Dear Colleagues,

Over the last ten years, the number of poorly soluble drugs (biopharmaceutical specification (BCS) class II and class IV) has steadily increased. Progress in high-throughput screening (HTS) methods has revealed an even greater amount of newly discovered drugs that have a poor water solubility, and poor solubility in water correlates with poor bioavailability. If there is no method for improving drug solubility, it cannot be absorbed from the gastrointestinal tract (GIT) into the bloodstream and reach the site of action. The transfer of materials in the nanodimension affects their physical properties, which are used in the development of  new and innovative pharmaceutical formulation principles for poorly soluble drugs. Drug nanocrystals (i.e., nanosized crystal of parent drug with dimension < 1 μm and exempt of a carrier) represent a great example of nanonization for oral and intravenous (IV) bioavailability enhancement. Due to their success and increasing attention, the first NC products are already in the market. Indeed, conventional drug delivery systems (DDS) solubilize certain poorly soluble drugs but are limited to drugs with certain chemical–physical properties (e.g., solubility in certain organic media, molecular size, or conformation). Additionally, the use of surfactants or cosolvents in traditional DDS may increase side effects due to their relative toxicity. An esterification method can be used to simultaneously increase drug solubility and permeability (BCS drugs class IV), but little consideration is given to the biological effect and/or toxicity of the structural modifications; therefore, derivatives are rarely tested for toxicity, potency, tissue distribution, or elimination. Additionally, the micronization of drug powders to sizes between 1 and 10 μm to increase their surface area, and thus the dissolution velocity, is not sufficient for overcoming bioavailability problems of many very poorly soluble drugs of BCS class II.

Nowadays, drug NCs are increasingly studied as a promising approach owing to many reasons including the (i) increasing number of poor-soluble drugs in drug development process, (ii) pharmacoeconomic value, (iii) easy production, (iv) safe composition. Soon, it could be expected that the drug NCs doped with certain surface proteins will be prepared for targeting a particular tissue (e.g., skin) or cell (e.g., tumor cell). This Special Issue aims to highlight the current state-of-the art of advanced nanocrystal drugs with a special emphasis on BCS class II and class IV. Researchers, industrials, biomedical engineers, technologists, chemists, pharmacists, toxicologists, and healthcare professionals who specialize in nanomedicine, nanotechnology, pharmaceutical formulation, and translational medicine are invited to share their knowledge by contributing original basic, applied, and clinical research articles. Review articles are also encouraged. The manuscripts must be of a high-quality and emphasize the impact of advanced nanocrystal drugs. In vitro, ex vivo, and in vivo assays should be performed using advanced techniques and methods. Innovation using tunable functionalized NCs tested in various mammalian cell lines/types, animal models and a clinical setting will particularly be appreciated:

Potential topics may include, but are not limited to, the following:

• Preparation of NCs (bottom-up approaches, such as precipitation, spray drying, and lyophilization; top-down approaches such as milling methods and high-pressure homogenization; combination approach; stabilization (e.g., with Poloxamer 188);
• Properties of NCs (solubility and saturation solubility enhancement, dissolution and dissolution velocity, permeation, bioavailability, adhesiveness to surface/cell membrane);
• Characterization of NCs (PS, ZP, PDI, XRD, DSC, SEM, TEM, drug content analysis, release behavior studies);
• NCs of BCS class II and BCS class IV;
• Solid or Suspension NCs;
• Topical applications of NCs;
• Tunable functionalization of NCs;
• NCs products in market;
• Clinical trials involving NCs (e.g., Paclitaxel, Ciprofloxacin, Rapamycin)

Prof. Dr. Farid Menaa
Dr. Jamal Moideen Muthu Mohamed
Guest Editors

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Crystals is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

• preparation of NCs NCs of BCS class II and BCS class IV
• properties of NCs
• NCs of BCS class II and BCS class IV
• characterizations of NCs
• solid or suspension NCs
• topical applications of NCs
• NCs products in market
• clinical trials involving NCs