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Cancer being one of the most precarious and second most fatal diseases evokes opportunities for multimodal delivery platforms which will act synergistically for efficient cancer treatment. Multifunctional iron oxide magnetic nanoparticles (IONPs) are being studied for few decades and still attracting increasing attention for several biomedical applications owing to their multifunctional design and intrinsic magnetic properties that provide a multimodal theranostic platform for cancer therapy, monitoring and diagnosis. The review article aims to provide brief information on various surface chemistries involved in modulating IONPs properties to exhibit potential therapy in cancer treatment. The review addresses structural, magnetic, thermal and optical properties of IONPs which aids in the fabrication of efficient multimodal nanoplatform in cancer therapy. The review discussed the pharmacokinetics of IONPs and attributes influencing them. This review inculcates recent advancements in therapies, focused on tumor-microenvironment-responsive and targeted therapy along with their eminent role in cancer diagnosis. The concept of stimuli-responsive including endogenous, exogenous and dual/multi stimuli-based delivery platform demonstrated significantly enhanced anticancer therapy. Several therapeutic approaches viz. chemotherapy, radiotherapy, immunotherapy, hyperthermia, gene therapy, sonodynamic therapy, photothermal, photodynamic-based therapy along with biosensing and several toxicity aspects of IONPs have been addressed in this review for effective cancer treatment.

Although extensive research is being done to combat SARS-CoV-2, we are yet far away from a robust conclusion or strategy. With an increased amount of vaccine research, nanotechnology has found its way into vaccine technology. Researchers have explored the use of various nanostructures for delivering the vaccines for enhanced efficacy. Apart from acting as delivery platforms, multiple studies have shown the application of inorganic nanoparticles in suppressing the growth as well as transmission of the virus. The present review gives a detailed description of various inorganic nanomaterials which are being explored for combating SARS-CoV-2 along with their role in suppressing the transmission of the virus either through air or by contact with inanimate surfaces. The review further discusses the use of nanoparticles for development of an antiviral coating that may decrease adhesion of SARS-CoV-2. A separate section has been included describing the role of nanostructures in biosensing and diagnosis of SARS-CoV-2. The role of nanotechnology in providing an alternative therapeutic platform along with the role of radionuclides in SARS-CoV-2 has been described briefly. Based on ongoing research and commercialization of this nanoplatform for a viral disease, the nanomaterials show the potential in therapy, biosensing, and diagnosis of SARS-CoV-2.

The unique physical and chemical properties of monometallic nanoparticles have been comprehensively explored. Analogously, the combination of two metals induces alterations in the system’s electron density, termed as Bimetallic nanoparticles (BMNP’s) were found to be more desirable than monometallic nanoparticles due to improved stability, activity, and selectivity, thus altering the chemical, optical, and electrical properties. In this review, we showcase the importance in the context of biomedical applications. The article sheds light on utilising BMNP’s in the field of theranostics, diagnosis, and therapeutics by focusing on anticancer, antimicrobial and wound healing activity along with the toxicological problems associated with BMNP’s. In conclusion, BMNP’s can be used as a novel therapeutic and diagnostic system to tackle major health concerns.

With growing interest in polymers of natural origin, innumerable polysaccharides have gained attention for their biomedical application. Pullulan, one of the FDA approved nutraceuticals, possesses multiple unique properties which make them highly advantageous for biomedical applications. This present review encompasses the sources, production, properties and applications of pullulan. It highlights various pullulan based stimuli-responsive systems (temperature, pH, ultrasound, magnetic), subcellular targeted systems (mitochondria, Golgi apparatus/endoplasmic reticulum, lysosome, endosome), lipid-vesicular systems (solid-lipid nanoparticles, liposomes), polymeric nanofibres, micelles, inorganic (SPIONs, gold and silver nanoparticles), carbon-based nanoplatforms (carbon nanotubes, fullerenes, nanodiamonds) and quantum dots. This article also gives insight into different biomedical, therapeutic and diagnostic applications of pullulan viz., imaging, tumor targeting, stem cell therapy, gene therapy, vaccine delivery, cosmetic applications, protein delivery, tissue engineering, photodynamic therapy and chaperone-like activities. The review also includes the toxicological profile of pullulan which is helpful for the development of suitable delivery systems for clinical applications.

The present review deals in-depth with the current application of nanotechnology in targeting the major pathological hallmarks of Alzheimer's disease. This review further focuses on the surface modification of the nanocarriers using antibody, aptamers, proteins and peptides for specific targeting in the brain by overcoming the biological barriers such as blood brain barrier. The stimuli responsive/pulsatile drug delivery nanoplatforms using stimuli such as pH, temperature, photo-thermal, reactive oxygen species, ultrasonic stimulation and electrical stimulation, which help to create a micro-environment to either trigger the site-specific drug release from the nanoplatform or to reduce the disease burden in the brain, have been discussed. The targeting of nanoplatforms to sub-cellular compartments such as mitochondria, nuclei, endoplasmic reticulum, golgi apparatus and lysosomes along with receptor specific interactions such as such folate, lactoferrin, transferrin, insulin and low-density lipoprotein (LDL) receptors has been included to give reader an idea about strategies to enhance cellular co-localization and receptor based targeting of nanoparticles to enhance efficacy of delivery platform. This article describes the various type of nanoplatforms which include lipidic nanoplatforms, polymeric nanoplatforms, inorganic nanoplatforms (metallic nanocarriers, quantum dots, ceramic based nanocarriers), carbon based nanocarriers and cell derived or biomimetic (exosomes and virus based) nanoplatforms, to either deliver the active ingredient or to themselves target the Alzheimer's disease pathology. Thus the review gives a detailed insight of all the recent research studies carried out using nanotechnology in the field of Alzheimer's disease.

A stability-indicating reversed-phase high-performance liquid chromatography method for simultaneous estimation of dolutegravir sodium and lamivudine encapsulated in the nanoliposomal formulation was developed. The chromatographic parameters namely, organic phase ratio, flow rate, and sample injection volume were selected as independent factors and were optimized by multivariate Box-Behnken design. Responses analyzed were retention time, peak area, and resolution. The optimized chromatographic method with Hypersil BDS C8 CN column as stationary phase and methanol and acetonitrile mixture and acidified Milli-Q water (pH 2.8, adjusted with 0.02% v/v orthophosphoric acid) as the mobile phase in an isocratic elution mode was validated according to parameters of International Conference on Harmonization Q1(R2) guidelines. The validated reversed-phase high-performance liquid chromatography method exhibited specificity for both dolutegravir sodium and lamivudine in the presence of degradation products as well as the liposomal matrix. This method was effectively utilized to determine the amount of drug entrapped and drug loading efficiency of dolutegravir sodium and lamivudine in a nano-liposomal formulation.

This review focuses on the various formulation approaches that have been explored to achieve localized delivery in breast cancer. The rationale behind the necessity of localized drug delivery has been extensively reviewed. The review also emphasizes the various possible routes for achieving localized drug delivery. Particularly, different types of nanoplatforms like lipid-based drug carriers, polymeric particles, hydrogels, drug conjugates and other formulation strategies like microneedles and drug-eluting implants, which have been used to increase tumor retention and subsequently halt tumor progression, have been deliberated here. In addition, the significant challenges that may be encountered in the delivery of anticancer drugs and the aspects that require careful evaluation for effective localized delivery of chemotherapeutic agents have been discussed.

In the present investigation, FePt alloy nanoparticles were synthesized with controlled size and elemental composition followed by surface modification using (3-Aminopropyl) triethoxysilane (APTES). Lenalidomide was covalently bound to FePt-NH2 by pH sensitive hydrazone bonding. Hyaluronic acid was conjugated to amino groups of APTES while lactoferrin (Lf) was directly conjugated to excess carboxylic group present on hyaluronic acid (HA) to form surface modified pH sensitive alloy-drug nanoconjugates (SPANs). The multifunctional nanoconjugates were characterized and evaluated using extensive in vitro and in vivo techniques. The nanoconjugates demonstrated excellent heating ability on exposure to alternating magnetic field and near-infrared laser irradiation. The acidic microenvironment of lysozome triggered release of LND from SPANs. Owing to leaching of Fe and Pt contents, SPANs demonstrated ability to generate reactive oxygen species (ROS) in U87MG cell line which further enhanced therapeutic effect of SPANs. Significant difference in cell viability suppression was observed in in vitro photothermal, chemo-photothermal and chemo-magnetophotothermal killing of cancer cells using SPANs in U87MG cell lines. Significant difference in heating ability and cell cytotoxicity of SPANs in comparison to alternative magnetic field and NIR irradiation was observed for DUAL-mode exposure of SPANs. The results of cellular internalization study showed efficient internalization of SPANs inside U87MG cells. The in vivo results (both qualitative and quantitative) confirmed enhanced uptake of SPANs in brain after intranasal administration with enhanced nasal and mucus penetration owing to presence of Lf. No significant interaction was observed with ECM and mucin due to presence of carboxyl group on SPANs.

In the present study, we have developed the core-shell metal organic framework (MOF) of zinc, wherein titanocene dichloride (TC) loaded lactoferrin (Lf) functioned as a core. The complexation of TC to Lf was studies using molecular dynamics study, Quantum mechanical model and spectroscopic investigations. Plackett-Burman design was used to screen and select the critical factors affecting the responses (size, zeta potential and PDI) while the effect of those parameter on the quality attributes (size and yield) was studied by means of a Box-Behnken design. The optimised Lf-TC nanoparticles were loaded inside the ZIF-8 framework along with an anticancer agent 5 Fluorouracil and characterized using techniques like FTIR, PXRD, Raman spectroscopy, EDX and UV-NIR spectroscopy and morphological techniques like SEM, TEM, AFM. The compatibility of the loaded ZIF-8 framework was examined by haemocompatibility studies. The potential of developed nanoplatform against Neuroblastoma was assessed using a cell line studies along with in vivo toxicity studies to ascertain its safety for after in-vivo administration in Wistar rats. Therefore, we can conclude that by employing the approach of DOE we were able to optimize the size and yield of Lf-TC NPs and further by loading inside ZIF-8 framework along with an anticancer drug like 5 fluorouracil we were able to develop a potential nanoplatform for the multimodal therapy of Neuroblastoma.

With the changing face of healthcare, there is a demand for drug delivery systems that have increased efficacy and biocompatibility. Nanotechnology derived drug carrier systems were found to be ideal candidates to meet these demands. Among the vast number of nanosized delivery systems, biomimetic nanoparticles have been researched at length. These nanoparticles mimic cellular functions and are highly biocompatible. They are also able to avoid clearance by the reticuloendothelial system which increases the time spent by them in the systemic circulation. Additionally, their low immunogenicity and targeting ability increase their significance as drug carriers. Based on their core material we have summarized them as biomimetic inorganic nanoparticles, biomimetic polymeric nanoparticles, and biomimetic lipid nanoparticles. The core then may be coated using membranes derived from erythrocytes, cancer cells, leukocytes, stem cells, and other membranes to endow them with biomimetic properties. They can be used for personalized therapy and diagnosis of a large number of diseases, primarily cancer. This review summarizes the various therapeutic approaches using biomimetic nanoparticles along with their applications in the field of cancer imaging, nucleic acid therapy and theranostic properties. A brief overview about toxicity concerns related to these nanoconstructs has been added to provide knowledge about biocompatibility of such nanoparticles.

Nano-Bio interface involves the dynamic interactions of nanomaterial and a living system. Association of nanotechnology and biology has been a valuable tool in improving the potentials of biomedical research. Exquisite structures of nanoparticles comparable in size with biomolecules and the unique possibility of tuning their chemical and physical functionality at small length scales make them more attractive for biological research. In this review, we comprehend Nano-Bio interactions at cellular levels and discuss parameters involved in determining nano-bio interactions. Techniques used for the characterization of nano-bio interactions have also been discussed. Applications of nanotechnology as a tool for manipulating cellular behaviors, studying important biological processes such as adhesion, morphology, and proliferation, and nanoparticles as nanoprobes and nanosensors have been discussed here. Knowledge of these interactions and processes at a cellular level will be useful for understanding the bioenergetics of subcellular organelle and might provide innovative ideas for designing new tools to enhance the understanding of cellular functions. Further, detailed information about the cellular and subcellular processes will be rather helpful in designing new nanocarriers and drug discovery.

Gout is the world's most popular inflammatory arthritis and the prevalence of gout is rapidly rising worldwide. Typically, gout develops in a single joint as excessive swelling and intense pain wherein excessive deposition of uric acid (UA) crystals results in inflammation of the joint. Accordingly, UA is considered an effective biomarker to diagnose gout. Recently, the use of innovative sensors has attracted great attention, as it is effortless, responsive, quick, and powerful. While the traditional sensors for UA assessment are widely used, they pose many limitations and hurdles in terms of sensitivity, selectivity, and simplicity. In this vein, metal ions and organic ligand-based metal–organic framework (MOF) have gained much attention for the recognition of UA due to its larger surface area, porosity, high sensitivity, and defined selectivity. In this review, we provide details on the latest developments of MOF-centered biosensors for sensitive detection of UA. The status of gout, fundamentals of MOF, and MOF availed for detection of UA have been elaborated. Besides, we highlighted the nanoparticles and conjugates that rely on advanced strategies along with MOF that boost the sensitivity and selectivity towards the UA. Interestingly, different surface architectured MOFs biosensors showed a lower detection limit for UA from μM to nM. Finally, the threats and potential opportunities for MOF-based UA biosensors have been summarized. Therefore, based on ongoing research, the commercialization of this advanced platform for the biosensing of diverse biomarkers will open a new door for the in vitro diagnosis of assorted diseases.

Dendrimers are globular three-dimensional synthetic macromolecules that are highly branched with a definite molecular weight. The distinct physicochemical properties and advancements in the synthesis of a variety of biodegradable dendritic scaffolds were studied in several biomedical applications, primarily for the delivery of drug and protein to targeted sites. However, in the context of oral delivery, the knowledge of pharmacokinetics of the dendrimer and its interaction with cellular components is obscure, and therefore further studies will uplift/elevate the effective clinical translation potential of dendrimers. In this review, we showcase the unique tuneable physicochemical properties of dendrimers alongside the advanced synthetic routes and diverse classes of dendritic scaffolds. In particular, the interaction of dendrimer with biological fluids, cellular uptake, toxicity, and degradation mechanisms are also discussed considering oral delivery/application. We focused exclusively on the influence of dendrimer surface groups and their charge, core chemistry, combination with oral permeation enhancers, effect of lipidation as well as dendrimer conjugation with other nanocarriers as an attempt to improve the therapeutic efficacy of drugs via the oral route. Majority of studies utilize Polyamidoamine (PAMAM) dendrimer to improve the oral bioavailability of drugs; however, toxicity limits its application. Therefore, exploring other classes of dendrimers along with the use of self-assembling dendrimers has been discussed in recent advancements and future perspectives for successful clinical translation of dendrimers in oral delivery.

The present investigation deals with successful synthesis and surface functionalisation of mesoporous alumina (MeAl) nanoparticles by simplified sol–gel method using cetyl trimethyl ammonium bromide (CTAB) and pluronic as a template. Surface functionalisation of MeAl was performed to determine the selectivity of surface groups for coupling with model drug molecule. Repaglinide a BCS class II drug was loaded as a model drug on synthesised MeAl nanoparticle and studied for its sustained release capability. The synthesised and repaglinide loaded MeAl nanoparticles were characterised by Fourier transform infrared Spectroscopy, X‐ray diffraction, field emission scanning electron microscopy with EDAX, Transmission electron microscopy and differential scanning calorimetric. Results from the dissolution study confirmed the sustained release behaviour of the nanparticles which was up to 24 h. The cell viability assay demonstrated that 0.2 to 1 mg/ml concentration of MeAl was significantly less cytotoxic to the Chinese Hamster Ovary (CHO) cells. The authors’ experimental studies suggest that MeAl can be used as drug carrier and have a potential to increase the stability, loading efficiency and patient compliance for poorly water‐soluble drugs such as repaglinide.

Hydrophobic modification of low molecular weight polyethylenimine (PEI 2 kDa) by cholic acid (ChA) was done to obtain PEI2-ChA. The nanoplexes of PEI2-ChA with gWIZ-GFP demonstrated increase transfection efficiency (∼27%) in NT8e cell lines. The cell-cycle analysis of NT8e cells (p53 mutant) treated with transferrin containing nanoplexes showed increased apoptosis of cells. In vitro protein expression revealed expression of exogenous p53 protein. In vivo imaging of mice showed localized signal for GFP protein in brain region. The tumors of mice treated with transferrin containing nanoplexes of PEI2-ChA were ∼5 times smaller in size than the tumor of untreated animals.

Present investigation deals with, tacrolimus eluting, self-expandable, biodegradable stent fabricated by solvent casting method. The design was based on shape memory polymers, which possess the ability to memorize temporary shape that can substantially differ from their initial permanent shape. A set of biodegradable polymers blend was used such as poly-lactic acid (PLA) and poly-l-glycolic acid (PLGA) to study the shape memory effect of polymer. The prepared stent was assessed for various parameters like Scanning Electron Microscopy (SEM), In-vitro and Ex vivo expansion, Drug content, In-vitro drug release, Haemocompatibility, Differential Scanning Calorimetry (DSC), Fourier Transform Infrared spectroscopy (FTIR), and Textural Characterization.

The present investigation deals with synthesis of graphene oxide (GO) and fabrication of GO-based hybrid nanocomposites (Ncs). Synthesized GO and Ncs were primarily confirmed by UV visible and Fourier transform infrared (FT-IR) spectroscopy. Fabricated Ncs showed potential antimicrobial activity against Gram-positive and Gram-negative bacterial strains. Surface morphology, Elemental analysis, and FTIR imaging analysis were carried out to confirm Ncs formation. The Ncs were impregnated into the pullulan polymeric layer-by-layer (LbL) ultrathin film by using novel spin-coating approach. Mechanical properties were determined using Brookfield texture analyzer, and percentage moisture content confirmed the physicochemical stability of LbL film.

Polyethylenimine (PEI) has recently been widely studied for the design of nucleic acid delivery vehicles. Gene delivery using PEI involves condensation of DNA into compact particles, uptake into the cells, release from the endosomal compartment into the cytoplasm, and uptake of the DNA into the nucleus. PEIs being positively charged, linear or branched polymers are able to form nanoscale complexes with small RNAs, leading to RNA protection, cellular delivery, and intracellular release. This review highlights the important properties of various PEIs with regard to their use for nucleic acid delivery. Brief discussion on cellular uptake mechanism of non-viral vector is included to understand its utility for gene delivery. Applications of modified PEI for increased efficacy, altered pharmacokinetic properties; improved biocompatibility and targeted delivery have also been discussed. An overview of simulation studies which can help in understanding the underlying complexation mechanism has also been included. The review provides a brief discussion about clinical trials and patents related to nucleic acid delivery using PEI based systems.

Liquid metals in recent years have grabbed the attention of researchers due to their expanded applicability not only in the field of therapeutics but also in theranostic. Acknowledged as a nuclear medicine due to its radioactivity, Gallium finds its widespread application in disorders of bone, calcium metabolism, and cancer. The present article deals with the advancement of gallium based nanoplatforms for therapy, imaging, and biosensing of cancers. The article describes the gallium based nanoconjugates and furnishes one's understanding of various therapeutic approaches such as photothermal therapy, sonodynamic therapy, radiotherapy, and immunotherapy along with various imaging platforms and biosensing platforms. A brief section related to patents on gallium based nanoplatforms in cancer has been included along with various molecular docking and simulation studies done on gallium. The recent advancement with respect to drug delivery gives an insight into the future perspective of gallium based nanoplatforms in the field of cancer theranostic.

In the present investigation, one-pot synthesis method has been reported for the preparation of tramadol loaded proliposomes (PLs) coated with chitosan (CCPLs) and carboxymethyl chitosan (CM-ChPLs) for intranasal administration. Spray drying method used for formulation of PLs was optimized using Design of Experiment (DoE). The formulated PLs were extensively characterized and evaluated. The formulation was assessed for biocompatibility using cell viability assay, along with estimation of inflammatory potential of PLs, in vitro drug permeation across nasal mucosa, in vitro mucoadhesion study, nasal mucosa penetration study and analysis of powder spray pattern. The prepared PLs were also assessed for their interactions and stability under various physiological conditions. The interaction of different PLs with serum protein and mucin was assessed using DLS and zeta potential measurement. The stability study demonstrated superiority of coated PLs over uncoated PLs. The cell viability study confirmed the biocompatibility of developed PLs while confocal microscopy confirmed enhanced permeation of coated PLs across nasal mucosa. All PLs were stable in simulated nasal fluid. The in vitro drug release studies demonstrated sustained release which was also supported by results obtained after ex vivo permeation study. The overall results confirmed that type of surface modification and surface charge along with particle size plays an important role in type and extent of interaction of PLs with proteins and mucin. This could directly or indirectly affect the diffusion or penetration of nanoliposomes across mucosa and ultimately affects in vivo results.

The current review focuses towards the advancements made in the past decade in the field of nanotechnology for the early Alzheimer’s disease (AD) diagnosis. This review includes the application of nanomaterials and nanosensors for the early detection of the main AD biomarkers (amyloid beta, phosphorylated tau, apolipoprotein E4 allele or APOE4, microRNAs, cholesterol, hydrogen peroxide etc) in biological fluids, to detect the biomarkers at a very low concentration ranging in pico, femto and even atto molar concentrations. The field of drug development has always aimed and is constantly working on developing disease modifying drugs, but these drugs will only succeed when given in the early disease stages. Thus, developing efficient diagnostic tools is of vital importance. Various nanomaterials such as liposomes; dendrimers; polymeric nanoparticles; coordination polymers; inorganic nanoparticles such as silica, manganese oxide, zinc oxide, iron oxide, super paramagnetic iron oxides; quantum dots, silver nanoparticles, gold nanoparticles, and carbon based nanostructures (carbon nanotubes, graphene oxide, nanofibres, nanodiamonds, carbon dots); Up-conversion nanoparticles; 2D nanomaterials; and radioactive nanoprobes have been used in constructing and improving efficiency of nano-sensors for AD biosensing at an early stage of diagnosis.

The present work deals with the design and process optimization for preparation of lactoferrin nanoparticles as carrier for delivery of curcumin (CLf-NPs) using quality by design (QbD) approach. Desolvation technique was selected for preparation of Lf-NPs. The concept of QbD was followed in stepwise manner including risk analysis FMEA methodology. Plackett-Burman screening design employing eight factors and two levels was selected for screening study and custom design was selected for further analysis. Curcumin was used as model polyphenol for assessing the encapsulating efficiency of Lf-NPs.

Delivery of drugs to the brain via nasal route has been studied by many researchers. However, low residence time, mucociliary clearance and enzymatically active environment of nasal cavity pose many challenges to successful nasal delivery of drugs. We aim to deliver methotrexate by designing thermosensitive nanodispersion exhibiting enhanced residence time in nasal cavity and bypassing the blood brain barrier (BBB). PLA nanoparticles were developed using solvent evaporation technique. The developed nanoparticles were further dispersed in prepared thermosensitive vehicle of poloxamer 188 and Carbopol 934 to impart the property of increased residence time. The formulated nanoparticles demonstrated no interaction with the simulated nasal fluids (SNF), mucin, serum proteins and erythrocytes which demonstrate the safety of developed formulation for nasal administration. The penetration property of nanoparticles though the nasal mucosa was higher than the pure drug due to low mucociliary clearance. The developed nanoparticles diffused though the membrane pores and rapidly distributed into the brain portions compared to the pure drug. There was detectable and quantifiable amount of drug seen in the brain as demonstrated by in vivo brain distribution studies with considerably low amount of drug deposition in the lungs. The pharmacokinetic parameters demonstrated the enhancement in circulation half life, area under curve (AUC) and Cmax of the drug when administered intranasal in encapsulated form. Thus, the thermosensitive nanodispersions are surely promising delivery systems for delivering anticancer agents though the nasal route for potential treatment of brain tumors.

Multimodal therapeutic approach has been gaining lot of attention for effective therapy of cancer. In the present work, a novel and unique pH responsive nanoplatform have been developed for multimodal therapy of glioblastoma using protein, biopolymer and MOFs. Lactoferrin (Lf) has been used as protein matrix for loading titanocene which was then enclosed in ZIF-8 framework along with 5-FU (ZIF-8@Lf-TC). The ZIF-8 was further coated with Lenalidomide-HA conjugate linked via hydrazone linkage (LND-HA@ZIF-8@Lf-TC). The developed nanocomposite was extensively characterized using spectroscopic, x-ray and electron microscopic techniques. The nanocomposites were evaluated for pH responsive drug release, stability, bio-interaction, and haemocompatibility which confirmed pH responsive nature of nanocomposite, stability and absence of any significant interaction with biomolecules. In obtained results for in vitro cell line studies performed in U87MG and RAW264.7 cells demonstrated enhanced cell cytotoxicity against cancer cells which was further supported by results of cellular ROS generation and surface ROS generation by nanocomposites. The Zinc and Lf mediated disruption of intracellular IL-6 and TNFα levels was observed with synthesized nanocomposites. They demonstrated pH responsive release of 5-FU and LND along with sustained release of both drugs in simulated medium. The LND-HA@ZIF-8@Lf-TC demonstrated superior cell growth supressing ability compared to ZIF-8@Lf-TC and ZIF-8. The nanocomposites were stable in biomimicking environment as well as did not show any significant interaction with RBC, plasma or CSF. The overall results suggest that LND-HA@ZIF-8@Lf-TC can be explored as promising platform for dual drug delivery mediated multimodal therapy of cancer.

Inorganic materials have lot of attention owing to their unique properties which can be explored for multiple biomedical application. Recently, alloy nanoparticles have been shown as potential candidate for multimodal therapy and imaging of cancer. In the present study, a novel pH responsive poly-l-lysine coated Fe3O4@FePt core shell nanoparticles have been developed for mitochondria targeted (Mito-PANPs) therapy of glioblastoma. The surface of synthesized nanoparticles was modified with mitochondria directing triphenylphsphonium ion (TPP) and hypoxic cancer cell directing protein chlorotoxin (CTX). An attempt has been made to provide multimodal therapy of GBM by targeting hypoxic tissue in combination with chemotherapeutic agent and chemo-photothermal therapy. The synthesized nanoconjugates were extensively characterized and evaluated. The obtained results demonstrated enhanced localization of mitochondria both in vitro and in vivo. A superior proliferation suppressing ability was observed via multiple molecular mechanism involving disruption in mitochondrial energetics. Considering the mitochondria targeting ability, along with specificity for glioma cells and hypoxic region of glioma, multimodal therapeutic approach (chemotherapy, ROS generation by Fe, photothermal therapy, radiotherapy and DNA strand breakage by Pt) and pH responsive drug release, Mito-PANPs can prove to be a promising nanotheranostic platform for tumor imaging and therapy with externally guided monitoring.

Brahmanand Dube,1,2 Abhijeet Pandey,1 Ganesh Joshi,3 Rita Mulherkar,3 Krutika Sawant1 1Pharmacy Department, Faculty of Pharmacy, The Maharaja Sayajirao University of Baroda, Vadodara, 2Wockhardt Research Centre, Wockhardt Ltd, Aurangabad, India; 3Genetic Engineering Laboratory, ACTREC Tata Memorial Centre, Kharghar, Navi Mumbai Abstract: Low-molecular-weight polyethylenimine has lower cytotoxicity than high molecular weight polyethylenimine, but it is not an efficient transfection agent because of limitations of DNA delivery into the cytoplasm. Therefore, in the present study, the hydrophobic modification of low-molecular-weight polyethylenimine (PEI 2kDa [PEI2]) by cholic acid (ChA) was performed to form PEI2-ChA, and in vitro and in vivo studies were performed. Results indicate that the nanoplexes of PEI2-ChA with gWIZ-GFP have greater transfection efficiency (27%) in NT8e cell lines as evaluated by flow cytometry and also observed by fluorescence imaging. The present study concluded that the transferrin-containing nanoplexes of PEI2-ChA conjugates with plasmid p53 warrant clinical trials in humans after exhaustive animal studies for use as a novel gene delivery system. Keywords: polyethylenimine, biodistribution, tumor regression

In the present investigation, a Quality by Design strategy was applied for formulation and optimization of aripiprazole (APZ) loaded PCL nanoparticles (APNPs) using nanoprecipitation method keeping entrapment efficiency (%EE) and particle size (PS) as critical quality attributes. Establishment of design space was done followed by analysis of its robustness and sensitivity. Characterization of optimized APNPs was done using DSC, FT-IR, PXRD and TEM studies and was evaluated for drug release, hemocompatibility and nasal toxicity. PS, zeta potential and %EE of optimized APNPs were found to be 199.2 ± 5.65 nm, − 21.4 ± 4.6 mV and 69.2 ± 2.34% respectively. In vitro release study showed 90 ± 2.69% drug release after 8 h. Nasal toxicity study indicated safety of developed formulation for intranasal administration. APNPs administered via intranasal route facilitated the brain distribution of APZ incorporated with the AUC0 → 8 in rat brain approximately 2 times higher than that of APNPs administered via intravenous route. Increase in Cmax was observed which might help in dose reduction along with reduction in dose related side effects. The results of the study indicate that intranasally administered APZ loaded PCL NPs can potentially transport APZ via nose to brain and can serve as a non-invasive alternative for the delivery of APZ to brain.