During the past few years, silver nanoparticles (AgNPs) became one of the most investigated and explored nanotechnology-derived nanostructures, given the fact that nanosilver-based materials proved to have interesting, challenging, and promising characteristics suitable for various biomedical applications. Among modern biomedical potential of AgNPs, tremendous interest is oriented toward the therapeutically enhanced personalized healthcare practice. AgNPs proved to have genuine features and impressive potential for the development of novel antimicrobial agents, drug-delivery formulations, detection and diagnosis platforms, biomaterial and medical device coatings, tissue restoration and regeneration materials, complex healthcare condition strategies, and performance-enhanced therapeutic alternatives. Given the impressive biomedical-related potential applications of AgNPs, impressive efforts were undertaken on understanding the intricate mechanisms of their biological interactions and possible toxic effects. Within this review, we focused on the latest data regarding the biomedical use of AgNP-based nanostructures, including aspects related to their potential toxicity, unique physiochemical properties, and biofunctional behaviors, discussing herein the intrinsic anti-inflammatory, antibacterial, antiviral, and antifungal activities of silver-based nanostructures.

/pdf/biomedical-applications-of-silver-nanoparticles-an-up-to-1rjmcs1uea.pdf

Biomedical Applications of Silver Nanoparticles: An Up-to-Date Overview

Drugs with low water solubility are predisposed to poor and variable oral bioavailability and, therefore, to variability in clinical response, that might be overcome through an appropriate formulation of the drug. Polymorphs (anhydrous and solvate/hydrate forms) may resolve these bioavailability problems, but they can be a challenge to ensure physicochemical stability for the entire shelf life of the drug product. Since clinical failures of polymorph drugs have not been uncommon, and some of them have been entirely unexpected, the Food and Drug Administration (FDA) and the International Conference on Harmonization (ICH) has required preliminary and exhaustive screening studies to identify and characterize all the polymorph crystal forms for each drug. In the past, the polymorphism of many drugs was detected fortuitously or through manual time consuming methods; today, drug crystal engineering, in particular, combinatorial chemistry and high-throughput screening, makes it possible to easily and exhaustively identify stable polymorphic and/or hydrate/dehydrate forms of poorly soluble drugs, in order to overcome bioavailability related problems or clinical failures. This review describes the concepts involved, provides examples of drugs characterized by poor solubility for which polymorphism has proven important, outlines the state-of-the-art technologies and discusses the pertinent regulations.

/pdf/polymorph-impact-on-the-bioavailability-and-stability-of-38yeleuwfb.pdf

Polymorph Impact on the Bioavailability and Stability of Poorly Soluble Drugs

Mesoporous silica nanoparticles for therapeutic/diagnostic applications.

Nanotechnology-based drug delivery systems offer an unprecedented opportunity for tumor targeting. Nanocrystals are carrier-free crystalline nanosized solid drug particles. Due to high drug loading (as high as 100%), and being free of organic solvents or surfactants or polymers or solubilizing chemicals, nanocrystals have attracted great attention in the field of drug delivery for treatment of various cancers. Additionally, the hybrid or multifunctional nanocrystal has been extensively investigated for applications in experimental as well as clinical settings to improve delivery efficiency of therapeutic and diagnostic agents. This review gives an overview of recent advances and current status of nanocrystals, especially with respect to the method of preparations, physicochemical characterizations, in vitro/in vivo performance, scale-up techniques and applications in the field of drug delivery for different tumor targeting. Recently much attention has been given to multifunctional nanocrystals showing the capability to codeliver multiple components that target the drug delivery by surface functionalization, performing therapy as well as diagnosis. Preparative techniques like high-pressure homogenization, precipitation, and media milling have been known to show large-scale production of nanocrystals. High therapeutic applications of nanoparticles enable its administration through various routes like oral, parenteral, pulmonary, dermal, and ocular. Along with preparation and characterization, this review will dwell on the progress involved with multifunctional nanocrystals for cancer therapy and theranostics. Most available results in multifunctional nanocrystal targeting rely upon in vitro and animal models, which do not match the actual environment of the tumor in the body, which is one of the major obstacles. Other challenges faced when it comes to nanocrystals are scale-up and reproducibility. In addition, potential problems and possible future research directions for the advancement of newer techniques of multifunctional nanocrystals that make them highly suitable for tumor targeted are highlighted in this review.

Multifunctional nanocrystals for cancer therapy: a potential nanocarrier

https://repositorium.sdum.uminho.pt/bitstream/1822/46342/1/document_46739_1.pdf

Micro- and nano bio-based delivery systems for food applications: In vitro behavior

https://cyberleninka.org/article/n/380530.pdf

Pharmaceutical particle technologies: An approach to improve drug solubility, dissolution and bioavailability

β-Lapachone has drawn increasing attention as an anti-inflammatory and anti-cancer drug. However, its oral bioavailability has not been yet assessed, which might be useful to develop efficient dosage forms possibly required for non-clinical and clinical studies and future market. The aim of the present study was thus to investigate pharmacokinetic properties of β-lapachone as well as its first-pass metabolism in the liver, and small and large intestines after oral administration to measure the absolute bioavailability in rats. A sensitive HPLC method was developed to evaluate levels of β-lapachone in plasma and organ homogenates. The drug degradation profiles were examined in plasma to assess the stability of the drug and in liver and intestinal homogenates to evaluate first-pass metabolism. Pharmacokinetic profiles were obtained after oral and intravenous administration of β-lapachone at doses of 40 mg/kg and 1.5 mg/kg, respectively. The measured oral bioavailability of β-lapachone was 15.5%. The considerable degradation of β-lapachone was seen in the organ homogenates but the drug was quite stable in plasma. In conclusion, we suggest that the fairly low oral bioavailability of β-lapachone may be resulted from the first-pass metabolic degradation of β-lapachone in the liver, small and large intestinal tracts and its low aqueous solubility.

/pdf/preclinical-pharmacokinetic-evaluation-of-b-lapachone-3kpf5ggs1f.pdf

Preclinical Pharmacokinetic Evaluation of β-Lapachone: Characteristics of Oral Bioavailability and First-Pass Metabolism in Rats

This study investigated the interaction between polydeoxyribonucleotide (PDRN) and several ionic and nonionic isotonic agents, thickeners and a preservative that were employed as excipients in ophthalmic preparations. Interaction of each individual excipient and PDRN aqueous solution was evaluated by analyzing their rheological properties. Rheological properties of PDRN solutions were evaluated by dynamic oscillatory shear tests and values of elastic modulus (G'), viscous modulus (G″) and loss tangent (tan δ) were used to assess the relative changes in viscoelastic properties. At given concentrations, sodium chloride was found to show alteration in viscoelastic properties of PDRN solution while nonionic isotonic agents like d-glucose and d-sorbitol did not alter them. Similarly, nonionic water soluble polymers like polyvinylpyrrolidone (PVP) and hydroxypropyl methylcellulose (HPMC) also did not interact with PDRN to alter the viscoelastic properties. However, there were changes observed when carbopol 940 was used as a thickener. Therefore, PDRN was found to interact with ionic excipients and the interactions were negligible when nonionic materials were examined, which suggests that nonionic excipients are suitable to be formulated with PDRN.

Viscoelastic interactions between polydeoxyribonucleotide and ophthalmic excipients.

Pharmaceutical excipients (PEs) are an essential part of drug products to make them have desirable characteristics. Most pharmaceutical excipients have been considered as biologically inert. However, recent studies showed that PEs affect pharmacokinetic behaviors of drugs in several manners when absorbed through gastrointestinal (GI) tract. For example, oral administration of the excipients such as nonionic surfactants could modulate cytochrome P450 enzymes, in GI tract and liver, and p-glycoprotein (p-gp) leading to changes in pharmacokinetic characteristics in vitro and in vivo. Sulfotransferase (SULT) is one of the phase II metabolism enzymes mainly found in the liver and small intestine and catalyzes the transfer of sulfuryl groups from 3'-phosphoadenosine 5'-phosphosulfate (PAPS) to hydroxyl or amino groups of the compounds. The biological functions of SULT include metabolism and detoxification of xenobiotics by sulfation. It can therefore be anticipated that inhibitors or enhancers of SULT alter the metabolic profiles of substrate drugs susceptive to the enzymes which may decrease or increase the bioavailability of the drug. For example, SULT1A1 and SULT1A3 play important roles in the pre-systemic inactivation of β2 agonists in the liver and intestine. Thus, inhibition of SULTs can lead to an increase in the bioavailability of β2 agonists. In this study, we attempted to investigate the possibility of the modulation of SULT by a wide range of PEs frequently used in the formulation of oral drug delivery systems to improve the bioavailability of drugs that are extensively degraded by SULTs.

Iksoo Kim

Papers

Pharmaceutical particle technologies: An approach to improve drug solubility, dissolution and bioavailability

Preclinical Pharmacokinetic Evaluation of β-Lapachone: Characteristics of Oral Bioavailability and First-Pass Metabolism in Rats

Viscoelastic interactions between polydeoxyribonucleotide and ophthalmic excipients.

In vitro Metabolic Modulation of Aryl Sulfotransferases by Pharmaceutical Excipients