Avnesh Kumari

Biodegradable polymeric nanoparticles based drug delivery systems

Biodegradable nanoparticles have been used frequently as drug delivery vehicles due to its grand bioavailability, better encapsulation, control release and less toxic properties. Various nanoparticulate systems, general synthesis and encapsulation process, control release and improvement of therapeutic value of nanoencapsulated drugs are covered in this review. We have highlighted the impact of nanoencapsulation of various disease related drugs on biodegradable nanoparticles such as PLGA, PLA, chitosan, gelatin, polycaprolactone and poly-alkyl-cyanoacrylates.

Development of biodegradable nanoparticles for delivery of quercetin.

The antioxidant molecule quercetin has been encapsulated on poly-D,L-lactide (PLA) nanoparticles by solvent evaporation method for the improvement of its poor aqueous solubility and stability. The surface morphology and average size of PLA and quercetin loaded PLA nanoparticles are 170+/-25 and 130+/-30 nm respectively. The antioxidant activities of the PLA encapsulated quercetin nanomedicine are identical to free quercetin. The nanoencapsulation efficiency of quercetin evaluated by HPLC and antioxidant assay is 96.7%. The in vitro release kinetics under physiological condition show initial burst release followed by slow and sustained release. The complete release and maximum retention of quercetin is 72 and 96h respectively. The less fluorescence quenching efficiency of quercetin-PLA nanoparticles than free quercetin on BSA confirms the controlled release of quercetin from PLA nanoparticles. These properties of PLA encapsulated quercetin molecule pave way for encapsulating various therapeutically less useful highly active antioxidant molecules towards the development of better therapeutic compounds.

Development of peptide and protein nanotherapeutics by nanoencapsulation and nanobioconjugation

The targeted delivery of therapeutic peptide by nanocarriers systems requires the knowledge of interactions of nanomaterials with the biological environment, peptide release, and stability of therapeutic peptides. Therapeutic application of nanoencapsulated peptides are increasing exponentially and >1000 peptides in nanoencapsulated form are in different clinical/trial phase. This review covers current scenario of therapeutic protein and peptides encapsulation on polymer to metallic nanocarriers including methods of protein encapsulation, peptide bioconjugation on nanoparticles, stability enhancement of encapsulated proteins and its biomedical applications.

Nanoencapsulation and characterization of Albizia chinensis isolated antioxidant quercitrin on PLA nanoparticles

The plant isolated antioxidant quercitrin has been encapsulated on poly-d,l-lactide (PLA) nanoparticles by solvent evaporation method to improve the solubility, permeability and stability of this molecule. The size of quercitrin-PLA nanoparticles is 250±68nm whereas that PLA nanoparticles is 195 ± 55nm. The encapsulation efficiency of nanoencapsulated quercitrin evaluated by HPLC and antioxidant assay is 40%. The in vitro release kinetics of quercitrin under physiological condition reveals initial burst release followed by sustained release. Less fluorescence quenching is observed with equimolar concentration of PLA encapsulated quercitrin than free quercitrin. The presence of quercitrin specific peaks on FTIR of five times washed quercitrin loaded PLA nanoparticles provides an extra evidence for the encapsulation of quercitrin into PLA nanoparticles. These properties of quercitrin nanomedicine provide a new potential for the use of such less useful highly active antioxidant molecule towards the development of better therapeutic for intestinal anti-inflammatory effect and nutraceutical compounds.

Cellular interactions of therapeutically delivered nanoparticles

Introduction: Nanoparticles (NPs) are used extensively in drug delivery. They are administered through various routes in the host, and their uptake by the cellular environment has been observed in several pathways. After uptake, NPs interact with cells to different extents, depending on their size, shape, surface properties, ligands tagged to the surface and tumor architecture. Complete understanding of such cellular uptake mechanisms and interactions of NPs is important for their effective use in drug delivery. Areas covered: This article describes the various cellular pathways for NP uptake, and the factors affecting NP uptake and interactions with cells. Understanding these two important aspects will help in the future design of NPs for effective and targeted drug delivery. Expert opinion: Surface charge and ligands tagged on the surface of NPs play a critical role in their uptake and interaction with cells; so surface modifications of NPs can offer increased drug delivery effectiveness, for example, the coupling of ligands on the surface of NPs can increase cellular binding, and NPs in biological fluids can be coated with proteins and as such can exert biological effects. All of the factors affecting NP uptake need to be investigated thoroughly before interpreting any NP–cellular interactions.

Evaluating the Toxicity of Selected Types of Nanochemicals

Nanotechnology is a fast growing field that provides for the development of materials that have new dimensions, novel properties, and a broader array of applications. Various scientific groups are keen about this technology and are devoting themselves to the development of more, new, and better nanomaterials. In the near future, expectations are that no field will be left untouched by the magical benefits available through application of nanotechnology. Presently, there is only limited knowledge concerning the toxicological effects of NPs. However, it is now known that the toxic behavior of NPs differ from their bulk counterparts. Even NPs that have the same chemical composition differ in their toxicological properties; the differences in toxicity depend upon size, shape, and surface covering. Hence, before NPs are commercially used it is most important that they be subjected to appropriate toxicity evaluation. Among the parameters of NPs that must be evaluated for their effect on toxicity are surface charges, types of coating material, and reactivity of NPs. In this article, we have reviewed the literature pertinent to the toxicity of metal oxide NPs, metallic NPs, quantum dots (QDs), silica (SiO2) NPs, carbon nanotubes (CNTs), and certain other carbon nanomaterials (NMs). These NPs have already found a wide range of applications around the world. In vitro and in vivo studies on NPs have revealed that most are toxic to animals. However, their toxic behavior varies with their size, shape, surface charge, type of coating material and reactivity. Dose, route of administration, and exposure are critical factors that affect the degree of toxicity produced by any particular type of NP. It is for this reason that we believe a careful and rigorous toxicity testing is necessary before any NP is declared to be safe for broad use. We also believe that an agreed upon testing system is needed that can be used to suitably, accurately, and economically assess the toxicity of NPs. NPs have produced an array of different toxic effects in many different types of in vivo and in vitro studies. The types of effects that NPs have produced are those on the pulmonary, cardiac, reproductive, renal and cutaneous systems, as well as on various cell lines. After exposures, significant accumulations of NPs have been found in the lungs, brain, liver, spleen, and bones of test species. It has been well established that the degree of toxicity produced by NPs is linked to their surface properties. Soluble NPs are rendered toxic because of their constituents; however, the situation is entirely different for insoluble NPs. Stable metal oxides do not show any toxicity, whereas metallic NPs that have redox potential may be cytotoxic and genotoxic. The available data on NP toxicity is unfortunately limited, and hence, does not allow scientists to yet make a significant quantitative risk assessment of the safety of synthesized NPs. In this review, we have endeavored to illustrate the importance of having and using results from existing nanotoxicological studies and for developing new and more useful future risk assessment systems. Increased efforts of both an individual and collective nature are required to explore the future pros and cons of nanotechnology.

Plant Extract Synthesized PLA Nanoparticles for Controlled and Sustained Release of Quercetin: A Green Approach

Background Green synthesis of metallic nanoparticles (NPs) has been extensively carried out by using plant extracts (PEs) which have property of stabilizers/ emulsifiers. To our knowledge, there is no comprehensive study on applying a green approach using PEs for fabrication of biodegradable PLA NPs. Conventional methods rely on molecules like polyvinyl alcohol, polyethylene glycol, D-alpha-tocopheryl poly(ethylene glycol 1000) succinate as stabilizers/emulsifiers for the synthesis of such biodegradable NPs which are known to be toxic. So, there is urgent need to look for stabilizers which are biogenic and non-toxic. The present study investigated use of PEs as stabilizers/emulsifiers for the fabrication of stable PLA NPs. Synthesized PLA NPs through this green process were explored for controlled release of the well known antioxidant molecule quercetin. Methodology/Principal Findings Stable PLA NPs were synthesized using leaf extracts of medicinally important plants like Syzygium cumini (1), Bauhinia variegata (2), Cedrus deodara (3), Lonicera japonica (4) and Eleaocarpus sphaericus (5). Small and uniformly distributed NPs in the size range 70±30 nm to 143±36 nm were formed with these PEs. To explore such NPs for drugs/ small molecules delivery, we have successfully encapsulated quercetin a lipophilic molecule on a most uniformly distributed PLA-4 NPs synthesized using Lonicera japonica leaf extract. Quercetin loaded PLA-4 NPs were observed for slow and sustained release of quercetin molecule. Conclusions This green approach based on PEs mediated synthesis of stable PLA NPs pave the way for encapsulating drug/small molecules, nutraceuticals and other bioactive ingredients for safer cellular uptake, biodistribution and targeted delivery. Hence, such PEs synthesized PLA NPs would be useful to enhance the therapeutic efficacy of encapsulated small molecules/drugs. Furthermore, different types of plants can be explored for the synthesis of PLA as well as other polymeric NPs of smaller size.

Nanotechnology in Agri-Food Sector

The emergence of nanotechnology developments using nanodevices/nanomaterials opens up potential novel applications in agriculture and food sector. Smart delivery systems, biosensors, and nanoarrays are being designed to solve the problems faced in agriculture sector. Similarly, food sector is also benefited through the use of smart biosensors, packaging materials, and nanonutraceuticals. Despite the great potential of nanotechnology in agri-food sector, people are ambiguous about use in food applications because of suspected potential health risks and environmental concerns. Nanoparticles, due to their unique characteristics, including small size, shape, high surface area, charge, chemical properties, solubility and degree of agglomeration can cross cell boundaries or pass directly from the lungs into the blood stream and ultimately reach to all of the organs in the body. This is the reason why they may pose higher risk than the same mass and material of larger particles. In this paper, we have made an attempt to give an overview of nanotechnology developments in agri-food sector, risks associated with nanomaterials and toxicity regulations for policy framework.

Nanoencapsulation for drug delivery

Nanoencapsulation of drug/small molecules in nanocarriers (NCs) is a very promising approach for development of nanomedicine. Modern drug encapsulation methods allow efficient loading of drug molecules inside the NCs thereby reducing systemic toxicity associated with drugs. Targeting of NCs can enhance the accumulation of nanonencapsulated drug at the diseased site. This article focussed on the synthesis methods, drug loading, drug release mechanism and cellular response of nanoencapsulated drugs on liposomes, micelles, carbon nanotubes, dendrimers, and magnetic NCs. Also the uses of these various NCs have been highlighted in the field of nanotechnology.

Encapsulation of podophyllotoxin and etoposide in biodegradable poly-d,l-lactide nanoparticles improved their anticancer activity

Abstract To improve the efficacy podophyllotoxin (PODO) and etoposide (ETOPO) were encapsulated in poly-d,l-lactide nanoparticles (PLA NPs). The size of synthesised PODO-loaded PLA NPs and ETOPO-loaded PLA NPs was 100 ± 17 nm and 163 ± 20 nm and their encapsulation efficiency was 17 and 48%, respectively. In vitro release studies showed initial burst release followed by slow and sustained release. In vitro cytotoxicity of synthesised NPs was assessed using A549 and CHO-K1 cells. Blank PLA NPs did not show any toxicity. While PODO-loaded PLA NPs showed higher in vitro cytotoxicity in comparison to ETOPO-loaded PLA NPs against both cell lines. Also, the cytotoxicity of both PODO-loaded PLA NPs and ETOPO-loaded PLA NPs was higher compared to pure drugs. Hence, this study documents the improvement in efficacy of these molecules upon encapsulation in PLA NPs and could be an important strategy for better therapeutics.