Theranostic Effect of Folic Acid Functionalized MIL-100(Fe) for Delivery of Prodigiosin and Simultaneous Tracking-Combating Breast Cancer

The metal organic framework (MOF) member, MIL-100(Fe), is considered as attractive drug nanocarrier that may be due to the great porosity, colloidal stability, and biocompatibility. In the present study, the new electrochemical synthesis procedure was presented for MIL-100(Fe) building block, and secondly, folic acid (FA) was introduced to the structure for assessing its potential targeted ability to be entrapped by folic acid-positive breast cancer cells, MCF-7. Several techniques such as SEM, XRD, and FT-IR were used to characterize synthesized nanostructures. Both MIL-100(Fe) and MIL-100(Fe)/FA nanoparticles were between 50 to 200 nm with a slightly positive net charge with an area of 1350 and 831.84 m2/g, respectively. The prodigiosin (PG) is selected as a model drug for MIL-100(Fe) and MIL-100(Fe)/FA-targeted delivery owing to its natural fluorescence and cancer cell selectiveness. The loading capacity of both nanocarrier was around 40% with 93-97% loading efficacy. Moreover, the pH-sensitive prodigiosin release rate of MIL-100(Fe)@PG and MIL-100(Fe)/FA@PG showed that 69 to 73% of the drug was released after 24 hours in an acidic environment with around 20% unwanted leakage. The anticancer potential MIL-100(Fe)/FA cells showed the improvement of selective index (SI) from 3.21 to 12.48 which means that folic acid acts as an effective ligand. The study of cells treated with fluorescence microscopy and flow cytometry analysis reveals the dependence of the receptor on the nanoparticle through endocytosis. Considering the effects of nanoparticles on healthy cells, MIL-100(Fe) and MIL-100(Fe)/FA nanoparticles can be introduced as targeted drug delivery systems for smart targeting breast cancer cells with minimal side effects.

Functionalizing Fibrin Hydrogels with Thermally Responsive Oligonucleotide Tethers for On-Demand Delivery

There are a limited number of stimuli-responsive biomaterials that are capable of delivering customizable dosages of a therapeutic at a specific location and time. This is especially true in tissue engineering and regenerative medicine applications, where it may be desirable for the stimuli-responsive biomaterial to also serve as a scaffolding material. Therefore, the purpose of this study was to engineer a traditionally non-stimuli responsive scaffold biomaterial to be thermally responsive so it could be used for on-demand drug delivery applications. Fibrin hydrogels are frequently used for tissue engineering and regenerative medicine applications, and they were functionalized with thermally labile oligonucleotide tethers using peptides from substrates for factor XIII (FXIII). The alpha 2-plasmin inhibitor peptide had the greatest incorporation efficiency out of the FXIII substrate peptides studied, and conjugates of the peptide and oligonucleotide tethers were successfully incorporated into fibrin hydrogels via enzymatic activity. Single-strand complement oligo with either a fluorophore model drug or platelet-derived growth factor-BB (PDGF-BB) could be released on demand via temperature increases. These results demonstrate a strategy that can be used to functionalize traditionally non-stimuli responsive biomaterials suitable for on-demand drug delivery systems (DDS).

Rheological and textural analysis as tools for investigation of drug-polymer and polymer–polymer interactions on the example of low-acyl gellan gum and mesalazine

Purpose. In the performed study, the rheological and textural parameters of gellan-based hydrogels were investigated and their dependence on three factors was taken into consideration: ( i) The presence of the model drug, ( ii) The presence and type of the ionic crosslinking agent, and ( iii) the composition of the polymer network. The objective was to compare two analytical methods, regarded as complementary, and define to what extent the obtained results correlate with each other. Methods. The hydrogels contained low-acyl gellan gum or its mixtures with hydroxyethyl cellulose or κ-carrageenan. CaCl2 and MgCl2 were used as gelling agents. Mesalazine was used as a model drug. The rheological analysis included oscillatory stress and frequency sweeping. The texture profile analysis was performed to calculate texture parameters. Results. Placebo gels without the addition of gelling agents had the weakest structure. The drug had the strongest ability to increase the stiffness of the polymer network. The weakest structure revealed the placebo samples without the addition of gelling agents. Texture analysis revealed no significant influence of the drug on the strength of the gels, while rheological measurements indicated clear differences. Conclusions. It can be concluded that in the case of some parameters methods correlate, that is, the effect related to gelling ions. However, the rheological analysis seems to be more precise and sensitive to some changes in the mechanical properties of the gels.

Mucilage of Coccinia grandis as an Efficient Natural Polymer-Based Pharmaceutical Excipient

Natural eco-friendly materials are recently employed in products to replace synthetic materials due to their superior benefits in preserving the environment. The herb Coccinia grandis is widely distributed in continents like Asia and Africa and used traditionally to treat fever, leprosy, asthma, jaundice, and bronchitis. Mucilage of Coccinia grandis was accordingly extracted, isolated by a maceration technique, and precipitated. The mucilage was evaluated for its physicochemical, binding, and disintegrant properties in tablets using paracetamol as a model drug. The crucial physicochemical properties such as flow properties, solubility, swelling index, loss on drying, viscosity, pH, microbial load, cytotoxicity was evaluated and the compatibility was analyzed using sophisticated instrumental methods (TGA, DTA, DSC, and FTIR). The binding properties of the mucilage was used at three different concentrations and compared with starch and PVP as examples of standard binders. The disintegrant properties of mucilage were used at two different concentrations and compared with standard disintegrants MCCP, SSG, and CCS. The tablets were punched and evaluated for their hardness, friability, assay, disintegration time, in vitro dissolution profiles. In vitro cytotoxicity studies of the mucilage were performed in a human embryonic kidney (HEK) cell line. The outcome of the study indicated that the mucilage had good performance compared with starch and PVP. Further, the mucilage acts as a better disintegrant than MCCP, SSG and CCS for paracetamol tablets. Use of a concentration of 3% or less demonstrated the ability of the mucilage to act as a super disintegrating agent and showed faster disintegration and dissolution, which makes it as an attractive, promising disintegrant in formulating solid dosage forms to improve the therapeutic efficacy and patient compliance. Moreover, the in vitro cytotoxicity evaluation results demonstrated that the mucilage is non-cytotoxic to human cells and is safe.

Preparation, Characteristics, and Controlled Release Efficiency of the Novel PCL-PEG/EM Rod Micelles

In order to achieve sustained and controlled release of the hydrophobic cargoes, improve the bioavailability, and reduce the side effects of antibiotics, the model drug erythromycin (EM) was used to prepare polycaprolactone-polyethylene glycol (PCL-PEG)/EM micelles. PCL-PEG, a biocompatible and biodegradable amphiphilic polymer, was used as carrier material of micelles to optimize the formulation and preparation process by orthogonal design. The morphology, stability, drug loading, and encapsulation efficiency and the in vitro release behavior of the micelles were investigated. In addition, activity assays of anti-Staphylococcus aureus were performed. The results indicated that PCL-PEG/EM were rod-like micelles with an average particle size of 220 ± 2.6 nm and a zeta potential of +19 mV. The average drug loading and encapsulation efficiency were approximately 6.5% and 97.0%, respectively. The micelles were stable in the serum within three days. At the effective concentration of the drug, the formulation indicated no apparent toxicity to the cells. The micelles were able to rapidly enter Staphylococcus aureus (S. aureus) and to provide sustained release cargoes that effectively inhibited S. aureus proliferation. The present study provided a new platform for the rational and effective use of hydrophobic antibiotics to treat infections.

Effective Management of Rare Lymphangioleiomyomatosis Using Sirolimus: Tablet Matrix with Hibiscus rosa sinensis Leave Mucilage

The authors aimed to extend the discharge of Sirolimus from the tablets with a blend of herbal and synthetic polymers. In this study, Sirolimus was taken as a model drug, Hydroxy Propyl Methyl Cellulose as a synthetic polymer and mucilage from Hibiscus rosa sinensis leaves as a natural polymer. Sirolimus is an orphan drug used to treat Lymphangioleiomyomatosis damage and to suppress body refuse towards the transplanted organs. Sirolimus matrix tablets made with the blend of Hibiscus rosa sinensis leaves mucilage and Hydroxy Propyl Methyl Cellulose. The blend was assessed for flow possessions and the designed tablets were categorized for official and non-official tests including Sirolimus discharge. The Sirolimus matrix tablets possess good Sirolimus content with passible pre and post-formulation parameters. The study concludes that there were no chemical interactions between Sirolimus with polymers used. The study also revealed that Hibiscus rosa sinensis leaves mucilage can be a good polymer in grouping with other polymers for prolonged drug discharge.

Imaging-Guided Delivery of a Hydrophilic Drug to Eukaryotic Cells Based on Its Hydrophobic Ion Pairing with Poly(hexamethylene guanidine) in a Maleated Chitosan Carrier

Imaging-guided delivery is developed for hydrophobic drugs, and to a much lesser extent, hydrophilic ones. In this work we have designed a novel strategy for real-time monitoring of hydrophilic drug delivery. Traditionally, the drug and the dye are covalently attached to a nanocarrier or are electrostatically adsorbed. Recently, we found an efficient way to bind the drug by ion-paring with an appropriate counter-ion to form the aggregate that embeds a hydrophobic dye with a considerable fluorescence enhancement. We synthesized a series of carbocyanine dyes of hydrophobicity sufficient for solubilization in hydrophobic ion pairs, which restores their emission in the near-infrared (NIR) region upon the formation of the ternary aggregates. To avoid using toxic surfactants, we applied an amphiphilic polymer-oligomer poly(hexamethylene guanidine) (PHMG) as a counter-ion. Сeftriaxone was used as a model hydrophilic drug ensuring the highest fluorescent signal. The so-formed drug–counter-ion–dye aggregates were encapsulated into a cross-linked maleated chitosan carrier. Confocal laser scanning microscopy (CLSM) studies have demonstrated internalization of the encapsulated model drug by breast adenocarcinoma cells at 40 min after treatment. These results suggest the potential application of hydrophobic ion pairs containing an NIR dye in imaging-guided delivery of hydrophilic compounds.

Encapsulation of Metronidazole in Biocompatible Macrocycles and Structural Characterization of Its Nano Spray-Dried Nanostructured Composite

Due to the great potential of biocompatible cucurbit[7]uril (CB7) and 4-sulfonatocalix[4]arene (SCX4) macrocycles in drug delivery, the confinement of the pharmaceutically important metronidazole as an ionizable model drug has been systematically studied in these cavitands. Absorption and fluorescence spectroscopic measurements gave 1.9 × 105 M−1 and 1.0 × 104 M−1 as the association constants of the protonated metronidazole inclusion in CB7 and SCX4, whereas the unprotonated guests had values more than one order of magnitude lower, respectively. The preferential binding of the protonated metronidazole resulted in 1.91 pH unit pKa diminution upon encapsulation in CB7, but the complexation with SCX4 led to a pKa decrease of only 0.82 pH unit. The produced protonated metronidazole–SCX4 complex induced nanoparticle formation with protonated chitosan by supramolecular crosslinking of the polysaccharide chains. The properties of the aqueous nanoparticle solutions and the micron-sized solid composite produced therefrom by nano spray drying were unraveled. The results of the present work may find application in the rational design of tailor-made self-assembled drug carrier systems.