Cyclodextrin Complex Formation with Water-Soluble Drugs: Conclusions from Isothermal Titration Calorimetry and Molecular Modeling.

Cyclodextrin (CD) complexes are frequently used for enhancing the solubility or absorption of poorly water-soluble drugs. On the contrary, little is known about their complex formation with water-soluble drugs. Here, we have studied the interaction between 2-hydroxypropyl ß-CD (HPßCD) and three water-soluble drugs, namely naloxone (NX), oxycodone (OC), and tramadol (TR), by isothermal titration calorimetry (ITC) combined with molecular modeling in view of the potential impact on drug release. The results showed that the complex formation of HPßCD with all three drugs occurs spontaneously. The complexes formed with NX and OC were found to be 2NX:1HPßCD and 3OC:2HPßCD, respectively. TR was found to form 2 complexes with HPßCD; of 1:2 and 1:1 complexation ratios. The binding of HPßCD to NX was greater than to OC due to the higher hydrophobicity of the structure of the former. Moreover, the binding affinity of HPßCD to TR was higher than to OC, which indicated the effect of the higher flexibility of the guest in increasing the binding affinity. In vitro drug release experiments from the various complexes revealed a significant impact of the stoichiometry of the complex on the release profiles. Accordingly, the co-administration of cyclodextrins with water-soluble drugs should be closely monitored, as it may result in unintentional complex formation that can potentially impact the drugs' gastrointestinal absorption.

Drug delivery to the inflamed intestinal mucosa - targeting technologies and human cell culture models for better therapies of IBD.

Current treatment strategies for inflammatory bowel disease (IBD) seek to alleviate the undesirable symptoms of the disorder. Despite the higher specificity of newer generation therapeutics, e.g. monoclonal antibodies, adverse effects still arise from their interference with non-specific systemic immune cascades. To circumvent such undesirable effects, both conventional and newer therapeutic options can benefit from various targeting strategies. Of course, both the development and the assessment of the efficiency of such targeted delivery systems necessitate the use of suitable in vivo and in vitro models representing relevant pathophysiological manifestations of the disorder. Accordingly, the current review seeks to provide a comprehensive discussion of the available preclinical models with emphasis on human in vitro models of IBD, along with their potentials and limitations. This is followed by an elaboration on the advancements in the field of biology- and nanotechnology-based targeted drug delivery systems and the potential rooms for improvement to facilitate their clinical translation.

Nanoparticles Based on Linear and Star-Shaped Poly(Ethylene Glycol)-Poly(ε-Caprolactone) Copolymers for the Delivery of Antitubulin Drug.

PURPOSE: Biodegradable polymeric nanoparticles of different architectures based on polyethylene glycol-co-poly(ε-caprolactone) block copolymers have been loaded with noscapine (NOS) to study their effect on its anticancer activity. It was intended to use solubility of NOS in an acidic environment and ability of the nanoparticles to passively target drugs into cancer tissue to modify the NOS pharmacokinetic properties and reduce the requirement for frequent injections. METHODS: Linear and star-shaped copolymers were synthetized and used to formulate NOS loaded nanoparticles. Cytotoxicity was performed using a sulforhodamine B method on MCF-7 cells, while biocompatibility was determined on rats followed by hematological and histopathological investigations. RESULTS: Formulae with the smallest particle sizes and adequate entrapment efficiency revealed that NOS loaded nanoparticles showed higher extent of release at pH 4.5. Colloidal stability suggested that nanoparticles would be stable in blood when injected into the systemic circulation. Loaded nanoparticles had IC50 values lower than free drug. Hematological and histopathological studies showed no difference between treated and control groups. Pharmacokinetic analysis revealed that formulation P1 had a prolonged half-life and better bioavailability compared to drug solution. CONCLUSIONS: Formulation of NOS into biodegradable polymeric nanoparticles has increased its efficacy and residence on cancer cells while passively avoiding normal body tissues. Graphical Abstract ᅟ.

Determination of factors controlling the particle size and entrapment efficiency of noscapine in PEG/PLA nanoparticles using artificial neural networks.

In this study, di- and triblock copolymers based on polyethylene glycol and polylactide were synthesized by ring-opening polymerization and characterized by proton nuclear magnetic resonance and gel permeation chromatography. Nanoparticles containing noscapine were prepared from these biodegradable and biocompatible copolymers using the nanoprecipitation method. The prepared nanoparticles were characterized for size and drug entrapment efficiency, and their morphology and size were checked by transmission electron microscopy imaging. Artificial neural networks were constructed and tested for their ability to predict particle size and entrapment efficiency of noscapine within the formed nanoparticles using different factors utilized in the preparation step, namely polymer molecular weight, ratio of polymer to drug, and number of blocks that make up the polymer. Using these networks, it was found that the polymer molecular weight has the greatest effect on particle size. On the other hand, polymer to drug ratio was found to be the most influential factor on drug entrapment efficiency. This study demonstrated the ability of artificial neural networks to predict not only the particle size of the formed nanoparticles but also the drug entrapment efficiency. This may have a great impact on the design of polyethylene glycol and polylactide-based copolymers, and can be used to customize the required target formulations.