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International Journal of Pharmaceutics Sep 2021Due to the very low bioavailability of drugs administered to the surface of the eyeball, issues related to the formulation of an ophthalmic drug pose a technological... (Review)
Review
Due to the very low bioavailability of drugs administered to the surface of the eyeball, issues related to the formulation of an ophthalmic drug pose a technological challenge. The essence of an ophthalmic drug is the selection of an appropriate active substance (API), but also auxiliary substances that determine the desired drug quality and API availability. The ophthalmic drug is not only classic eye drops. Therefore, on the basis of the literature data, the properties and application of auxiliary substances increasing the pharmaceutical availability of API, improving the penetration of API into the eye structures and modifying the viscosity of eye drops were characterized. The possibility of chemical modification of API and the use of prodrugs in ophthalmic drug forms was also noted. Taking into account the progress in the field of ophthalmic drug formulation, the use of multi-compartment systems (lipid particles, nanoparticles, microparticles, liposomes, niosomes, dendrimers) and modern ophthalmic drug delivery systems (inserts, implants, microneedles, contact lenses, ionophoretic systems) have been indicated. Examples of solutions already used by manufacturers, as well as those in the phase of laboratory or clinical trials, were indicated.
Topics: Biological Availability; Drug Compounding; Drug Delivery Systems; Eye; Ophthalmic Solutions; Ophthalmology
PubMed: 34400274
DOI: 10.1016/j.ijpharm.2021.121012 -
Molecules (Basel, Switzerland) Apr 2024Curcumin (CCM) is a polyphenol compound extracted from the turmeric rhizome. It has various biological activities, including antibacterial, anti-inflammatory,... (Review)
Review
Curcumin (CCM) is a polyphenol compound extracted from the turmeric rhizome. It has various biological activities, including antibacterial, anti-inflammatory, anti-cancer, and antioxidant. Due to its diverse activities, it is often used by researchers to study the therapeutic effects on various diseases. However, its poor solubility leads to poor bioavailability, and it is necessary to increase the water solubility with the help of carriers to improve the therapeutic effect. Gastrointestinal disease is a major global health problem that continues to affect human health. In this review, we have summarized the possible mechanism and therapeutic effect of CCM in various gastrointestinal diseases, and the improvement in the curative effect of CCM with nanopreparation. Finally, we concluded that there have been many clinical trials of CCM in combination with other drugs for the treatment of gastrointestinal disease, but so far, few have used CCM nanomaterials for treatment. Although in vitro and preclinical experiments have shown that nanopreparations can improve the efficacy of CCM, there are still insufficient studies on the safety of carriers.
Topics: Humans; Curcumin; Anti-Bacterial Agents; Antioxidants; Biological Availability; Gastrointestinal Diseases
PubMed: 38611938
DOI: 10.3390/molecules29071659 -
Pharmacological Research Sep 2023Organ-on-chip (OoC) technology has led to in vitro models with many new possibilities compared to conventional in vitro and in vivo models. In this review, the potential... (Review)
Review
Organ-on-chip (OoC) technology has led to in vitro models with many new possibilities compared to conventional in vitro and in vivo models. In this review, the potential of OoC models to improve the prediction of human oral bioavailability and intrinsic clearance is discussed, with a focus on the functionality of the models and the application in current drug development practice. Multi-OoC models demonstrating the application for pharmacokinetic (PK) studies are summarized and existing challenges are identified. Physiological parameters for a minimal viable platform of a multi-OoC model to study PK are provided, together with PK specific read-outs and recommendations for relevant reference compounds to validate the model. Finally, the translation to in vivo PK profiles is discussed, which will be required to routinely apply OoC models during drug development.
Topics: Humans; Models, Biological; Drug Development; Biological Availability; Microphysiological Systems
PubMed: 37473876
DOI: 10.1016/j.phrs.2023.106853 -
International Journal of Nanomedicine 2024Nanosuspensions have garnered recent attention as a promising strategy for mitigating the bioavailability challenges of hydrophobic drugs, particularly those... (Review)
Review
Nanosuspensions have garnered recent attention as a promising strategy for mitigating the bioavailability challenges of hydrophobic drugs, particularly those characterized by poor solubility in both aqueous and organic environments. Addressing solubility issues associated with poorly water-soluble drugs has largely resolved the need to enhance drug absorption and bioavailability. As mucosal formulations and topical administration progress in the future, nanosuspension drug delivery, straightforward formulation techniques, and versatile applications will continue to be subjects of interest. Nanosuspensions have undergone extensive scrutiny in preparation for topical applications, encompassing ocular, pulmonary, and dermal usage. Among the numerous methods aimed at improving cutaneous application, nanocrystals represent a relatively recent yet profoundly intriguing approach. Despite the increasing availability of various nanosuspension products, primarily designed for oral administration, only a limited number of studies have explored skin permeability and drug accumulation in the context of nanosuspensions. Nevertheless, the scant published research unequivocally underscores the potential of this approach for enhancing cutaneous bioavailability, particularly for active ingredients with low to medium solubility. Nanocrystals exhibit increased skin adhesiveness in addition to heightened saturation solubility and dissolution rate, thereby augmenting cutaneous distribution. The article provides a comprehensive overview of nanosuspensions for topical application. The methodology employed is robust, with a well-defined experimental design; however, the limited sample size raises concerns about the generalizability of the findings. While the results demonstrate promising outcomes in terms of enhanced drug delivery, the discussion falls short of addressing certain limitations. Additionally, the references largely focus on recent studies, but a more diverse inclusion of historical perspectives could offer a more holistic view of the subject.
Topics: Humans; Suspensions; Drug Delivery Systems; Biological Availability; Nanoparticles; Administration, Oral; Solubility; Particle Size
PubMed: 38293608
DOI: 10.2147/IJN.S447429 -
Molecules (Basel, Switzerland) Sep 2020Food protein-derived bioactive peptides are recognized as valuable ingredients of functional foods and/or nutraceuticals to promote health and reduce the risk of chronic... (Review)
Review
Food protein-derived bioactive peptides are recognized as valuable ingredients of functional foods and/or nutraceuticals to promote health and reduce the risk of chronic diseases. However, although peptides have been demonstrated to exert multiple benefits by biochemical assays, cell culture, and animal models, the ability to translate the new findings into practical or commercial uses remains delayed. This fact is mainly due to the lack of correlation of in vitro findings with in vivo functions of peptides because of their low bioavailability. Once ingested, peptides need to resist the action of digestive enzymes during their transit through the gastrointestinal tract and cross the intestinal epithelial barrier to reach the target organs in an intact and active form to exert their health-promoting properties. Thus, for a better understanding of the in vivo physiological effects of food bioactive peptides, extensive research studies on their gastrointestinal stability and transport are needed. This review summarizes the most current evidence on those factors affecting the digestive and absorptive processes of food bioactive peptides, the recently designed models mimicking the gastrointestinal environment, as well as the novel strategies developed and currently applied to enhance the absorption and bioavailability of peptides.
Topics: Animals; Biological Availability; Food; Gastrointestinal Tract; Humans; Intestinal Absorption; Models, Biological; Peptides
PubMed: 33003506
DOI: 10.3390/molecules25194479 -
Molecules (Basel, Switzerland) Aug 2023Herbal medicines have gained recognition among physicians and patients due to their lower adverse effects compared to modern medicines. They are extensively used to... (Review)
Review
Herbal medicines have gained recognition among physicians and patients due to their lower adverse effects compared to modern medicines. They are extensively used to treat various diseases, including cancer, cardiovascular issues, chronic inflammation, microbial contamination, diabetes, obesity, and hepatic disorders, among others. Unfortunately, the clinical application of herbal medicines is limited by their low solubility and inadequate bioavailability. Utilizing herbal medicines in the form of nanocrystals (herbal medicine nanocrystals) has shown potential in enhancing solubility and bioavailability by reducing the particle size, increasing the specific surface area, and modifying the absorption mechanisms. Multiple studies have demonstrated that these nanocrystals significantly improve drug efficacy by reducing toxicity and increasing bioavailability. This review comprehensively examines therapeutic approaches based on herbal medicine nanocrystals. It covers the preparation principles, key factors influencing nucleation and polymorphism control, applications, and limitations. The review underscores the importance of optimizing delivery systems for successful herbal medicine nanocrystal therapeutics. Furthermore, it discusses the main challenges and opportunities in developing herbal medicine nanocrystals for the purpose of treating conditions such as cancer, inflammatory diseases, cardiovascular disorders, mental and nervous diseases, and antimicrobial infections. In conclusion, we have deliberated regarding the hurdles and forthcoming outlook in the realm of nanotoxicity, in vivo kinetics, herbal ingredients as stabilizers of nanocrystals, and the potential for surmounting drug resistance through the utilization of nanocrystalline formulations in herbal medicine. We anticipate that this review will offer innovative insights into the development of herbal medicine nanocrystals as a promising and novel therapeutic strategy.
Topics: Humans; Herbal Medicine; Plants, Medicinal; Biological Availability; Nanoparticles; Plant Extracts
PubMed: 37687199
DOI: 10.3390/molecules28176370 -
International Journal of Molecular... Jun 2021Encapsulation of cargoes in nanocontainers is widely used in different fields to solve the problems of their solubility, homogeneity, stability, protection from unwanted... (Review)
Review
Encapsulation of cargoes in nanocontainers is widely used in different fields to solve the problems of their solubility, homogeneity, stability, protection from unwanted chemical and biological destructive effects, and functional activity improvement. This approach is of special importance in biomedicine, since this makes it possible to reduce the limitations of drug delivery related to the toxicity and side effects of therapeutics, their low bioavailability and biocompatibility. This review highlights current progress in the use of lipid systems to deliver active substances to the human body. Various lipid compositions modified with amphiphilic open-chain and macrocyclic compounds, peptide molecules and alternative target ligands are discussed. Liposome modification also evolves by creating new hybrid structures consisting of organic and inorganic parts. Such nanohybrid platforms include cerasomes, which are considered as alternative nanocarriers allowing to reduce inherent limitations of lipid nanoparticles. Compositions based on mesoporous silica are beginning to acquire no less relevance due to their unique features, such as advanced porous properties, well-proven drug delivery efficiency and their versatility for creating highly efficient nanomaterials. The types of silica nanoparticles, their efficacy in biomedical applications and hybrid inorganic-polymer platforms are the subject of discussion in this review, with current challenges emphasized.
Topics: Biological Availability; Drug Carriers; Drug Compounding; Ligands; Lipids; Nanoparticles; Porosity; Silicon Dioxide
PubMed: 34209023
DOI: 10.3390/ijms22137055 -
International Journal of Molecular... Jan 2024Drugs based on peptides and proteins (PPs) have been widely used in medicine, beginning with insulin therapy in patients with diabetes mellitus over a century ago.... (Review)
Review
Drugs based on peptides and proteins (PPs) have been widely used in medicine, beginning with insulin therapy in patients with diabetes mellitus over a century ago. Although the oral route of drug administration is the preferred one by the vast majority of patients and improves compliance, medications of this kind due to their specific chemical structure are typically delivered parenterally, which ensures optimal bioavailability. In order to overcome issues connected with oral absorption of PPs such as their instability depending on digestive enzymes and pH changes in the gastrointestinal (GI) system on the one hand, but also their limited permeability across physiological barriers (mucus and epithelium) on the other hand, scientists have been strenuously searching for novel delivery methods enabling peptide and protein drugs (PPDs) to be administered enterally. These include utilization of different nanoparticles, transport channels, substances enhancing permeation, chemical modifications, hydrogels, microneedles, microemulsion, proteolytic enzyme inhibitors, and cell-penetrating peptides, all of which are extensively discussed in this review. Furthermore, this article highlights oral PP therapeutics both previously used in therapy and currently available on the medical market.
Topics: Humans; Gastrointestinal Agents; Insulin; Cell-Penetrating Peptides; Biological Availability; Hydrogels
PubMed: 38255888
DOI: 10.3390/ijms25020815 -
Journal of Pharmacy & Pharmaceutical... 2019Particle engineering has become a hot topic in the field of modified-release delivery systems during last decades. It has a wide range of pharmaceutical applications and... (Review)
Review
Particle engineering has become a hot topic in the field of modified-release delivery systems during last decades. It has a wide range of pharmaceutical applications and is a bridge linking between drugs and drug delivery systems. Particles are an important part of many dosage forms and viewed as a carrier of drugs. Their size, shape, crystalline form, and structure directly affect the stability and releasing pattern of drugs. Engineering size or modifying particles by forming porous, core-shell, or skeleton structures can realize the development and utilization of functionally modified release systems (including fast-release systems, sustained-release systems, and targeted-release systems). However, there are certain problems in the practical application, such as bitter taste and coating damage. Combining with some polymer or lipid materials to form core-shell or embedded structures is considered as the key to taste masking. And, using cushioning agents is proven to be effective in preserving the integrity of the functional coating film of multiparticulates during tableting. To sum up, this review, from a particle engineering point, expounds the influence of different factors on the functionality of particles and offers some useful comments and suggestions for industry personnel.
Topics: Biological Availability; Drug Delivery Systems; Particle Size; Pharmaceutic Aids; Tablets; Technology, Pharmaceutical
PubMed: 31026393
DOI: 10.18433/jpps30253 -
International Journal of Molecular... Mar 2022Several plant-based nanoscale-encapsulated antioxidant compounds (rutin, myricetin, β-carotene, fisetin, lycopene, quercetin, genkwanin, lutein, resveratrol,... (Review)
Review
Several plant-based nanoscale-encapsulated antioxidant compounds (rutin, myricetin, β-carotene, fisetin, lycopene, quercetin, genkwanin, lutein, resveratrol, eucalyptol, kaempferol, glabridin, pinene, and whole-plant bio-active compounds) are briefly introduced in this paper, along with their characteristics. Antioxidants' bioavailability has become one of the main research topics in bio-nanomedicine. Two low patient compliance drug delivery pathways (namely, the oral and topical delivery routes), are described in detail in this paper, for nanoscale colloidal systems and gel formulations. Both routes and/or formulations seek to improve bioavailability and maximize the drug agents' efficiency. Some well-known compounds have been robustly studied, but many remain elusive. The objective of this review is to discuss recent studies and advantages of nanoscale formulations of plant-derived antioxidant compounds.
Topics: Antioxidants; Biological Availability; Humans; Plants; Quercetin; Resveratrol; Rutin
PubMed: 35409001
DOI: 10.3390/ijms23073638