Due to the inability to curb the excessive increase in the prevalence of obesity and overweight, it is necessary to comprehend in more detail the factors involved in the pathophysiology and to appreciate more clearly the biochemical and molecular mechanisms of obesity. Thus, understanding the biological regulation of adipose tissue is of fundamental relevance. Connexin, a protein that forms intercellular membrane channels of gap junctions and unopposed hemichannels, plays a key role in adipogenesis and in the maintenance of adipose tissue homeostasis. The expression and function of Connexin 43 (Cx43) during the different stages of the adipogenesis are differentially regulated. Moreover, it has been shown that cell–cell communication decreases dramatically upon differentiation into adipocytes. Furthermore, inhibition of Cx43 degradation or constitutive overexpression of Cx43 blocks adipocyte differentiation. In the first events of adipogenesis, the connexin is highly phosphorylated, which is likely associated with enhanced Gap Junction (GJ) communication. In an intermediate state of adipocyte differentiation, Cx43 phosphorylation decreases, as it is displaced from the membrane and degraded through the proteasome; thus, Cx43 total protein is reduced. Cx is involved in cardiac disease as well as in obesity-related cardiovascular diseases. Different studies suggest that obesity together with a high-fat diet are related to the production of remodeling factors associated with expression and distribution of Cx43 in the atrium.

The biopharmaceutical classification system groups low-solubility drugs into two groups: II and IV, with high and low permeability, respectively. Most of the new drugs developed for common pathologies present solubility issues. This is the case of lurasidone hydrochloride—a drug used for the treatment of schizophrenia and bipolar depression. Likewise, the stability problems of some drugs limit the possibility of preparing them in liquid pharmaceutical forms where hydrolysis and oxidation reactions can be favored. Lurasidone hydrochloride presents the isoindole-1,3-dione ring, which is highly susceptible to alkaline hydrolysis, and the benzisothiazole ring, which is susceptible to a lesser extent to oxidation. Herein, we propose to study the increase in the solubility and stability of lurasidone hydrochloride by the formation of higher-order inclusion complexes with hydroxypropyl-β-cyclodextrin. Several stoichiometric relationships were studied at between 0.5 and 3 hydroxypropyl-β-cyclodextrin molecules per drug molecule. The obtained products were characterized, and their solubility and stability were assessed. According to the obtained results, the formation of inclusion complexes dramatically increased the solubility of the drug, and this increased with the increase in the inclusion ratio. This was associated with the loss of crystalline state of the drug, which was in an amorphous state according to infrared spectroscopy, calorimetry, and X-ray analysis. This was also correlated with the stabilization of lurasidone by the cyclodextrin inhibiting its recrystallization. Phase solubility,¹H-NMR, and docking computational characterization suggested that the main stoichiometric ratio was 1:1; however, we cannot rule out a 1:2 ratio, where a second cyclodextrin molecule could bind through the isoindole-1,3-dione ring, improving its stability as well. Finally, we can conclude that the formation of higher-order inclusion complexes of lurasidone with hydroxypropyl-β-cyclodextrin is a successful strategy to increase the solubility and stability of the drug.

Background/Objectives: Amlodipine is an antihypertensive agent characterized by low aqueous solubility and variable oral bioavailability. This study aimed to formulate and characterize amlodipine–alginate nanoplexes and to incorporate the optimized system into an oral film dosage form. Methods: Nanoplexes were prepared via ionic complexation employing alginates (ALG) with diverse physicochemical properties, including low (LV) and medium (MV)-viscosity grades, as well as alginates with varying M/G ratios. The nanoplexes were thoroughly characterized employing a comprehensive set of analytical techniques. In addition, intermolecular interactions were examined using computational simulation studies. Results: The nanoplexes demonstrated high encapsulation efficiencies (>80%), with MV alginate yielding particles with greater drug loading but larger mean diameters compared with that prepared using LV alginate. Computational simulation studies revealed favorable interaction energies between the drug and the polyelectrolyte, particularly within microenvironments enriched in guluronic acid–rich repeat regions. These interactions were corroborated by infrared spectroscopy, while differential scanning calorimetry and X-ray diffraction analysis confirmed the amorphous solid state of amlodipine within the nanoplexes. Dissolution studies demonstrated an inverse relationship between alginate viscosity and drug release rate, with formulations based on LV alginate exhibiting rapid drug release. The final hydroxypropylmethylcellulose film incorporating ALG-MV nanoplexes exhibited adequate mechanical integrity and achieved approximately 95% drug release within 30 min. Conclusions: The developed film presenting a viable approach to enhance the delivery of amlodipine. Overall, this approach constitutes a significant advancement in the delivery of poorly soluble drugs through the integration of nanostructured systems with flexible oral film platforms.