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Rutin (RUT) is a flavonoid obtained from a natural source and is reported for antithrombotic potential, but its delivery remains challenging because of its poor solubility and bioavailability. In this research, we have fabricated novel rutin loaded liposomes (RUT-LIPO, nontargeted), liposomes conjugated with RGD peptide (RGD-RUT-LIPO, targeted), and abciximab (ABX-RUT-LIPO, targeted) by ethanol injection method. The particle size, ζ potential, and morphology of prepared liposomes were analyzed by using DLS, SEM, and TEM techniques. The conjugation of targeting moiety on the surface of targeted liposomes was confirmed by XPS analysis and Bradford assay.

Background: Reflex cardio-vascular and respiratory (CVR) alterations evoked by intra-arterial instillation of nociceptive agents are termed vasosensory reflexes. Such responses elicited by optimal doses of inflammatory mediators have been described in our earlier work. Objective: The present study was designed to evaluate the interactions between subthreshold doses of inflammatory mediators on perivascular nociceptive afferents in urethane anesthetized rats. objective: The present study was designed to evaluate the interactions between sub-threshold doses of inflammatory mediators on the perivascular nociceptive afferents, in urethane anesthetized rats. Methods: Healthy male adult rats (Charles-Foster strain) were anesthetized with an intraperitoneal injection of urethane. After anesthesia, the right femoral artery was cannulated. Respiratory movements, blood pressure, and electrocardiogram were recorded. The interactions between subthreshold doses of algogens in the elicitation of vasosensory reflex responses were studied by instillation of bradykinin (1 nM) and histamine (100 µM) into the femoral artery one after the other, in either temporal combination in separate groups of rats. The CVR responses obtained in these groups were then compared with the responses produced by 100 µM histamine and 1 nM bradykinin in saline-pretreated groups, which served as control. Results: Subthreshold doses of histamine elicited transient tachypnoeic, hyperventilatory, hypotensive, and bradycardiac responses, in rats pretreated with subthreshold doses of bradykinin [P 0.05, two-sided Dunnett’s test]. Similar responses were elicited by bradykinin after histamine pretreatment compared to the saline-pretreated group. Furthermore, CVR responses produced by histamine in the bradykinin-pretreated group were greater in magnitude as compared to bradykinin-induced responses in the histamine-pretreated group [P Conclusion: The present study demonstrates that both bradykinin and histamine potentiate one another in the elicitation of vasosensory reflex responses, and bradykinin is a better potentiator than histamine at the level of perivascular nociceptive afferents in producing reflex CVR changes. conclusion: The present study demonstrates that both bradykinin and histamine potentiate one another in elicitation of vasosensory reflex responses and bradykinin is a better potentiator than histamine at the level of perivascular nociceptive afferents in producing reflex CVR changes.

COVID-19 is an infectious and highly contagious disease caused by SARS-CoV-2. The immunotherapy strategy has a great potential to develop a permanent cure against COVID-19. Innate immune cells are in constant motion to scan molecular alteration to cells led by microbial infections throughout the body and helps in clearing invading viruses. Harnessing immunological targets for removing viral infection, generally based on the principle of enhancing the T-cell and protective immune responses. Currently-approved COVID-19 vaccines are mRNA encapsulated in liposomes that stimulate the host immune system to produce antibodies. Given the vital role of innate immunity, harnessing these immune responses opens up new hope for the generation of long-lasting and protective immunity against COVID-19.

Cancer is the leading cause of mortality worldwide. Among all cancer types, lung cancer is recognized as the most lethal and highly metastatic. The application of targeted nanomedicine loaded with anticancer drugs is highly desirable for successful lung cancer treatment. However, due to the heterogenicity and complexity of lung cancer, the therapeutic effectiveness of a single receptor targeting nanomedicine is unfortunately limited. Therefore, the concept of dual-receptor-targeted nanomedicine is an emerging trend for the advancement in lung cancer therapeutics. In this review, the authors discuss various single- and dual-receptor-targeted nanomedicines that have been developed for lung cancer treatment. Furthermore, the authors also discussed all the types of receptors that can be utilized in combination for the development of dual-receptor-targeted nanomedicines.Globally, cancer is one of the leading causes of death. Among various cancers, lung cancer is highly lethal and quickly spreads to other body parts. Directly delivering the drugs to cancer cells has been possible due to the application of receptor-based targeted nanomedicine. However, variation among patients and the complexity of the lung cancer has depicted that a single-receptor-based drug targeting lung cancer has limited outcomes. Therefore, delivering the drug to the lungs via dual-receptor-targeted nanomedicine has added advantages over conventional and single-receptor-targeted drug-delivery systems. Hence, the authors have reviewed various single- and dual-receptor-targeted nanomedicines reported for lung cancer treatment.

Cabazitaxel (CZT) loaded chitosan-alginate based (CSA) nanoparticles were developed with dual targeting functions of both folate receptor and epidermal growth factor receptor (EGFR) using ionic gelation technique. The chitosan-folate conjugate was synthesized, and characterized by using FTIR, NMR and Mass spectroscopy. The physicochemical parameters and morphology of all CSA nanoparticles were examined. The degree of conjugation of folic acid and cetuximab (CTXmab) was determined by UV-Visible spectroscopy and Bradford assay, respectively. Moreover, XPS analysis also supported the presence of the ligands on nanoparticles. The cellular-uptake study performed on A-549 cells demonstrated a significant enhancement in the uptake of dual-receptor targeted CSA nanoparticles than non-targeted and single-receptor targeted CSA nanoparticles. Further, CZT-loaded dual receptors targeted CSA nanoparticles also showed significantly lower IC

High resolution TEM studies revealed the spherical morphology of MxCe1-xO2 (M = Co, Fe or Ti, x = 0.05) particles with their size in the range of 8–11 nm. Raman, UV and PL spectroscopy analyses evidenced that oxygen vacancy concentration modified with the type of dopants. The concentration of vacancies in the Co0.05Ce0.95O2 sample was relatively higher and hence it had optimum magnetization value. The in-vitro cytotoxicity study for MxCe1-xO2 (M = Co, Fe or Ti, x = 0.05) nanoparticles against human lung adenocarcinoma (A549 cells) was conducted. The results suggested that at a 10 μg/mL concentration, the undoped CeO2 nanoparticles have shown cell viability up to 99%. In contrast, at the same concentration, the doped CeO2 such as Co0.05Ce0.95O2, Fe0.05Ce0.95O2 and Ti0.05Ce0.95O2 nanoparticles demonstrated the cell viability of ~97%. Furthermore, the samples displayed reliable biocompatibility up to 1000 μg/mL concentration. Interestingly, Co-doped CeO2 nanoparticles exhibited relatively higher biocompatibility against A549 cells at all concentrations. Further, the higher amount of vacancies might have improved the free radical scavenging effect and so the biocompatibility for the samples.

Graphical abstract Bioadhesive targeted delivery of Clofazimine against M. tuberculosis., Drug-resistant tuberculosis (TB) is one of the most lethal diseases, and it is imperative to exploit an advanced drug formulation for its effective treatment. This work aims to develop a mannose receptor-targeted bioadhesive chitosan nanoparticles for effective drug-resistant tuberculosis treatment. The clofazimine loaded chitosan nanoparticles were formulated; their size, charge, polydispersity (PDI), surface morphology, entrapment efficiency (EE) and in-vitro release pattern were established. Also, cellular uptake study on C2C12 cell lines and anti-mycobacterial activity against H37Rv (a standard strain of Mycobacterium tuberculosis) were evaluated. The particle sizes of formulated chitosan nanoparticles were in the range of 132–184 nm and EE was also found to be between 73 and 95%. The functionalization of bioadhesive chitosan nanoparticles with mannose was confirmed by infrared spectroscopy (FTIR). The uptake studies on the C2C12 cell lines showed that mannosylated nanoparticles were more efficiently internalized when compared to non-targeted nanoparticles. Further, luciferase reporter phage (LRP) assay against H37Rv strain showed that clofazimine nanoparticles were found to be 49.5 times superior in terms of inhibition and anti-mycobacterial activity than free clofazimine. This excellent activity might be attributed to enhanced drug delivery with a promising bioadhesion property of chitosan-based nanoparticles.

Aim: To design, optimize and evaluate docetaxel-loaded chitosan nanoparticles with (targeted) and without (nontargeted) cetuximab conjugation for the treatment of non-small-cell lung cancer (NSCLC). Materials & methods: Risk-assessment, optimization, in vitro characterizations, stability assessments, release studies, cell-culture studies were performed along with histopathology, pharmacokinetic and anticancer efficacy studies. Results: The nanoparticles of desired particle size (152.59 ± 3.90 nm to 180.63 ± 5.21 nm) which could sustain drug release for up to 70 h, were obtained. The cell-culture studies demonstrated the superiority of the formulations over Docel™. The pharmacokinetic evaluation showed the excellent systemic bioavailability of prepared NPs. The histopathology screening revealed lesser toxicity of both the nontargeted and targeted formulations. The targeted nanoformulation significantly reduced tumor growth than the nontargeted formulation and Docel. Conclusion: These results demonstrate the therapeutic potential of the prepared nanoformulation. After proper clinical validation, it could be a promising approach for the treatment of NSCLC.

X-ray powder diffraction (XRPD) is a unique, solid-state analytical tool used to study the 3D structure of small or macromolecules by their x-ray diffraction or scattering patterns. X-ray diffraction by a crystal reflects the periodicity of crystal architecture; any imperfections within the crystal architecture can be easily identified by its poor diffraction pattern. Recently, an open crystallography database reported that more than 85 % of drug compounds are crystalline and exist in different polymorphic states. Physicochemical properties of pharmaceutical drug products composed of active pharmaceutical ingredients (APIs) and excipients are interdependent on the physical state and forms in which APIs are distributed in excipients that determine the in-vivo and ex-vivo performance of the product. Amorphous APIs have relatively higher dissolution and bioavailability than crystalline form but with lower phase stability. During the formulation development and storage phase, the conversion is higher that largely impacts the bioavailability of the drug product. In this manuscript, we have presented the case study of itraconazole and apigenin; both are crystalline APIs, that, with the help of solid dispersion technology, are converted into amorphous drug products with enhanced oral bioavailability. The realtime monitoring of the physical form of API in the formulation was possible with the help of XRPD and other supporting data obtained from differential scanning calorimeter (DSC), which can be correlated with the dissolution and in-vivo performance of the formulation.

Aim: This work focused on the development of transferrin-conjugated theranostic liposomes consisting of docetaxel (DXL) and upconversion nanoparticles for the diagnosis and treatment of gliomas. Materials & methods: Upconversion nanoparticles and docetaxel-loaded theranostic liposomes were prepared by a solvent injection method. Formulations were analyzed for physicochemical properties, encapsulation efficiency, drug release, elemental analysis, cytotoxicity and fluorescence. Results: The particle size was around 200 nm with spherical morphology and an encapsulation efficiency of up to 75.93%, was achieved for liposomes with an in vitro drug release of 71.10%. The IC50 values demonstrated enhanced cytotoxicity on C6 glioma cells with targeted liposomes in comparison with nontargeted liposomes. Conclusion: Prepared theranostic liposomes may be promising for clinical validation after an in vitro and in vivo evaluation on cell lines and animals, respectively.

Recently the core-shell nanostructures are employed for various applications. In this trend, ϵ-Fe3N@Fe3O4 (INIO) magnetic nanoparticles (core/shell structured) were synthesized by a solvothermal process followed by calcination. The X-ray diffraction (XRD), selected area diffraction pattern (SAEDP), X-ray photoelectric spectroscopy (XPS) and Mossbauer spectroscopy validates the formation of the spherical core-shell structure of the ϵ-Fe3N@Fe3O4 nanoparticles having size range (5–32 nm). The saturation magnetization values for the sample at ±2 T field were around 128 and 99 Am2/kg at 5 and 300 K respectively. The values were higher than the known values for iron oxide nanoparticles. The pluronic acid (F-127) based ferrofluid of these nanoparticles, displayed excellent stability (Zeta potential values) and good heating ability (external AC magnetic fields). The best specific loss power was found to be around 90 W/g at 23 mT field. The cell viability with human lung adenocarcinoma A549 cells was observed to be 88 and 85% at 1 mg/mL for these nanoparticles after the treatment for 24 and 48 h respectively.

We report here the structural and biocompatibility studies of bare nanoparticles of θ-Fe3C and its ferrofluid, prepared using pluronic acid F127 as a stabilizer. For both the cases, this carbide was compatible (~ 80% cell viability after 48 h) with A549 human lung carcinoma cells up to a concentration of 2 mg/mL which was comparable to that of its magnetic iron oxide counterparts. The X-ray diffraction and transmission electron microscopy validated its orthorhombic phase having an average particle size of ~ 6 nm. The surface property of the θ-Fe3C sample was analyzed by X-ray photoelectron spectroscopy (XPS), which designates the existence of only Fe and C. The Mossbauer spectroscopy for the sample also verified this carbide phase. The room temperature saturation magnetization for the sample at 2 T was around 78.2 Am2/kg. This value was more than that of magnetic iron oxide nanoparticles of similar size. Its ferrofluid displayed substantial temperature rise with time during the magnetic hyperthermia experiment. Consequently, the obtained specific loss power, as well as intrinsic loss power values, were 46 W/g and 0.526 nHm2/kg, respectively, at a field of 23 mT and 261 kHz. Both the values indicated its suitability for magnetic hyperthermia application.

The light absorption and emission characteristics of DNA biodots (DNA-BD), along with biocompatibility, give them a high potential for use in various medical applications, particularly in diagnostic purpose. DNA, under high pressure and temperature, condenses to form luminescent biodots. The objective of this research is to develop DNA-biodots (BD) loaded and cetuximab conjugated targeted theranostic liposomes of etoposide for lung cancer imaging and therapy. Theranostic liposomes were prepared by using the solvent injection method and characterized for their particle size, polydispersity, zeta potential, encapsulation efficiency, and pH-dependent in-vitro release, SEM, TEM AFM, EDX, and XRD. The t50% (time at which 50% of the drug releases from the preparation) of the formulations was pH-dependent, with a significant increase in the release at lower pH (5.5). To kill A549 adenocarcinoma cells, the etoposide (control) required significantly (p

Microbial infections and antibiotic resistance are among the leading causes of morbidity and mortality worldwide. The bimetallic chitosan (CS)-capped gold-silver nanoparticles (CS-AuAg-NPs) were prepared by the seeded growth synthesis technique. The nanoparticles were optimized for particle size (PS), zeta potential (ZP) and antibacterial activity by Box–Behnken design at three levels and three factors. The developed CS-AuAg-NPs were polydispersed with mean hydrodynamic PS in the range of 55 – 289 nm and ZP ranges from +8.53 mV to +38.6 mV. The optimized CS-AuAg-NPs found to have a minimum inhibitory concentration and minimal bactericidal concentration of 1.625 ± 0.68 and 3.25 ± 0.74 µg ml−1 towards multidrug resistant (MDR) Staphylococcus aureus ATCC 25923 (MDR AT) and 3.25 ± 0.93 and 3.25 ± 0.86 µg ml−1 towards MDR S. aureus clinical isolate MDR1695 (MDR CI) strain, respectively. The CS-AuAg-NPs were much more effective against MDR AT and MDR CI compared to clindamycin standard. The live/dead assay of clinical isolates strain demonstrated significant reduction of bacterial cells ∼67.52 folds compared to control group in 12 h. The hemolysis study suggested that CS-AuAg-NPs were non-hemolytic and safer for application in the wound. Furthermore, CS-AuAg-NPs were distributed in the CS film, which showed 87% wound recovery after 7 d in mice model. Hence, we concluded that CS-AuAg-NPs was safer and more effective against MDR bacteria and capable of skin regeneration in the infected wound.

Currently available anti-thrombotic therapy for the prophylaxis and treatment of arterial and venous thrombosis includes intravenous administration of anti-thrombotic drugs which lead to severe bleeding risks such as cerebral hemorrhage and stroke. Targeting approaches that utilize nanosystems to reach the thrombus sites are emerging to increase the local effect of anti-thrombotic drugs, as well as to decrease these severe bleeding complications by diminishing the systemic availability of these drugs. This review emphasizes the emerging targeted nanomedicines (liposomes, micelles, polymeric nanoparticles, material bases nanoparticles and other biological vectors) for the prophylaxis and treatment of thrombotic events as well as multifunctional nanomedicines for theranostic applications. Nanomedicine offers a promising platform for a smart, safe, and effective approach for the management of thrombosis.

Novel glutathione (GSH) redox-sensitive thiolated vitaminE-PEG1000-succinate (TPGH-SH) was synthesized by conjugating TPGS with 4-amino thiophenol (4-ATP) and confirmed by FTIR and NMR studies. Following, docetaxel (DTX) loaded, cetuximab (CTB) conjugated redox sensitive TPGS-SH nanoparticles (TPGS-SH NP) were prepared by dialysis method and screened for size, charge, DTX entrapment, which revealed that size, surface charge and percent entrapment are in the range of 183–227 nm, +18 to +26 mV and 68–71%. SEM, TEM, AFM have reflected the spherical and uniform size of NP with a smooth surface. In-vitro release studies were performed in media containing different concentrations of GSH to study their effect on drug release and drug release of up to 94.5%, at pH 5.5, GSH 20 mM, is observed within 24 h. The pH/redox sensitivity studies revealed the better stability of NP at higher pH and lower GSH concentrations. In-vitro cytotoxicity, cellular uptake, migration and apoptotic assays, performed on A549 cells, have proved that targeted formulation produced higher cytotoxicity (significantly less IC50 value) and uptake and also prevented cell migration. Pharmacokinetic and histopathological screening were performed on CF rats, which demonstrated promising results. The in-vivo efficacy studies on benzo(a)pyrene induced mice lung cancer model showed that targeted TPGS-SH NP has significantly reduced the cell number than the model control.

Background: Since long back, it has been a matter of discussion regarding the role of peripheral blood vessels in the regulation of cardiorespiratory (CVR) system. Objective: The role of 5-HT3 and TRPV1 receptors present on perivascular nerves in elicitation of CVR reflexes was examined after intra-arterial instillation of bradykinin in urethane anesthetized rats. Materials and Methods: Femoral artery was cannulated retrogradely and was utilized for the instillation of saline/agonist/antagonist and recording of blood pressure (BP), using a double ported 24G cannula. BP, respiration and ECG were recorded for 30 min after bradykinin (1 μM) in the absence or presence of antagonists. Results: Instillation of bradykinin produced immediate hypotensive (40%), bradycardiac (17%), tachypnoeic (45%) and hyperventilatory (96%) responses of shorter latencies (5-8 s) favoring the neural mechanisms in producing the responses. In lignocaine (2%) pretreated animals, bradykinin- induced hypotensive (10%), bradycardiac (1.7%), tachypnoeic (13%) and hyperventilatory (13%) responses attenuated significantly. Pretreatment with ondansetron (100 μg/kg), 5-HT3-antagonist attenuated the hypotensive (10%), bradycardiac (1.7%), tachypnoeic (11%) and hyperventilatory (11%) responses significantly. Pretreatment with capsazepine (1 mg/kg), transient receptor potential vanilloid 1- antagonist blocked the hypotensive (5%), bradycardiac (1.2%), tachypnoeic (6%) and hyperventilatory (6%) responses significantly. Conclusion: In conclusion, presence of a nociceptive agent in the local segment of an artery evokes vasosensory reflex responses modulating CVR parameters involving TRPV1 and 5-HT3 receptors present on the perivascular sensory nerve terminals in anesthetized rats.

As the authors were working on similar projects on liposomes at the same time, the 3D figures of Fig. 3 bi and Fig. 3 bii were inadvertently misplaced.

Triple-negative breast (TNBC) cancer that is upregulated with epidermal growth factor receptor (EGFR), and devoid of both the hormonal receptors and epidermal growth factor receptor 2 (HER 2), has led to a concept of treating TNBC with EGFR-targeted therapeutics. The combination of paclitaxel (PTX) and piperine (PIP) may improve the bioavailability of paclitaxel for cancer therapy. TPGS (vit E-PEG 1000-succinate)-coated liposomes were prepared with PTX alone or in combination with PIP, and either with (targeted) or without (non-targeted) cetuximab (CTX) conjugation. The Bradford assay indicated that 75% of CTX has been conjugated on the liposomes. The size and percent encapsulation of PTX&PIP co-loaded liposomes were found to be in the range of 204 to 218 nm and 31–73%, respectively. The drug release rate was found to be higher at pH 5.5 in comparison with release at pH 6.4 and pH 7.4. Cellular uptake and toxicity studies on MDA-MB-231 cells showed that PTX&PIP co-loaded targeted liposomes have demonstrated superior uptake and cytotoxicity than their non-targeted counterparts. The IC50 values of both of the liposomal formulations were found to be significantly higher than PTX control. Indeed, combining PIP with PTX control has improved the cytotoxicity of PTX control, which proved the synergistic anticancer effect of PIP. Lyophilized liposomes showed an excellent stability profile with the size range between 189 and 210 nm. Plasma stability study revealed a slight increase in the particle size due to the adsorption of plasma proteins on the surface of liposomes. The long-term stability study also indicated that liposomes were stable at 4°C.

Nanotheranostics have demonstrated the development of advanced platforms that can diagnose brain cancer at early stages, initiate first-line therapy, monitor it, and if needed, rapidly start subsequent treatments. In brain nanotheranostics, therapeutic as well as diagnostic entities are loaded in a single nanoplatform, which can be further developed as a clinical formulation for targeting various modes of brain cancer. In the present review, we concerned about theranostic nanosystems established till now in the research field. These include gold nanoparticles, carbon nanotubes, magnetic nanoparticles, mesoporous silica nanoparticles, quantum dots, polymeric nanoparticles, upconversion nanoparticles, polymeric micelles, solid lipid nanoparticles and dendrimers for the advanced detection and treatment of brain cancer with advanced features. Also, we included the role of three-dimensional models of the BBB and cancer stem cell concept for the advanced characterization of nanotheranostic systems for the unification of diagnosis and treatment of brain cancer. In future, brain nanotheranostics will be able to provide personalized treatment which can make brain cancer even remediable or at least treatable at the primary stages.

The chitosan-folate conjugate was synthesized initially and confirmed by FTIR and NMR spectroscopic studies. Following, docetaxel (DXL) loaded non-targeted, single receptor and dual receptor (folate and EGFR) targeted chitosan nanoparticles were prepared and their shape, particle size, zeta-potential, surface morphology and texture were screened by SEM, TEM, AFM analyses. Surface chemistry analysis by XPS indeed confirmed the successful conjugation of folate and cetuximab on the targeted formulations. In-vitro analysis of dual-targeted chitosan nanoparticles has revealed their superior cytotoxicity against A-549 cells. The IC50 of dual receptor-targeted chitosan NP was almost 34 times lower than DXL control. In-vivo pharmacokinetic study on Wistar rats has demonstrated improved relative bioavailability of all NP in comparison to DXL control. The results illustrated that EGFR and folate dual targeted NP enhanced the cytotoxicity of DXL towards A-549 lung cancer cells and substantially improved DXL pharmacokinetics in rats.

The aim of this work was to formulate chitosan-folate conjugated multi-walled carbon nanotubes for the lung cancer targeted delivery of docetaxel. The chitosan-folate conjugate was synthesized and the conjugation was confirmed by Fourier transform infrared spectroscopy. The multi-walled carbon nanotubes were characterized for their particle size, polydispersity, zeta potential, surface morphology, drug encapsulation efficiency and in vitro release study. The in vitro cellular uptake, cytotoxicity, and cell cycle analysis of the docetaxel/coumarin-6 loaded multi-walled carbon nanotubes were carried out to compare the effectiveness of the formulations. The biocompatibility and safety of chitosan-folate conjugated multi-walled carbon nanotubes was analyzed by lung histopathology in comparison with marketed docetaxel formulation (Docel™) and acylated multi-walled carbon nanotubes. The cellular internalization study shown that the chitosan-folate conjugated multi-walled carbon nanotubes could be easily internalized into the lung cancer cells through a folate receptor-mediated endocytic pathway. The IC50 values exhibited that chitosan-folate conjugated multi-walled carbon nanotubes could be 89-fold more effective than Docel™ in human lung cancer cells (A549 cells).

The aim of this work was to prepare targeted bioadhesive d-α- tocopheryl glycol succinate 1000 (TPGS) micelles containing docetaxel (DTX) for brain targeted cancer therapy. Considering the unique bioadhesive feature of chitosan, herein, we have developed a synergistic transferrin receptor targeted bioadhesive micelles using TPGS conjugated chitosan (TPGS-chitosan), which target the overexpressed transferrin receptors of glioma cells for brain cancer therapy. The micelles were prepared by the solvent casting method and characterized for their particle size, polydispersity, zeta-potential, surface morphology, drug encapsulation efficiency, and in-vitro release. The IC50 values demonstrated transferrin receptor targeted TPGS-chitosan micelles could be 248 folds more effective than Docel™ after 24h treatment with the C6 glioma cells. Further, time dependent bioadhesive cellular uptake study indicated that a synergistic effect was achieved with the chitosan and transferrin in targeted TPGS-chitosan micelles through the biodhesive property of chitosan as well as transferrin receptor mediated endocytosis. The in-vivo pharmacokinetic results demonstrated that relative bioavailability of non-targeted and targeted micelles were 2.89 and 4.08 times more effective than Docel™ after 48h of treatments, respectively.

This work was aimed to formulate transferrin (Tf) receptor targeted gold based theranostic liposomes which contain both docetaxel (DCX) and glutathione reduced gold nanoparticles (AuGSH) for brain-targeted drug delivery and imaging. AuGSH was prepared by reducing chloroauric acid salt using glutathione. The co-loading of DCX and AuGSH into liposomes was achieved by the solvent injection technique, and Tf was post-conjugated on the surface of the liposomes using carboxylated Vit-E TPGS (TPGS-COOH) as a linker. The liposomes were characterized for various parameters such as size, shape, surface charge, and drug release. The Tf receptor targeted gold liposomes were evaluated for the cytotoxicity by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) based colorimetric assay and in-vitro qualitative cellular uptake studies using confocal microscopy. The in-vivo site specific delivery of DCX was analyzed by the brain distribution study of DCX in comparison with marketed formulation (Docel™). A sustained drug release of about 70% was observed from liposomes in the span of 72 h. The in-vivo results demonstrated that targeted gold liposomes were able to deliver DCX into the brain by 3.70, 2.74 and 4.08-folds higher than Docel™ after 30, 120 and 240 min of the treatment, respectively. Besides, the results of these studies have suggested the feasibility of Tf decorated AuGSH and DCX co-loaded liposomes as a promising platform for targeted nano-theranostics.

Biofilm resistance is one of the severe complications associated with chronic wound infections, which impose extreme microbial tolerance against antibiotic therapy. Interestingly, deoxyribonuclease-I (DNase-I) has been empirically proved to be efficacious in improving the antibiotic susceptibility against biofilm-associated infections. DNase-I hydrolyzes the extracellular DNA, a key component of the biofilm responsible for the cell adhesion and strength. Moreover, silver sulfadiazine, a frontline therapy in burn wound infections, exhibits delayed wound healing due to fibroblast toxicity. In this study, a chitosan gel loaded with solid lipid nanoparticles of silver sulfadiazine (SSD-SLNs) and supplemented with DNase-I has been developed to reduce the fibroblast cytotoxicity and overcome the biofilm-imposed resistance. The extensive optimization using the Box-Behnken design (BBD) resulted in the formation of SSD-SLNs with a smooth surface as confirmed by scanning electron microscopy and controlled release (83%) for up to 24 h. The compatibility between the SSD and other formulation excipients was confirmed by Fourier transform infrared, differential scanning calorimetry, and powder X-ray diffraction studies. Developed SSD-SLNs in combination with DNase-I inhibited around 96.8% of biofilm of Pseudomonas aeruginosa as compared to SSD with DNase-I (82.9%). In line with our hypothesis, SSD-SLNs were found to be less toxic (cell viability 90.3 ± 3.8% at 100 μg/mL) in comparison with SSD (Cell viability 76.9 ± 4.2%) against human dermal fibroblast cell line. Eventually, the results of the in vivo wound healing study showed complete wound healing after 21 days' treatment with SSD-SLNs along with DNase-I, whereas marketed formulations SSD and SSD-LSNs showed incomplete healing after 21 days. Data in hand suggest that the combination of SSD-SLNs with DNase-I is an effective treatment strategy against the biofilm-associated wound infections and accelerates wound healing.

The aim of this work was to formulate RGD-TPGS decorated theranostic liposomes, which contain both docetaxel (DTX) and quantum dots (QDs) for brain cancer imaging and therapy. RGD conjugated TPGS (RGD-TPGS) was synthesized and conjugation was confirmed by Fourier transform infrared (FTIR) spectroscopy and electrospray ionisation (ESI) mass spectroscopy (ESI-MS). The theranostic liposomes were prepared by the solvent injection method and characterized for their particle size, polydispersity, zeta-potential, surface morphology, drug encapsulation efficiency, and in-vitro release study. Biocompatibility and safety of theranostic liposomes were studied by reactive oxygen species (ROS) generation study and histopathology of brain. In-vivo study was performed for determination of brain theranostic effects in comparison with marketed formulation (Docel™) and free QDs. The particle sizes of the non-targeted and targeted theranostic liposomes were found in between 100 and 200nm. About 70% of drug encapsulation efficiency was achieved with liposomes. The drug release from RGD-TPGS decorated liposomes was sustained for more than 72h with 80% of drug release. The in-vivo results demonstrated that RGD-TPGS decorated theranostic liposomes were 6.47- and 6.98-fold more effective than Docel™ after 2h and 4h treatments, respectively. Further, RGD-TPGS decorated theranostic liposomes has reduced ROS generation effectively, and did not show any signs of brain damage or edema in brain histopathology. The results of this study have indicated that RGD-TPGS decorated theranostic liposomes are promising carrier for brain theranostics.

The aim of this study was to develop multi-walled carbon nanotubes (MWCNT) which were covalently conjugated with transferrin by carbodiimide chemistry and loaded with docetaxel as a model drug for effective treatment of lung cancer in comparison with the commercial docetaxel injection (Docel™). d-Alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS) was used as amphiphilic surfactant to improve the aqueous dispersity and biocompatibility of MWCNT. Human lung cancer cells (A549 cells) were employed as an in-vitro model to access cellular uptake, cytotoxicity, cellular apoptosis, cell cycle analysis, and reactive oxygen species (ROS) of the docetaxel/coumarin-6 loaded MWCNT. The cellular uptake results of transferrin conjugated MWCNT showed higher efficiency in comparison with free C6. The IC50 values demonstrated that the transferrin conjugated MWCNT could be 136-fold more efficient than Docel™ after 24h treatment with the A549 cells. Flow cytometry analysis confirmed that cancerous cells appeared significantly (P

The aim of this work was to develop multi-walled carbon nanotubes (MWCNT), which were coated or covalently conjugated with d-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS), and loaded docetaxel as a model drug for effective treatment to lung cancer in comparison with the commercial docetaxel injection (Docel™). The human lung cancer cells (A549 cells) were employed as an in-vitro model to access cellular uptake, cytotoxicity, cellular apoptosis, cell cycle analysis, and reactive oxygen species (ROS) study of the docetaxel/coumarin-6 loaded MWCNT. The safety of MWCNT formulations were studied by the measurements of alkaline phosphatase (ALP), lactate dehydrogenase (LDH) and total protein levels in bronchoalveolar lavage (BAL) fluid of rats after the treatments. The IC50 values demonstrated that the TPGS conjugated MWCNT could be 80 folds more effective than Docel™ after 24h treatment with the A549 cells. Flow cytometry analysis confirmed that cancerous cells were appeared significantly (P

The recent progresses in tissue engineering and nanomaterial-based therapeutics/theranostics have led to the ever increasing utilization of 3D in vitro experimental models as the bona fide culture systems to evaluate the therapeutic/theranostic effects of nanomedicine. Compared to the use of conventional 2D culture platforms, 3D biomimetic cultures offer unmatched advantages as relevant physiological and pathological elements can be incorporated to allow better characterization of the engineered bio-nanomaterials in the targeted tissue-specific microenvironment. In this Feature Article, the current state-of-the-art 3D in vitro models that have been developed for the evaluation of biosafety and efficacy of nano- therapeutics/theranostics targeting the colon, blood–brain barrier (BBB), lungs, skin tumor models to bridge the nanomedicine bench to pre-clinical ravine are reviewed. Furthermore, the critical physicochemical parameters of the bio-nanomaterials that govern its transport and biodistribution in a complex 3D microenvironment will be highlighted. The major challenges and future prospects of evaluating nanomedicine in the third dimension will also be discussed.