Recent advancements in drug nanocrystals: Innovation in formulation and drug delivery

Chapter 11 - Drug nanocrystals as nanocarrier-based drug delivery systems

AI Innovations in Drug Delivery and Pharmaceutical Sciences: Advancing Therapy through Technology offers a comprehensive exploration of how artificial intelligence (AI) is revolutionizing the pharmaceutical and healthcare sectors. This book addresses the AI’s role in drug discovery, development, and delivery, highlighting applications in personalized medicine, nanotechnology, and clinical trials. It also covers AI’s impact on community and hospital pharmacy, herbal medicine, and drug product design. Each chapter examines the use of AI in optimizing drug processes, from designing innovative therapies to improving regulatory compliance and future trends in pharmaceutical technology. This insightful resource is invaluable for researchers, pharmaceutical professionals, and healthcare innovators aiming to advance therapeutic outcomes through AI. Key Features: - Comprehensive coverage of AI applications in drug discovery, delivery, and design. - Insights into AI-driven personalized medicine and nanotechnology. - Regulatory perspectives on AI in drug delivery and medical devices. - Future trends and innovations in AI for pharmaceutical technology.

Drug nanocrystals: Fabrication methods and promising therapeutic applications

Many compounds with better therapeutic efficiency were neglected for formulation development and delivery in conventional drug delivery approaches. Traditional strategies for addressing this issue include salt formulation, solubilization, complexation, and liposome formation. The modern nanocrystal technology potentially addresses poor bioavailability, low saturation solubility, and dissolution rate of therapeutic moieties. Drug nanocrystals, known for their simplicity in preparation and general applicability, consist of pure active pharmaceutical ingredient compared to other nanoparticulate systems. As polymeric nanoparticle-based drug delivery systems are to be considered for their level of toxicity and drug loading capacity, nanocrystals are receiving much attention nowadays. Production techniques of such nanocrystals, comprised pearl milling, high-pressure homogenization, and precipitation, alter superior physicochemical properties such as increased solubility, permeability, stability, and amorphization. This further aids in the targeted drug delivery to the injured site with minimal elucidation of toxicity in the surrounding normal cells. With a better biological understanding, drug nanocrystals are being utilized as a potent nanocarrier drug delivery system to address the physicochemical barriers of clinically meaningful drugs.

Chapter 22 - Nanocrystals in the drug delivery system

Chapter 10 - Drug nanocrystals as drug delivery systems

0,1,2,3D nanostructures, types of bulk nanostructured materials, and drug nanocrystals: An overview

Nanomedicines for ocular NSAIDs: safety on drug delivery

In article number 1604508, Dongfei Liu, Hélder A. Santos, and co-workers fabricated an optimal nano-innano vector, consisting of a drug nanocrystal core and a polymer shell. The favorable features of both polymer nanoparticles and drug nanocrystals were inherited by the obtained core/shell nanovector. The half maximal inhibitory concentration value of the core/shell nanovector was over 50 times lower than that of conventional particles.

In our previous studies, drug nanocrystals were directly prepared by solution crystallization, possessing uniform particle size and morphology suitable for intravenous (IV) injection. These nanocrystals accumulated in a small percentage of their injected dose in tumor-bearing mice but showed similar anti-tumor effectiveness and much-reduced side effects compared with current commercial solubilized and encapsulated delivery systems. In this study, we aimed to delineate possible controlling factors for the pharmacokinetics (PK) and biodistribution behaviors of paclitaxel (PTX) nanocrystals tested in mice by applying physiologically based pharmacokinetics (PBPK) modeling, coupled with pharmacodynamics (PD) simulation, to the data. Our results show that clearance of the drug plays a significant, if not the most important, role in determining tissue distribution, including tumor accumulation of PTX nanocrystals. Surface treatment of drug nanocrystals with polymeric surfactants also appeared to affect PK profiles and PD outcomes. Importantly, when scaled to model human parameters, our PK/PD simulations suggest that drug distribution in humans, as opposed to animal models, was significantly influenced by tissue partitioning rather than drug clearance. This finding could facilitate the design and development of future drug delivery systems. Drug nanocrystals deposited in tissues, including tumors, could therefore act as depots, releasing the drug back into the circulation, possibly contributing to extended treatment, as well as any detrimental effects.

Cancer accounts for the high mortality rate and limits the life expectancy of an individual. As per the WHO report of 2020, cancer accounts for >10 million deaths globally. Scientists are continuously pitching toward the development of novel techniques to combat this menace and enhance the efficacy of prevailing molecules. In the early phases of the drug development process, >40% of promising new therapeutic molecules are hydrophobic. Low aqueous solubility results in compromised bioavailability on administration. This limitation is a major drawback for the therapeutic use of anticancer drugs. Drug nanocrystals (NCs) have sparked a lot of interest in drug delivery. This might be due to their excellent physicochemical characteristics like tailored dissolution, high drug loading efficiency, extended circulation period, and high structural stability. There are 'n' a number of the characteristics that make drug nanocrystals a promising formulation for the treatment of cancer. In the last few years, many hydrophobic or lipophilic drugs like camptothecin, paclitaxel, cyclosporin, busulfan, and thymectacin have been formulated as drug nanocrystals against anticancer therapeutics. Various formulation technologies have been developed in conjunction with nanocrystal development. This includes top-down approaches, bottom-up approaches, as well as combination technology. In this article, we will focus on the various manufacturing processes, biological fate and therapeutic applications of NCs, and future perspectives in the management of cancer.

Introduction Lung cancer and metastases are major concerns worldwide. Although systemic chemotherapy is the recommended treatment, it is associated with various disadvantages, including nonselective drug distribution and systemic toxicity. In contrast, the pulmonary route ensures the localized delivery of drugs to the lung. Still, the pulmonary route is prone to clearance, limited drug dissolution, and local toxicity to healthy lung cells. Drug nanocrystals provide a potential strategy to enhance the therapeutic efficacy and mitigate the limitations of pulmonary delivery. Areas covered The development and potential application of nanocrystals in pulmonary delivery, their role in overcoming associated barriers, and strategies for site-specific and stimuli-responsive pulmonary delivery are outlined. This review also traces different in-vitro pulmonary models for assessments of the performance of drug nanocrystals and nanocrystals loaded carriers in pulmonary delivery. Expert opinion Enhanced stability, high aerosolization performance, better particle size distribution, improved penetration, sustained release of the drug, and minimal excipients usage makes drug nanocrystal an ideal candidate for pulmonary delivery. Besides, drug nanocrystals may provide selective cellular internalization with minimum clearance and maximum deposition. Furthermore, surface modified nanocrystals and nanocrystals in nanocarriers can exhibit a more prolonged, and site-specific release of the drug to cancer cells in the lungs.

Chapter 11 - Analytical tools for reliable in vitro and in vivo performance testing of drug nanocrystals

Novel drug delivery typically involves nanotechnology-based approaches that require multidisciplinary efforts combining the fields of pharmaceutics, physical chemistry, polymer science, bioconjugate chemistry, and molecular biology. This chapter discusses various aspects of novel drug delivery. The first part of the chapter is especially focused on targeted drug delivery approaches, such as passive targeting and active targeting. The later part of the chapter provides valuable insight into various nanopharmaceuticals employed as novel drug delivery systems: drug nanocrystals, polymeric nanoparticles, liposomes, and niosomes are discussed as examples.KeywordsTargeted drug deliveryNanomedicineNanoparticlesPharmaceutical nanotechnologyNanocrystal technology

A carrier-free method for delivery of a hydrophobic drug in its pure form, using nanocrystals (nanosized crystals), is proposed. To demonstrate this technique, nanocrystals of a hydrophobic photosensitizing anticancer drug, 2-devinyl-2-(1-hexyloxyethyl)pyropheophorbide (HPPH), have been synthesized using the reprecipitation method. The resulting drug nanocrystals were monodispersed and stable in aqueous dispersion, without the necessity of an additional stabilizer (surfactant). As shown by confocal microscopy, these pure drug nanocrystals were taken up by the cancer cells with high avidity. Though the fluorescence and photodynamic activity of the drug were substantially quenched in the form of nanocrystals in aqueous suspension, both these characteristics were recovered under in vitro and in vivo conditions. This recovery of drug activity and fluorescence is possibly due to the interaction of nanocrystals with serum albumin, resulting in conversion of the drug nanocrystals into the molecular form. This was confirmed by demonstrating similar recovery in presence of fetal bovine serum (FBS) or bovine serum albumin (BSA). Under similar treatment conditions, the HPPH in nanocrystal form or in 1% Tween-80/water formulation showed comparable in vitro and in vivo efficacy.