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The 18-kDa translocator protein (TSPO) is a potential mitochondrial target for drug delivery to tumors overexpressing TSPO, including brain cancers, and selective TSPO ligands have been successfully used to selectively deliver drugs into the target. Methotrexate (MTX) is an anticancer drug of choice for the treatment of several cancers, but its permeability through the blood brain barrier (BBB) is poor, making it unsuitable for the treatment of brain tumors. Therefore, in this study, MTX was selected to achieve two TSPO ligand-MTX conjugates (TSPO ligand α-MTX and TSPO ligand γ-MTX), potentially useful for the treatment of TSPO-rich cancers, including brain tumors. In this work, we have presented the synthesis, the physicochemical characterizations, as well as the in vitro stabilities of the new TSPO ligand-MTX conjugates. The binding affinity for TSPO and the selectivity versus central-type benzodiazepine receptor (CBR) was also investigated. The cytotoxicity of prepared conjugates was evaluated on MTX-sensitive human and rat glioma cell lines overexpressing TSPO. The estimated coefficients of lipophilicity and the stability studies of the conjugates confirm that the synthesized molecules are stable enough in buffer solution at pH 7.4, as well in physiological medium, and show an increased lipophilicity compared to the MTX, compatible with a likely ability to cross the blood brain barrier. The latter feature of two TSPO ligand-MTX conjugates was also confirmed by in vitro permeability studies conducted on Madin-Darby canine kidney cells transfected with the human MDR1 gene (MDCK-MDR1) monolayers. TSPO ligand-MTX conjugates have shown to possess a high binding affinity for TSPO, with IC50 values ranging from 7.2 to 40.3 nM, and exhibited marked toxicity against glioma cells overexpressing TSPO, in comparison with the parent drug MTX. [ABSTRACT FROM AUTHOR]

Simple Summary: This research suggests a new potential therapeutic approach to pancreatic ductal adenocarcinoma to improve drug effectiveness and overcome drug resistance. A double actively targeted gemcitabine delivery system, consisting of polymeric micelles, was developed by microfluidic technique to ensure a narrow size distribution, a good colloidal stability, and drug-encapsulation efficiency for the selective and controlled release of the loaded drug, in response to the pH variations and uPAR expression in tumors. In vitro studies assessed that the release of the drug in the acidic environment was higher than in the neutral one, and that the pH-responsive and uPAR-targeted polymeric micelles enhanced the antitumor properties of gemcitabine in models resembling the pancreatic tumor microenvironment. Pancreatic ductal adenocarcinoma (PDAC) represents a great challenge to the successful delivery of the anticancer drugs. The intrinsic characteristics of the PDAC microenvironment and drugs resistance make it suitable for therapeutic approaches with stimulus-responsive drug delivery systems (DDSs), such as pH, within the tumor microenvironment (TME). Moreover, the high expression of uPAR in PDAC can be exploited for a drug receptor-mediated active targeting strategy. Here, a pH-responsive and uPAR-targeted Gemcitabine (Gem) DDS, consisting of polymeric micelles (Gem@TpHResMic), was formulated by microfluidic technique to obtain a preparation characterized by a narrow size distribution, good colloidal stability, and high drug-encapsulation efficiency (EE%). The Gem@TpHResMic was able to perform a controlled Gem release in an acidic environment and to selectively target uPAR-expressing tumor cells. The Gem@TpHResMic displayed relevant cellular internalization and greater antitumor properties than free Gem in 2D and 3D models of pancreatic cancer, by generating massive damage to DNA, in terms of H2AX phosphorylation and apoptosis induction. Further investigation into the physiological model of PDAC, obtained by a co-culture of tumor spheroids and cancer-associated fibroblast (CAF), highlighted that the micellar system enhanced the antitumor potential of Gem, and was demonstrated to overcome the TME-dependent drug resistance. In vivo investigation is warranted to consider this new DDS as a new approach to overcome drug resistance in PDAC. [ABSTRACT FROM AUTHOR]

In the last three decades, the development of nanoparticles or nano-formulations as drug delivery systems has emerged as a promising tool to overcome the limitations of conventional delivery, potentially to improve the stability and solubility of active molecules, promote their transport across the biological membranes, and prolong circulation times to increase efficacy of a therapy. Despite several nano-formulations having applications in drug delivery, some issues concerning their safety and toxicity are still debated. This chapter describes the recent available information regarding safety, toxicity, and efficacy of nano-formulations for drug delivery. Several key factors can influence the behavior of nanoparticles in a biological environment, and their evaluation is crucial to design non-toxic and effective nano-formulations. Among them, we have focused our attention on materials and methods for their preparation (including the innovative microfluidic technique), mechanisms of interactions with biological systems, purification of nanoparticles, manufacture impurities, and nano-stability. This chapter places emphasis on the utilization of in silico, in vitro, and in vivo models for the assessment and prediction of toxicity associated with these nano-formulations. Furthermore, the chapter includes specific examples of in vitro and in vivo studies conducted on nanoparticles, illustrating their application in this field., (© 2025. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

The preparation of formulations that are not currently on the market or prepared for customized therapy is possible by pharmaceutical compounding. In this study, incorporation tests of some active pharmaceutical ingredients in five ready-touse lipophilic semisolid vehicles were performed, and the physical stability of the prepared extemporaneous formulations was assessed by performing an accelerated centrifuge test. The results demonstrated that it was possible to formulate physically stable topical medications without using special equipment or instruments, ensuring a fast, efficient, and repeatable preparation process. The objective of this work was to provide to compounding pharmacists a table that summarizes some of the semisolid lipophilic vehicles, such as creams water/oil, and ointments, that can be used for the formulation of topical treatments., (Copyright© by International Journal of Pharmaceutical Compounding, Inc.)

This study describes a new method for the preparation of extemporaneous paracetamol-based suspensions for pediatric and adult patients. This method allows the preparation of extemporaneous suspensions up to concentrations of 50 mg/mL by using a liquid base, named "Puccini". A high-pressure liquid chromatographic method was developed and validated for the determination of chemical stability of paracetamol when the formulations were stored at 4°C and 25°C. The chemical stability of the active pharmaceutical ingredient in the base was demonstrated for more than 90 days. Visual analyses of the formulations showed a phenomenon of precipitation at both storage temperatures, but the simple agitation of the formulations before its use re-established the formation of homogeneous suspensions., (Copyright© by International Journal of Pharmaceutical Compounding, Inc.)

Pharmaceutical compounding has a crucial role for the health of patients, allowing the preparation of formulation out of market or for a personalized therapy. This study is aimed to conduct a screening of possible ready-to-use hydrophilic vehicles for the preparation of topical dosage forms. Incorporation tests of several active pharmaceutical ingredients were performed, and the physical stability of the extemporaneous formulations was assessed by performing an accelerated centrifuge test. The results showed that it was possible to realize several physically stable topical medications without using special equipment or instruments, guaranteeing a fast and repeatable preparation process. The goal of this work is to provide compounding pharmacists a table that summarizes some of the possible vehicles that can be used for the formulation of topical treatments., (Copyright© by International Journal of Pharmaceutical Compounding, Inc.)

Minoxidil is one of the most employed active pharmaceutical ingredients for the  treatment of androgenetic alopecia. The authors propose a new method for production of minoxidil lotions using Aloplus Total. The latter is a propylene glycol-free liquid base in which the presence of hydroxypropyl-ß-cyclodextrin and ethanol allows the solubilization of high drug amounts. Minoxidil intrinsic solubility in the base was determined, and a comprehensive chemical and physical stability study was conducted on 8% w/w minoxidil lotions. Incorporation tests of different active pharmaceutical ingredients that can be combined to 5% w/w minoxidil were also carried out. The analyses showed that minoxidil intrinsic solubility in the new base was 85.93 mg/mL ± 4.17 mg/mL (8.64% w/w ± 0.42% w/w) at 25°C, and the topical lotions were found to be physically and chemically stable for more than 180 days when stored at 25°C or 40°C. Incorporation tests of several active pharmaceutical ingredients also were successful, indicating that Aloplus Total is a liquid vehicle also useful for the preparation of minoxidil-based topical lotions for a synergistic treatment of androgenetic alopecia., (Copyright© by International Journal of Pharmaceutical Compounding, Inc.)

Omeprazole is the progenitor of proton pump inhibitors. It is used for the treatment of ulcer and gastroesophageal reflux in dosages ranging from 10 mg/day to 40 mg/day, calibrated according to the patient's age and body weight. In this study, the authors provide a report on the preparation of an extemporaneous liquid formulation of omeprazole using fast oral solution Chopin a hydroxypropyl-?-cyclodextrin liquid base (pH 8 to 9) that is able to solubilize the drug. A solubility study of the drug in the liquid vehicle and a physical-chemical stability study of the 1-mg/mL formulation at 4°C and 25°C were performed. Analyses were carried out by using a high-pressure liquid chromatographic analytical method. Results showed that the intrinsic solubility of the drug in Chopin base was 5.33 mg/mL ± 0.23 mg/mL at 25°C and that omeprazole was chemically stable when the formulation was stored at 4°C over a period of 3 months, while its shelf life at 25°C was only 9 days. This study has demonstrated that the resulting liquid formulation is suitable for all patients, in particular children or adults who are unable to take other pharmaceutical dosage forms, which overcomes the limitations of the medicines currently available on the market., (Copyright© by International Journal of Pharmaceutical Compounding, Inc.)

Minoxidil is a vasodilator drug generally employed for the treatment of various forms of alopecia. In this article, the authors propose an alternative to the formulation reported in the British Pharmacopoeia for the realization of topical minoxidil -based solutions using ALOPLUS FAST. This liquid vehicle is an ethanol- and propylene glycol-free base which allows the complete solubilization of minoxidil, thanks to the presence of hydroxypropyl-ß-cyclodextrin. Solubility and chemical stability studies of the active ingredient in the formulation at a concentration of 5% w/w and physical stability studies of this extemporaneous preparation are reported. Incorporation tests of various active pharmaceutical ingredients that can be combined with minoxidil for alopecia synergic treatment have been carried out. Analyses were performed by using a high-pressure liquid chromatography analytical method. The results showed that the intrinsic solubility of the drug in the liquid base was 62.37 mg/mL ± 0.85 mg/mL (5.24 w/w ± 0.07% w/w) at 25°C; minoxidil was chemically stable in ALOPLUS FAST; and the formulation was physically stable for more than six months, under different storage conditions. Incorporation tests of several active pharmaceutical ingredients in 2% to 4% w/w minoxidil formulations were successful as well., (Copyright© by International Journal of Pharmaceutical Compounding, Inc.)