa 3D tumor spheroid was adopted to evaluate tumor permeability of different size microemulsions as the model. Results: The best self-emulsifying ability was exhibited by HS 15: PEG 400 combination. The appearance of CP-MEs was clear and transparent, which exhibited a small size (30.28 ± 0.36) and a slight negative surface charge (-4.40 ± 1.13) mV. The EE and LE of CP-MEs were 98.80% and 0.978%, respectively. The cumulative release rate within 48 h of the CP-MEs was 80.21%. In cellular studies, the uptake of fluorescein isothiocyanate (FITC) labeled CP-MEs (FITC/C-MEs) was 17.86-fold higher than the free FITC group, leading to significant synergistic anticancer activity in terms of cytotoxicity and apoptosis induction in vitro. The apoptotic rate of CP-MEs treated was 1.70-fold higher than PTXtreated. Notably, the penetration of CP-MEs in the HeLa 3D tumor sphere model was enhanced, which was related to deeply penetrated microemulsion of small size mediated at the tumor site. Conclusion: With the advantage of the small-sized self-emulsifying system, CP-MEs hold great potential to become an efficient nano drug delivery system for cervical cancer treatment in the clinic.

Background: Numerous formulations have been utilized in the cosmetic and pharmaceutical industries to effectively deliver bioactive ingredients. Methods: We selected a well-known liposomal formulation of bilayer lipid vesicles composed of ceramide NP. Ethosomes contain hydrophilic vanillic acid or lipophilic α-bisabolol, and their physicochemical properties were evaluated. Vanillic acid is encapsulated in the aqueous core while α-bisabolol is engaged with the lipid phase. The formulation was prepared by the high-pressure homogenization method at 800 bar for 5 min. The particle size, polydispersity index and zeta potential of the ethosome dispersion were analyzed by dynamic light scattering. In order to measure the skin absorption efficiency from artificial skin, an in vitro assay was performed using the Franz diffusion cell method for 24 hours. In addition, ultracentrifuges for encapsulation efficiency, dialysis membranes for active ingredient release, and low-temperature transmission electron microscopy (TEM) to evaluate the morphology of vesicles were utilized. Results: The particle size of the ethosome containing ceramide NP and vanillic acid was in the range of 80 ~ 130 nm, whereas the particle size of the ethosome containing ceramide NP and α-bisabolol was 150 ~ 170 nm. In the vanillic acid-containing ethosome, increasing the amount of ceramide NP decreased the particle size, whereas the size of the α-bisabolol ethosome did not change. The stability of the prepared ethosome did not change significantly for 4 weeks at 25°C, 4°C, and 45°C. The skin absorption efficiency of ceramide NP and vanillic acid-containing ethosome was increased by about 15% compared to the control group, whereas the ethosome containing α-bisabolol and ceramide NP showed slightly higher skin absorption efficiency than the control group. In addition, encapsulation efficiency evaluation, active ingredient release measurement and cryo-TEM were taken. Conclusion and Perspective: Based on the results of these studies, we suggest that ethosome formulations containing ceramide NP can be widely used in the cosmetic industry together with other cosmetic formulations.

Background: The combinatorial use of anticancer drugs, dual or multiple, with a specific nanocarrier is one of the most promising attempts in drug delivery. The current work reports potassium contained graphene oxide (K-GO) as a nanocarrier in the drug delivery system of two anticancer drugs, gefitinib (GEF) and camptothecin (CPT), simultaneously. Methods: To characterize K-GO, K-GO-related single and combined drug systems, different techniques have been performed and studied using the following spectroscopic tools, such as Thermo Gravimetric Analysis (TGA 4000), UV–visible spectroscopy, Raman spectroscopy, and Transmission electron microscopy (TEM). The in vitro cytotoxicity tests of K-GO, single drug system, and the combined drug system were also performed in the human breast cancer MDA-MB-231 cells. Results: The release profile of the dual drug conjugates grafted onto the surface of K-GO was found to be up to 38% in PBS solution over 72 hours. The percentage of MDA-MB-231 cell viability was about 18% when treated with K-GO-GEF-CPT combined system; for K-GO, K-GO-GEF, and K-GO-CPT, the cell viability was 79%, 31%, and 32%, respectively. Conclusion: We studied the loading, release, and delivery of two anticancer drugs onto the fluorescent nanocarrier. Features, such as superb aqueous solubility, excellent biocompatibility, richness in potassium, and fluorescent nature, which can monitor the delivery of drugs, make them a promising nanocarrier for single or multiple drug delivery. Furthermore, our novel findings revealed that the loading capacity and cytotoxicity of the combined drug-loaded system are superior to the capacity of the individual drug system for human breast cancer cells.

Background: Cationic lipids can be used as nonviral vectors in gene delivery therapy. Most cationic lipids contain quaternary ammonium that can bind to negative phosphates of the plasmid. In this study, sulfonium—a trialkylated sulfur cation was adopted in the synthesis of a series of cationic lipids which were evaluated for their ability to function as gene delivery vectors. Methods: The sulfonium lipids were synthesized by condensing cyclic thioether and aliphatic carbon chains with ethoxy linkage and the structure was characterized by NMR and mass. The DNA condensing abilities of sulfonium lipids were evaluated using a gel retardation experiment. Sulfonium lipids/ DNA condensates were measured for particle size and Zeta potential. The cytotoxicity of sulfoniums was evaluated with the MTT assay. The intracellular uptake of sulfonium lipid/DNA complexes was observed with a fluorescence microscope. Results: The results showed that the sulfonium head can effectively bind to the phosphate of DNA. When the S/P ratio is larger than 10/1, sulfonium lipids with longer carbon chains can completely condense DNA to form a nanoparticle with particle size ranging from 135 nm to 155 nm and zeta potential ranging from 28 mV to 42 mV. The IC50 of sulfonium lipids on HepG2 cells ranged from 2.37 μg/mL to 3.67 μg/mL. Cellular uptake experiments showed that sulfonium lipids/DNA condensate can be taken into cells. Conclusion: Sulfonium lipids can effectively condense DNA and transfer DNA into cells. The sulfonium compound is worth further development to reduce the cytotoxicity and increase the transfection rate as gene vectors.

Introduction: The goal of this study was to see if ascorbic acid grafted polylactic glycolic acid-b-polyethylene glycol nanoparticles (PLGA-b-PEG NPs) might boost the carrying or transport capacity of rivastigmine(RSM) to the brain via choroid plexus Sodium-dependent vitamin C transporter 2 (SVCT2 transporters). The IR and 1H NMR, were used to characterise the PLGA-b-PEG copolymer. Methods: Nanoprecipitation method was used to make PLGA-b-PEG NPs. To promote SVCT2- mediated transportation of ascorbic acid (Asc) into the brain, PLGA-b-PEG NPs of acceptable size, polydispersity, and drug loading were bound with ascorbic acid (PLGA-b-PEG-Asc). When compared to PLGA-b-mPEG NPs, the surface functionalization of NPs with ascorbic acid dramatically improved the cellular uptake of NPs in SVCT2 expressing NIH/3T3 cells. Radial Arm Maze Test, and Acetylcholinesterase (AChE) activity in scopolamine-induced amnetic rats were used to assess in vivo pharmacodynamic effectiveness. Results: In vivo pharmacodynamic tests revealed that drug loaded PLGA-b-PEG-Asc NPs had much greater therapeutic and sustained activity than free drugs, and PLGA-b-mPEG NPs to the brain. Conclusion: As a consequence, the findings revealed that using ascorbic acid grafted PLGA-b-PEG NPs to deliver bioactives to the brain is a potential strategy.

Background: Irinotecan is a promising antitumor agent approved by FDA for intravenous use in colon cancer treatment either alone or in combination. It is a topoisomerase inhibitor and by blocking the topoisomerase-I enzyme, it causes DNA damage and results in cell death. However, it lacks selectivity and specificity for tumor cells, resulting in systemic toxicity. Thus, it is essential to reduce its side effects and improve therapeutic efficacy. Objective: The study aimed to improve the therapeutic efficacy and minimize the toxic effects of irinotecan by developing a fullerene functionalized biotin drug delivery system and adsorbing irinotecan on the surface of the functionalized fullerene-biotin complex. Methods: Fullerene (C60) has been observed as a potential drug delivery agent and the aminefunctionalized C60-NH2 was synthesized by functionalizing ethylenediamine on the surface of C60. The PEI functionalized C60 was further synthesized by polymerization of aziridine on the surface of C60- NH2. Biotin was attached by an amide linkage to C60-PEI and the anti-colon cancer drug irinotecan (IRI) was encapsulated (C60-PEI-Biotin/IRI). The C60-PEI-Biotin/IRI was characterized and evaluated for in vivo anti-colon cancer activity in rats and the results were compared with the parent drug irinotecan. Results: The results showed that C60-PEI-Biotin/IRI conjugate had a controlled release profile according to in vitro HPLC studies. Moreover in vivo anti-tumor studies suggested that the conjugate proved to be less toxic to vital organs and had high efficacy towards tumor cells. Statistical studies confirmed less tumor index and tumor burden in the case of conjugate when compared to irinotecan. Conclusion: It is hypothesized that the conjugate (C60-PEI-Biotin/IRI) could cross the cell membrane easily through overexpressed biotin receptors on the cell surface of colon cancer cells and showed better efficacy and less toxicity in comparison to IRI in the colon cancer rat model.

Background: A combination of antibiotics, including metronidazole (MET), ciprofloxacin (CIP), and minocycline (MINO), has been demonstrated to disinfect bacteria in necrotic teeth before regenerative processes. It has been presented clinically that antibiotic pastes may drive to possible stem cell death, creating difficulties in removing from the canal system, which can limit the regenerative procedure. This study was designed to (1) synthesize nanofibrous webs containing various concentrations of different medicaments (triple, double, and calcium hydroxide, Ca(OH)2), and (2) coat the electrospun fibrous gutta-percha (GP) cones. Methods: Poly(vinylpyrrolidone) (PVP)-based electrospun fibrous webs were processed with low medicament concentrations. Scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX), and X-ray photoelectron spectroscopy (XPS) were carried out to investigate fiber morphology and antibiotic incorporation, and characterize GP-coated fibrous webs, respectively. The chemical and physical properties of dentine were determined via fourier transform infrared spectroscopy (FTIR) and Nano-SEM, respectively. The antimicrobial properties of the different fibrous webs were assessed against various bacteria by direct nanofiber/bacteria contact. Cytocompatibility was measured by applying the MTT method. Results: The mean fiber diameter of the experimental groups of medicament-containing fibers ranged in the nm scale and was significantly smaller than PVP fibers. EDX analysis confirmed the presence of medicaments in the nanofibers. XPS analysis presented a complete coating of the fibers with GPs; FTIR and Nano-SEM showed no chemical and physical configuration of intracanal medicaments on the dentine surface. Meanwhile, nanofibrous webs led to a significant reduction in the percentage of viable bacteria compared to the negative control and PVP. Conclusion: Our findings suggest that TA-NFs, DA-NFs, and Ca(OH)2)-NFs coated GP cones have significant potential in eliminating intracanal bacteria, having cell-friendly behavior and clinical usage features.

Background: Chemoresistance continues to limit the recovery of patients with cancer. New strategies, such as combination therapy or nanotechnology, can be further improved. Objective: In this study, we applied the computational strategy by exploiting two databases (CellMiner and Prism) to sort out the cell lines sensitive to both anti-cancer drugs, paclitaxel (PTX) and dihydroartemisinin (DHA); both of which are potentially synergistic in several cell lines. Methods: The combination of PTX and DHA was screened at different ratios to select the optimal ratio that could inhibit lung adenocarcinoma NCI-H23 the most. To further enhance therapeutic efficacy, these combinations of drugs were incorporated into a nanosystem. Results: At a PTX:DHA ratio of 1:2 (w/w), the combined drugs obtained the best combination index (0.84), indicating a synergistic effect. The drug-loaded nanoparticles sized at 135 nm with the drug loading capacity of 15.5 ± 1.34 and 13.8 ± 0.56 corresponding to DHA and PTX, respectively, were used. The nano-sized particles improved drug internalization into the cells, resulting in the significant inhibition of cell growth at all tested concentrations (p < 0.001). Additionally, α-tubulin aggregation, DNA damage suggested the molecular mechanism behind cell death upon PTX-DHA-loaded nanoparticle treatment. Moreover, the rate of apoptosis increased from approximately 5% to more than 20%, and the expression of apoptotic proteins changed 4 and 3 folds corresponding to p-53 and Bcl-2, respectively. Conclusion: This study was designed thoroughly by screening cell lines for the optimization of formulations. This novel approach could pave the way for the selection of combined drugs for precise cancer treatment.