Nanotechnology in Plants.

The integration of nanotechnology in medicine has had a tremendous impact in the past few decades. The discovery of synthesis of nanomaterials (NMs) and their functions as versatile tools promoted various applications in nano-biotechnology and nanomedicine. Although the physical and chemical methods are still considered as commonly used methods, they introduce several drawbacks such as the use of toxic chemicals (solvent, reducing, and capping agents) and poor control of size, size distribution, and morphology, respectively. Additionally, the NMs synthesized in organic solvents and hydrophobic surfactants rapidly aggregate in aqueous solutions or under physiologic conditions, limiting their applications in medicine. Many of the phase-transfer strategies were developed and applied for the transfer of NMs into aqueous solutions. Although great efforts have been put into phase transfers, they mostly include expensive, time-consuming, intensive labor work, multi steps, and complicated procedures.Use of plant extracts in the biological synthesis method offers stark advantages over other biomolecules (protein, enzyme, peptide, and DNA). Plant extracts have been commonly used for food, medicine, NM synthesis, and biosensing. There are many viable techniques developed for the production of plant extracts with various contents based on their simplicity, cost, and the type of extract content. In this chapter, we conduct a comparative study for extract preparation techniques, the use of extracts for metallic single and hybrid nanoparticle (NP) synthesis, and their antimicrobial properties against pathogenic and plant-based bacteria. Graphical Abstract.

Recent expansion of pharmaceutical nanotechnologies and targeting strategies in the field of phytopharmaceuticals for the delivery of herbal extracts and bioactives.

Application of pharmaceutical nanotechnology (nanomedicines) for plant actives and extracts, is gaining a tremendous growth and interest among the scientists. This emerging herbal revolution has headed towards the development of another approaches for the delivery of poorly soluble herbal bioactives and plant extracts for enhancing their bioavailability and efficacy. In the same context, a majority of pharmaceutical nanotechnologies and targeting strategies including phytosomes, nanoparticles, hydrogels, microspheres, transferosomes and ethosomes, self nano emulsifying drug delivery systems (SNEDDS), self micro emulsifying drug delivery systems (SMEDDS) has been applied for the delivery of bioactives and plant extracts and were identified and explored. These pharmaceutical nanotechnologies have been proven to be the most efficient and reliable delivery systems, as these enhance the solubility, absorption, pharmacokinetics, bioavailability and provide protection from toxicity. Considering these aspects, the present review highlights the present scenario related to the expansion of novel herbal formulations utilizing the nanotechnologies and compilation of their delivery types and mechanism, methodology, loaded drug, drug size, entrapment efficiency of drug, in vivo activity and its application. Moreover, this review article provides an understanding of therapeutic efficacy of the herbal medicines to be loaded into the novel drug delivery system for various biomedical applications.

Metal ion-mobilizing additives for comprehensive detection of femtomole amounts of phosphopeptides by reversed phase LC-MS.

It is hypothesized that metal ion-mediated adsorption of phosphorylated peptides on stationary phases of LC-columns is the major cause for their frequently observed poor detection efficiency in LC-MS. To study this phenomenon in more detail, sample solutions spiked with metal ion-mobilizing additives were analyzed by reversed phase µLC-ICP-MS or nanoLC-ESI-MS. Using µLC-ICP-MS, metal ions were analyzed directly as atomic ions. Using electrospray ionization, either metal ion chelates or phosphopeptide standard mixtures injected in subpicomole amounts were analyzed. Deferoxamine, imidazole, ascorbate, citrate, EDTA, and the tetrapeptide pSpSpSpS were tested as sample additives for the interlinked purposes of metal ion-mobilization and improvement of phosphopeptide recovery. Iron probably represents the major metal ion contamination of reversed phase columns. Based on the certified iron level in LC-grade solvents, a daily metal ion load of >10 pmol was estimated for typical nanoLC flow rates. In addition, phosphopeptide fractions from IMAC columns were identified as source for metal ion contamination of the LC column, as demonstrated for Ga(3+)-IMAC. The three metal ion-chelating additives, EDTA, citrate and pSpSpSpS, were found to perform best for improving the LC recovery of multiply phosphorylated peptides injected at subpicomole amounts. The benefits of metal ion-mobilizing LC (mimLC) characterized by metal ion complexing sample additives is demonstrated for three different instrumental setups comprising (a) a nanoUPLC-system with direct injection on the analytical column, (b) a nanoLC system with inclusion of a trapping column, and (c) the use of a HPLC-Chip system with integrated trapping and analytical column.

Quality by design: understanding the formulation variables of a cyclosporine A self-nanoemulsified drug delivery systems by Box-Behnken design and desirability function.

Quality by design (QBD) refers to the achievement of certain predictable quality with desired and predetermined specifications. A very useful component of the QBD is the understanding of factors and their interaction effects by a desired set of experiments. The present project deals with a case study to understand the effect of formulation variables of nanoemulsified particles of a model drug, cyclosporine A (CyA). A three-factor, three-level design of experiment (DOE) with response surface methodology (RSM) was run to evaluate the main and interaction effect of several independent formulation variables that included amounts of Emulphor El-620 (X(1)), Capmul MCM-C8 (X(2)) and 20% (w/w) CyA in sweet orange oil (X(3)). The dependent variables included nanodroplets size (Y(1)), nanoemulsions turbidity (Y(2)), amounts released after 5 and 10min (Y(3), Y(4)), emulsification rate (Y(5)) and lag time (Y(6)). A desirability function was used to minimize lag time and to maximize the other dependent variables. A mathematical relationship, Y(5)=9.09-0.37X(1)+0.37X(2)-0.45X(3)+0.732X(1)X(2)-0.62X(1)X(3)+0.3X(2)X(3)+0.02X(1)(2)-0.28X(2)(2)+0.471X(3)(2) (r(2)=0.92), was obtained to explain the effect of all factors and their colinearities on the emulsification rate. The optimized nanodroplets were predicted to yield Y(1), Y(2), Y(3), Y(4), Y(5) and Y(6) values of 42.1nm, 50.6NTU, 56.7, 107.2, 9.3%/min and 3.5min, respectively, when X(1), X(2), and X(3) values were 36.4, 70 and 10mg, respectively. A new batch was prepared with these levels of the independent variables to yield Y(1)-Y(6) values that were remarkably close to the predicted values. In conclusion, this investigation demonstrated the potential of QBD in understanding the effect of the formulation variables on the quality of CyA self-nanoemulsified formulations.

Ultra-low flow nanospray for the normalization of conventional liquid chromatography/mass spectrometry through equimolar response: standard-free quantitative estimation of metabolite levels in drug discovery.

Nanospray experiments were performed on an ensemble of drug molecules and their commonly known metabolites to compare performance with conventional electrospray ionization (ESI) and to evaluate equimolar response capabilities. Codeine, dextromethorphan, tolbutamide, phenobarbital, cocaine, and morphine were analyzed along with their well-known metabolites that were formed via hydroxylation, dealkylation, hydrolysis, and glucuronidation. Nanospray exhibited a distinct trend toward equimolar response when flow rate was reduced from 25 nL/min to less than 10 nL/min. A more uniform response between the parent drug and the corresponding metabolites was obtained at flow rates of 10 nL/min or lower. The largest discrepancy was within +/-50% for plasma samples. Nanospray was used as a calibrator for conventional ESI liquid chromatography/tandem mass spectrometry (LC/MS/MS) and normalization factors were applied to the quantitation of an acyl-glucuronide metabolite of a proprietary compound in rat plasma. A nanospray calibration method was developed with the standard curve of the parent drug to generate quantitative results for drug metabolites within +/-20% of that obtained with reference standards and conventional ESI. The nanospray method provides a practical solution for the quantitative estimation of drug metabolites in drug discovery when reference standards are not available.