Drug Delivery Formulations Research Articles

Graphene quantum dot formulation for cancer imaging and redox-based drug delivery

This work develops a new multifunctional biocompatible anticancer nanoformulation to provide targeted image-guided cancer-selective therapeutics. It consists of three active covalently bound components: (1) biocompatible nitrogen-doped graphene quantum dots (GQDs) as a multifunctional delivery and imaging platform, (2) hyaluronic acid (HA) unit targeted to the CD44 receptors on a variety of cancer cells, and (3) oxidative stress-based cancer-selective ferrocene (Fc) therapeutic. The biocompatible GQD platform synthesized from glucosamine exhibits high-yield intrinsic fluorescence. It is utilized for tracking Fc-GQD-HA formulation in vitro indicating internalization enhancement in HeLa cells targeted by the HA over non-cancer HEK-293 cells not overexpressing CD44 receptor. Fc-GQD-HA, non-toxic at 1 mg/mL to HEK-293 cells, induces cytotoxic response in HeLa enhanced over time, while therapeutic ROS generation by Fc-GQD-HA is ~3 times greater than that of Fc alone. This outlines the targeted delivery, imaging, and cancer-specific treatment capabilities of the new Fc-GQD-HA formulation enabling desired cancer-focused nanotherapeutic approach.

Artificial Intelligence in Pharmacy

Abstract: Artificial intelligence (AI) focuses in producing intelligent modelling, which helps in imagining knowledge, cracking problems and decision making. Recently, AI plays an important role in various fields of pharmacy like drug discovery, drug delivery formulation development, polypharmacology, hospital pharmacy, etc. In drug discovery and drug delivery formulation development, various artificial neural networks (ANNs) like deep neural networks (DNNs) or recurrent neural networks (RNNs) are being employed. Several implementations of drug discovery have currently been analysed and supported the power of the technology in quantitative structure-property relationship (QSPR) or quantitative structure-activity relationship (QSAR). In addition, de novo design promotes the invention of significantly newer drug molecules with regard to desired/optimal qualities. In the current review article, the uses of AI in pharmacy, especially in drug discovery, drug delivery formulation development, polypharmacology and hospital pharmacy are discussed. Key words: Artificial intelligence, Artificial neural network, Drug discovery, Drug delivery research, Hospital pharmacy.

Synthesis of Calcium/Aluminium-Ciprofloxacin-Layered Double Hydroxide for a New Antibacterial Drug Formulation

An antibacterial drug, ciprofloxacin (Cipro) was successfully encapsulated into Ca/Al-layered double hydroxide (CLDH) with molar ratio Ca/Al = 3:1 (R3) by anion exchange method at optimum concentration of 0.2 M Cipro. The successful intercalation was confirmed by patterns analysis of powder X-ray diffraction (PXRD), Fourier transform infrared spectroscopy (FTIR), elemental analysis (CHNS) and accelerated surface area and porosity (ASAP) analysis. Basal spacing of CLDH synthesized in this study is 8.7 Å. Due to the inclusion of Cipro into the layered CLDH, basal spacing expanded to 16.2 Å in Ca/Al-Cipro-LDH (CCLDH) compare to in CLDH. The FTIR spectra of the hybrid nanocomposite show resemblance peaks of the layered double hydroxide (LDH) and Cipro, indicating the inclusion of the drug anion into the LDH interlamellae. The percentage loading of Cipro calculated from the data obtained from CHNS is 75.9% (w/w). This shows that Ca/Al-layered double hydroxide, CLDH has prospective application as the host for ciprofloxacin (1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylic acid), an antibacterial drug for a novel drug delivery formulation.

Lipid-Based Nanocarriers as Topical Drug Delivery Systems for Intraocular Diseases.

Effective drug delivery to intraocular tissues remains a great challenge due to complex anatomical and physiological barriers that selectively limit the entry of drugs into the eye. To overcome these challenges, frequent topical application and regular intravitreal injections are currently used to achieve the desired drug concentrations into the eye. However, the repetitive installation or recurrent injections may result in several side effects. Recent advancements in the field of nanoparticle-based drug delivery have demonstrated promising results for topical ophthalmic nanotherapies in the treatment of intraocular diseases. Studies have revealed that nanocarriers enhance the intraocular half-life and bioavailability of several therapies including proteins, peptides and genetic material. Amongst the array of nanoparticles available nowadays, lipid-based nanosystems have shown an increased efficiency and feasibility in topical formulations, making them an important target for constant and thorough research in both preclinical and clinical practice. In this review, we will cover the promising lipid-based nanocarriers used in topical ophthalmic formulations for intraocular drug delivery.

Thermosensitive Chitosan-β-Glycerophosphate Hydrogels as Targeted Drug Delivery Systems: An Overview on Preparation and Their Applications.

Today, with the advances in technology and science, more advanced drug delivery formulations are required. One of these new systems is an intelligent hydrogel. These systems are affected by the environment or conditions that become a gel, stay in the circumstance for a certain period, and slowly release the drug. As an advantage, only a lower dose of the drug is required, and it provides less toxicity and minor damage to other tissues. Hydrogels are of different types, including temperature-sensitive, pH-sensitive, ion change-sensitive, and magnetic field-sensitive. In this study, we investigated a kind of temperature-sensitive smart hydrogel, which has a liquid form at room temperature and becomes gel with increasing temperature. Chitosan-β-glycerophosphate hydrogels have been researched and used in many studies. This study investigates the various factors that influence the gelation mechanism, such as gel formation rates, temperature, pH, time, and gel specificity. Hydrogels are used in many drug delivery systems and diseases, including nasal drug delivery, vaginal drug delivery, wound healing, peritoneal adhesion, ophthalmic drug delivery, tissue engineering, and peptide and protein delivery. Overall, the chitosan-β-glycerophosphate hydrogel is a suitable drug carrier for a wide range of drugs. It shows little toxicity to the body, is biodegradable, and is compatible with other organs. This system can be used in different conditions and different medication ways, such as oral, nasal, and injection.

Sodium alginate and pectin estimation in raft forming pharmaceuticals by high performance liquid chromatography method

AbstractThe high performance liquid chromatographic (HPLC) method was developed for the combined estimation of sodium alginate and pectin in raft forming pharmaceuticals on C18 column ZORBAX ODS (1.5 cm × 4.6 mm, 5 μm) with UV detection at 378 nm. The assay condition comprised of phosphate buffer pH 7.4 and methanol 60:40% v/v at a flow rate of 1.25 mL/min. The separation of sodium alginate and pectin with good resolution and a retention time less than 8 min was attained. The method was linear over a range of 200–800 μg/mL of sodium alginate and pectin. The regression values obtained from linearity curve of sodium alginate and pectin were 0.9993 and 0.9991, respectively. The retention time of sodium alginate and pectin was 3.931 and 7.470 min, respectively. The percent recovery of sodium alginate and pectin ranged from 94.2–98.5% and 92.1–98.4% respectively. The limit of detection (LOD) and limit of quantification (LOQ) of sodium alginate were found to be 2.443 and 3.129 μg/mL and the LOD and LOQ of pectin were 3.126 and 3.785 μg/mL, respectively. The resolution of sodium alginate and pectin was found in the range of 1.03–1.89 and 1.10–1.91, respectively. This method has been successfully applied to analyze the concentrations of sodium alginate and pectin in raft forming drug delivery systems.

Cross-linked valerolactone copolymer implants with tailorable biodegradation, loading and in vitro release of paclitaxel

Implantable drug delivery systems, formed from degradable and non-degradable polymers, can offer several advantages over traditional dosage forms for sustained drug delivery. The majority of degradable implant systems developed to date are composed of poly(lactide-co-glycolide) (PLGA). However, PLGA-based systems are not suitable for the delivery of all drugs. Each drug is unique in terms of physico-chemical properties, and polymer-drug compatibility plays a significant role in determining a drug formulation's performance. In this study, two novel cross-linkable δ-valerolactone-based copolymers were synthesized and used to prepare cross-linked disc-shaped implants. The manipulation of the composition of the discs and conditions used during drug loading were found to influence various aspects of the delivery system performance including the degree of swelling, degradation, drug-loading and in vitro release. The polymeric discs resulted in no adverse effects following subcutaneous implantation in naïve rats. These studies support further development of cross-linkable valerolactone matrices as implantable formulations for sustained drug delivery.

Preformulation and characterization of raloxifene-loaded lipid nanoparticles for transdermal administration.

Transdermal administration of raloxifene hydrochloride (RLX)-loaded nanostructured lipid carriers (NLCs) has been proposed to circumvent its low oral bioavailability (2%). Preformulation studies were carried out to evaluate drug-excipient compatibility of various adjuvants commonly used for NLC preparation (waxes, cholesterol, compritol, gelucire, span 60, span 80, span 85, tween 80, poloxamer 188, oleic acid, caprylic/capric triglyceride, and castor oil). It was used differential scanning calorimetry (DSC), isothermal stress testing (IST), and solubility studies. The most promising excipients were chosen for NLC obtention, and full characterization was done, including in vitro skin permeation. DSC curves suggested drug-excipient interaction among some compounds, and the IST study showed incompatibility of RLX with waxes, compritol, cholesterol, span 60, and poloxamer 188. Solubility studies helped select gelucire, caprylic/capric triglyceride, span 80, and tween 80 for NLC production. Twelve NLCs were obtained (NLC1 to NLC12), but NLC7 and NLC8 were the most promising ones. In vitro release studies demonstrated that NLC7 and NLC8 were able to control RLX release (14.74 and 9.07% at 24h, respectively) compared with the unloaded drug (> 90% at 24h). Unloaded RLX did not permeate the diffusion cells' receptor medium and showed higher drug skin retention (11-fold) than RLX-loaded NLC. NLC reduced RLX skin retention, favoring drug permeation to deeper skin layers. NLC7 increased drug flux is 2.4-fold. NLC7 is a promising formulation for RLX transdermal drug delivery.

The APEX1/miRNA-27a-5p axis plays key roles in progression, metastasis and targeted chemotherapy of gastric cancer

Gastric cancer (GC) presents a challenge for conventional therapeutics due to low targeting specificity and subsequent elicitation of multiple drug resistance (MDR). As an essential enzyme for DNA repair, apurinic/apyrimidinic endodeoxyribonuclease 1 (APEX1) exhibits multiple functions to affect cancer malignancy and is excessively expressed in GC. However, the roles APEX1 and its inhibitor miR-27a-5p play in modulating GC progression and MDR development remains unclear. Here, we verified APEX1 as a target of miR-27a-5p and subsequently established the APEX1-deleted SGC-7901 cell line by CRISPR/Cas9 editing. The roles of the APEX1/miR-27a-5p axis in GC progression, metastasis and doxorubicin (DOX) resistance were explored by the targeted chemotherapy facilitated by a GC-specific peptide (GP5) functionalized liposomal drug delivery formulation (GP5/Lipo/DOX/miR-27a-5p). The results showed that APEX1 deletion distinctly attenuated cell growth and metastatic properties in GC, and also sensitized GC cells to DOX. Notably, miR-27a-5p was validated as a suppressor of APEX1-dependent GC development and DOX resistance by a RAS/MEK/FOS and PTEN/AKT/SMAD2 pathway-dependent manner. The altered expression of epithelial-mesenchymal transition (EMT) signatures and signal pathway proteins in the APEX1-deleted cells implied that APEX1 potentially enhances DOX resistance of GC cells by altering the regulation of MAPK and AKT pathways, leading to compromised efficacy of chemotherapy or by initiating additional DNA damage response pathways. Taken together, these findings revealed that as a novel therapeutic target, APEX1/miR-27a-5p axis plays essential roles in modulating the GC development and MDR, and the GC targeted drug delivery formulation presents a strategic reference for the future designation of chemotherapeutics study.

Structure, thermotropic phase behavior and membrane interaction of N-acyl-β-alaninols. Homologs of stress-combating N-acylethanolamines

β-Alaninol and its derivatives were reported to exhibit interesting biological and pharmacological activities and showed potential application in formulating drug delivery vehicles. In the present study, we report the synthesis and characterization of N-acyl-β-alaninols (NABAOHs) bearing saturated acyl chains (n = 8–20) with respect to thermotropic phase behavior, supramolecular organization and interaction with diacylphosphatidylcholine, a major membrane lipid. Results obtained from DSC and powder XRD studies revealed that the transition temperatures (Tt), transition enthalpies (ΔHt), transition entropies (ΔSt) and d-spacings of NABAOHs show odd-even alteration. A linear dependence was observed in the values of ΔHt and ΔSt on the acyl chain length, independently for even and odd acyl chains in both dry and hydrated states; further, the even chainlength molecules exhibited higher values than the odd chainlength series. The crystals structures of N-lauroyl-β-alaninol and N-palmitoyl-β-alaninol, solved in monoclinic system in the P21/c space group, show that the NABAOHs adopt a tilted bilayer structure. A number of NH⋯O, O—H⋯O, and C—H⋯O hydrogen bonds between the hydroxyl and amide moieties of the head groups of NABAOH molecules belonging to adjacent and opposite layers stabilize the overall supramolecular organization of the self-assembled bilayer system. DSC studies on the interaction of N-myristoyl-β-alaninol (NMBAOH) with dimyristoylphosphatidylcholine (DMPC) indicate that these two lipids mix well up to 45 mol% NMBAOH, whereas phase separation was observed at higher contents of NMBAOH. Transmission electron microscopic studies reveal that mixtures containing 20−50 mol% NMBAOH form stable ULVs of 90−150 nm diameter, suitable for use in drug delivery applications.

“Mucus-on-Chip”: A new tool to study the dynamic penetration of nanoparticulate drug carriers into mucus

The mucus covering of epithelial tissues presents one significant biological barrier to the uptake and absorption of particulate carriers. Improved understanding of the mechanisms mediating the transport of nanoparticles across such mucus layers would accelerate their development as optimised mucosal drug delivery formulations (e.g. via oral and rectal routes). Herein, an in vitro mucus model (“Mucus-on-Chip”) was developed to enable the interaction and transport of functionalised nanoparticles and reconstituted mucus to be quantitatively investigated in real-time. We verified that the diffusion of nanoparticles into mucus is highly dependent on their biointerfacial properties. Muco-inert modification (PEGylation) significantly enhanced the mucopenetration of 50 nm and 200 nm nanoparticles, whereas limited mucopenetration was observed for pectin coated mucoadhesive nanoparticles. Furthermore, this model can be easily adapted to mimic specific physiological mucus environments. Mucus pre-treated with a mucolytic agent displayed reduced barrier function and therefore significantly accelerated mucopenetration of nanoparticles, which was independent of their size and biointerfacial properties. This new “Mucus-on-Chip” methodology provides detailed insight into the dynamics of nanoparticle-mucus interaction, which can be applied to refine the design of particulate formulations for more efficient mucosal drug delivery.

A Brief Review on Nanoparticles: Type of Platforms, Biological synthesis & Evaluation

Nanoparticles refers to as particulate dispersions or solid particles with a size in the range of 10-1000nm. The nanoparticles have been used to alter the physical approach and improve the pharmacokinetic and pharmacodynamic properties of many type of drug molecules. They have significant advantages in conventional drug delivery in form of high specificity, high stability, high drug carrying capacity, control release ability, possibility occurs to different rout of administration and having a capability to deliver hydrophobic and hydrophilic drug molecules. This review focuses on type, preparation and evaluation of nanoparticles.

Drug delivery formulation impacts cyclosporine efficacy in a humanised mouse model of acute graft versus host disease

Acute graft versus host disease (aGvHD) is an allogeneic T cell mediated disease which manifests as a severe inflammatory disease affecting multiple organs including the liver, skin, lungs and gastrointestinal tract. Existing prophylactic and therapeutic approaches in aGvHD include the use of cyclosporine A (CyA), however the currently approved CyA formulations which were designed to optimise systemic CyA bioavailability can have a number of side effects including nephrotoxicity as well as the potential to attenuate the beneficial Graft-versus-Leukemia (GvL) effect. An added complication with CyA is that it has a narrow therapeutic window, and following oral administration is absorbed only from the small intestine, with variable cytochrome P450 metabolism contributing to intra- and inter-patient variability. This study sought to investigate the efficacy of a novel CyA oral formulation enabled by the integrated SmPill® oral drug delivery platform in a humanised mouse model of aGvHD. The study compared the approved optimised CyA (Neoral®) with SmPill®-enabled CyA and a systemic intravenous CyA formulation. Our findings clearly demonstrate superior efficacy of the novel SmPill® CyA in prolonging survival in a clinically relevant humanised aGvHD model. SmPill® CyA significantly reduced pathological score in the small intestine, colon, liver and lung of aGvHD mice. In addition, SmPill® CyA significantly reduced the levels of pro-inflammatory cytokines in all the GvHD target tissues examined. Notably, SmPill® CyA was significantly more potent in reducing GvHD associated pathology and inflammatory cytokine production compared to the optimised approved oral CyA formulation, Neoral®.

Recent trends of self-emulsifying drug delivery system for enhancing the oral bioavailability of poorly water-soluble drugs

The oral route is the most popular route for the clinical administration of drugs to treat various diseases. Before a drug is absorbed into the blood circulation, it must undergo dissolution and permeation. However, most drugs exhibit poor aqueous solubility, and their limited absorption leads to low oral bioavailability. The solubility of hydrophobic drugs can be improved by various ways, such as solid dispersion, salt formation, pH modification, and self-emulsifying drug delivery system (SEDDS) use. Among them, the SEDDS has garnered attention during recent years as it improves oral bioavailability, reduces drug dose, and increases drug protection from unsuitable environment in the gastrointestinal tract. SEDDS comprises lipid-based formulations. It can solve the problems related to the dissolution and bioavailability of the Biopharmaceutics Classification System Class II and IV drugs. Depending on the preparation procedure, drug-loaded SEDDS can be divided into micro- (SMEDDS) and nano- (SNEDDS) formulations. In this review, we summarize the classification system of lipid formulations, the mechanism underlying improved oral drug absorption by SEDDS, and recent advances in the SEDDS. The SEDDS is a potential formulation for drug delivery. Owing to its small particle size, large surface area, high encapsulation efficiency, and high drug loading, the SEDDS can improve the rate and extent of oral absorption by maximizing drug solubility in the intestinal absorption site. Moreover, because of the lipid-based formulation of SEDDS, it can stimulate and enhance lymphatic transport of drugs to avoid hepatic first-pass metabolism, and thus improve their bioavailability.

Hydroxypropyl methylcellulose: Physicochemical properties and ocular drug delivery formulations

Hydroxypropyl methylcellulose (HPMC) is a cellulose ether widely used in drug formulations due to its biocompatibility, uncharged nature, solubility in water and thermoplastic behavior. Particularly for ocular and ophthalmic formulations, HPMC is applied as viscosity enhancer agent in eye drops, gelling agent in injections, and polymeric matrix in films, filaments and inserts. The different therapeutic approaches are necessary due to the complex anatomic structure of the eye. The natural ocular barriers and the low drug permeation into the circulatory system make the drug administration challenging. This review presents the eye anatomy and the usual local routes of drugs administration, which are facilitated by the physicochemical properties of HPMC. The relationship between chemical structure and physicochemical properties of HPMC is displayed. The different types of formulations (local application) including HPMC for ocular drug delivery are discussed with basis on recent literature reports and patents.

Hyaluronidase Inhibitor-Incorporated Cross-Linked Hyaluronic Acid Hydrogels for Subcutaneous Injection.

Hyaluronidase (HAase) inhibitor-incorporated hyaluronic acid (HA) hydrogel cross-linked with 1,4-butanediol diglycidyl ether (BDDE) was designed to reduce the toxicity risk induced by BDDE and its biodegradation rate in subcutaneous tissue. The formulation composition of hydrogel and its preparation method were optimized to have a high swelling ratio and drug content. Quercetin (QCT) and quetiapine (QTP), as an HAase inhibitor and model drug, respectively, were incorporated into the cross-linked hydrogel using the antisolvent precipitation method for extending their release after subcutaneous injection. The cross-linked HA (cHA)-based hydrogels displayed appropriate viscoelasticity and injectability for subcutaneous injection. The incorporation of QCT (as an HAase inhibitor) in the cHA hydrogel formulation resulted in slower in vitro and in vivo degradation profiles compared to the hydrogel without QCT. Single dosing of optimized hydrogel injected via a subcutaneous route in rats did not induce any acute toxicities in the blood chemistry and histological staining studies. In the pharmacokinetic study of rats following subcutaneous injection, the cHA hydrogel with QCT exhibited a lower maximum QTP concentration and longer half-life and mean residence time values compared to the hydrogel without QCT. All of these results support the designed HAase inhibitor-incorporated cHA hydrogel being a biocompatible subcutaneous injection formulation for sustained drug delivery.

A Review on Exploring Better Safety Prospects in Managing Cancer using Liposomal Combinations of Food Bioactive Compounds and Anticancer Drugs: Combisomes.

Nowadays, cancer is one of the deadliest diseases affecting an annually enormous number of people. Around 9.6 million people had died from different cancer types in 2018. Chemotherapy is considered to be a mainline treatment, and systemic administration of a single anticancer agent is also considered a vital clinical debacle of chemotherapy in cancer management. The formulators have been focusing currently onto procuring maximum benefit with the lowest aftereffects and maximum safety and efficacy for the patients undergoing chemotherapy. This review offers a perspective on the future developments of encapsulating food bioactive compounds with anticancer agents in a multifunctional single nanoliposomal delivery system. In the last decade, the paradigm shift was seen in formulating drug delivery systems for cancer treatment. Currently, food bioactive compounds are being taken as a hot subject by researchers, especially for the treatment of cancer owing to both preventative and curative quality. This review collects the utilization of liposomes in the delivery of anticancer drugs by encapsulating with food bioactive compounds by the oral administration. The authors coined the name of this combination is "Combisomes" as a fourth generation liposomes. Authors opine that "Combisomes" can tackle cancer minimizing side effects encountered from the usual anticancer agents. "Combisomes" will purvey a safe platform for the delivery of food bioactive compounds and anticancer agents for managing cancer with better safety prospects.

Review on Conventional and Novel Topical Ocular Drug Delivery System

Ocular drug delivery is a very challenging area for ophthalmologists and drug delivery scientists due to the structural and barrier complexity of the eye. Barriers such as different layers of cornea, sclera, conjunctival blood flow, and tear dilution limit the efficacy of drug delivery to the anterior part of the eye in addition to more barriers present to the posterior part. Due to these, scientists have designed and studied various delivery systems to increase drug delivery and treatment efficacy to the eye. Among conventional ocular drug delivery systems, ophthalmic solution or eye drop is widely used and preferred by consumers. Conventional dosage forms available in the market are emulsion, suspension, ointment and polymeric gels. Several ocular formulations such as nano-formulations, liposomes, ocular inserts, and ocular mini-tablets are also being widely studied as future treatments to improve ocular drug delivery and as an alternative to conventional drug delivery. This review intends to summarise several conventional and novel topical formulations for ocular drug delivery.

Bio-inspired multifunctional collagen/electrospun bioactive glass membranes for bone tissue engineering applications

Treatment of bone disease and disorders is often challenging due to its complex structure. Each year millions of people needs bone substitution materials with quick recovery from diseases conditions. Synthetic bone substitutes mimicking structural, chemical and biological properties of bone matrix structure will be very obliging and of copious need. In this work, we reported on the fabrication of bioinspired, biomimetic, multifunctional bone-like three-dimensional (3D) membranes made up of inorganic bioactive glass fibers matrixed organic collagen structure. The 3D structure is arranged as a stacked-layer similar to the order of apatite and neotissue formation. Comparative studies on collagen, collagen with hollow and solid bioactive glass fibers evidenced that, collagen/hollow bioactive glass is mechanically robust, has optimal hydrophilicity, simultaneously promotes bioactivity and in situ forming drug delivery. The 3D membrane displays outstanding mechanical properties apropos to the bioactive glass fibers arrangement, with its Youngs modulus approaching the modulus of cortical bone. The in vitro cell culture studies with fibroblast cells (3T3) on the membranes display enhanced cell adhesion and proliferation with the cell alignment similar to anisotropic cell alignment found in the native bone extracellular matrix. The membranes also support 3D cell culturing and exhibits cell proliferation on the membrane surface, which extends the possibility of its bone tissue engineering application. The alkaline phosphatase assessment and alizarin red staining of osteoblast cells (MG63) depicted an enhanced osteogenic activity of the membranes. Notable Runx2, Col-Type-1 mRNA, osteocalcin, and osteonectin levels were found to be significantly increased in cells grown on the collagen/hollow bioactive glass membrane. This membrane also promotes vascularization in the chick chorioallantoic membrane model. The results altogether evidence this multifunctional 3D membrane could potentially be utilized for treatment of bone defects.

An Electrochemical Strategy for the Simultaneous Detection of Doxorubicin and Simvastatin for Their Potential Use in the Treatment of Cancer.

The aim of this study was to develop a disposable, simple, fast, and sensitive sensor for the simultaneous electrochemical detection of doxorubicin (DOX) and simvastatin (SMV), which could be used in preclinical studies for the development of new pharmaceutical formulations for drug delivery. Firstly, the electrochemical behavior of each molecule was analyzed regarding the influence of electrode material, electrolyte solution, and scan rate. After this, the proper electrode material, electrolyte solution, and scan rate for both active substances were chosen, and a linear sweep voltammetry procedure was optimized for simultaneous detection. Two chronoamperometry procedures were tested, one for the detection of DOX in the presence of SMV, and the other one for the detection of DOX and SMV together. Finally, calibration curves for DOX and SMV in the presence of each other were obtained using both electrochemical methods and the results were compared. The use of amperometry allowed for a better limit of detection (DOX: 0.1 μg/mL; SMV: 0.7 μg/mL) than the one obtained in voltammetry (1.5 μg/mL for both drugs). The limits of quantification using amperometry were 0.5 μg/mL for DOX (dynamic range: 0.5–65 μg/mL) and 2 μg/mL for SMV (dynamic range: 2–65 μg/mL), while using voltammetry 1 μg/mL was obtained for DOX (dynamic range: 1–100 μg/mL) and 5 μg/mL for SMV (dynamic range: 5–100 μg/mL). This detection strategy represents a promising tool for the analysis of new pharmaceutical formulations for targeted drug delivery containing both drugs, whose association was proven to bring benefits in the treatment of cancer.