A peek behind the curtain in the diagnosis and management of COVID­19­Associated Mucormycosis (CAM).

Coronavirus disease 2019 (COVID-19)-associated mucormycosis (CAM) is responsible for a high mortality rate due to its unique and severe host-pathogen interactions. Critically ill or immunocompromised COVID-19 patients are more prone to suffer from aggressive mycoses. Probable victims include those with uncontrolled diabetes mellitus (DM), metabolic acidosis, prolonged neutropenia, increased ferritin levels, hypoxia, and prolonged hospitalization with/without mechanical ventilators and corticosteroids administration. The current review aims to outline the journey of patients with CAM as well as the advantages and disadvantages of the currently available diagnostic techniques. It also discussed the current status of treatment options and caveats in the management of mucormycosis. Multidisciplinary team, early diagnosis, controlling the predisposing condition(s), complete surgical debridement, effective antifungal therapies (e.g., amphotericin B, isavuconazole, and posaconazole), and implementing antifungal stewardship programs are imperative in CAM cases.

Structure-Activity-Relationship and Mechanistic Insights for Anti-HIV Natural Products.

Acquired Immunodeficiency Syndrome (AIDS), which chiefly originatesfroma retrovirus named Human Immunodeficiency Virus (HIV), has impacted about 70 million people worldwide. Even though several advances have been made in the field of antiretroviral combination therapy, HIV is still responsible for a considerable number of deaths in Africa. The current antiretroviral therapies have achieved success in providing instant HIV suppression but with countless undesirable adverse effects. Presently, the biodiversity of the plant kingdom is being explored by several researchers for the discovery of potent anti-HIV drugs with different mechanisms of action. The primary challenge is to afford a treatment that is free from any sort of risk of drug resistance and serious side effects. Hence, there is a strong demand to evaluate drugs derived from plants as well as their derivatives. Several plants, such as Andrographis paniculata, Dioscorea bulbifera, Aegle marmelos, Wistaria floribunda, Lindera chunii, Xanthoceras sorbifolia and others have displayed significant anti-HIV activity. Here, weattempt to summarize the main results, which focus on the structures of most potent plant-based natural products having anti-HIV activity along with their mechanisms of action and IC50 values, structure-activity-relationships and important key findings.

Development of docetaxel nanocapsules for improving in vitro cytotoxicity and cellular uptake in MCF-7 cells.

The aim of this study was to fabricate docetaxel loaded nanocapsules (DTX-NCs) with a high payload using Layer-by-Layer (LbL) technique by successive coating with alternate layers of oppositely charged polyelectrolytes. Developed nanocapsules (NCs) were characterized in terms of morphology, particle size distribution, zeta potential (ζ-potential), entrapment efficiency and in vitro release. The morphological characteristics of the NCs were assessed using transmission electron microscopy (TEM) that revealed coating of polyelectrolytes around the surface of particles. The developed NCs successfully attained a submicron particle size while the ζ-potential of optimized NCs alternated between (+) 34.64 ± 1.5 mV to (-) 33.25 ± 2.1 mV with each coating step. The non-hemolytic potential of the NCs indicated the suitability of the developed formulation for intravenous administration. A comparative study indicated that the cytotoxicity of positively charged NCs (F4) was significant higher (p < 0.05) rather than negative charged NCs (F3), plain drug (DTX) and marketed preparation (Taxotere®) when evaluated in vitro on MCF-7 cells. Furthermore, cell uptake studies evidenced a higher uptake of positive NCs (≥1.2 fold) in comparison to negative NCs. In conclusion, formulated NCs are an ideal vehicle for passive targeting of drugs to tumor cells that may result in improved efficacy and reduced toxicity of encapsulated drug moiety.

Synthesis of novel celecoxib analogues by bioisosteric replacement of sulfonamide as potent anti-inflammatory agents and cyclooxygenase inhibitors.

Two series of celecoxib analogues having 1,5-diaryl relationship were synthesized. The key strategy of the molecular design was oriented towards exploring bioisosteric modifications of the sulfonamide moiety of celecoxib. First series (2a-2i) of celecoxib analogues bearing cyano functionality in place of sulfonamide moiety was synthesized by the reaction of appropriate trifluoromethyl-ß-diketones (5a-5i) with 4-hydrazinylbenzonitrile hydrochloride (4) in ethanol. Cyano moiety of pyrazoles 2 was then converted into corresponding carbothioamides 3 by bubbling H2S gas in the presence of triethylamine. All the synthesized compounds (2a-2i and 3a-3i) were screened for their in vivo anti-inflammatory (AI) activity using carrageenan-induced rat paw edema assay. COX-1 and COX-2 inhibitory potency was evaluated through in vitro cyclooxygenase (COX) assays. Compounds 2a, 2b, 2c, 2e and 3c showed promising AI activity at 3-4h after the carrageenan injection that was comparable to that of the standard drug indomethacin. Although compounds 3d, 3e and 3f exhibited more pronounced COX-2 inhibition but they also inhibit COX-1 effectively thus being less selective against COX-2. Three compounds 2a, 2f and 3a were found to have a COX profile comparable to the reference drug indomethacin. However 2e, 3b, 3c and 3i compounds were the most potent selective COX-2 inhibitors of this study with 3b showing the best COX-2 profile. In order to better rationalize the action and the binding mode of these compounds, docking studies were carried out. These studies were in agreement with the biological data.

Templated ultrathin polyelectrolyte microreservoir for delivery of bovine serum albumin: fabrication and performance evaluation.

The aim of the study was to develop ultrathin polyelectrolyte microreservoir (UPM) using two combinations of synthetic/synthetic (S/s; poly(allylamine hydrochloride) (PAH)/sodium poly(styrenesulfonate)) and synthetic/natural (S/n; PAH/sodium alginate) polyelectrolytes over spherical porous CaCO(3) core particles (CP) followed by core removal and to evaluate its biocompatibility and integrity of loaded model protein bovine serum albumin (BSA). A novel process for synthesis of CP was developed to obtain maximum yield of monodisperse vaterite (spherical) polymorph. The prepared UPM was characterized for surface morphology, layer-by-layer growth, pay load efficiency, integrity of BSA, as well as viability and cell adhesion using murine J 774 macrophages (Φ). In vitro release profile revealed that both S/s and S/n UPM were able to provide sufficient diffusion barrier to release protein at physiological pH. It has been observed that S/n UPM are fully biocompatible due to obvious reason of using natural polymer. In a separate experiment, the S/s UPM surface was modified with pluronic F-68 to tune biocompatibility which provides evidences for safety and tolerability of the S/s UPM as well. In nutshell, the proposed system could successfully be used for the delivery of proteins, and moreover, the system can be tailored to impart desired properties at any stage of layering especially in terms of drug release and to retain the integrity of proteins.

In search of therapeutic candidates for HIV/AIDS: rational approaches, design strategies, structure-activity relationship and mechanistic insights.

The HIV/AIDS pandemic is a serious threat to the health and development of mankind, which has affected about 37.9 million people worldwide. The increasing negative health, economic and social impacts of this disease have led to the search for new therapeutic candidates for the mitigation of AIDS/HIV. However, to date, there is still no treatment that can cure this disease. Furthermore, the clinically available drugs have numerous severe side effects. Hence, the synthesis of novel agents from natural leads is one of the rational approaches to obtain new drugs in modern medicinal chemistry. This review article is an effort to summarize recent developments with regards to the discovery of novel analogs with promising biological potential against HIV/AIDS. Herein, we also aim to discuss prospective directions on the progress of more credible and specific analogues. Besides presenting design strategies, the present communication also highlights the structure-activity relationship together with the structural features of the most promising molecules, their IC50 values, mechanistic insights and some interesting key findings revealed during their biological evaluation. The interactions with the amino acid residues of the enzymes responsible for HIV-1 inhibition are also discussed. This collection will be of great interest for researchers working in this area.

The Undiscovered Potential of Essential Oils for Treating SARS-CoV-2 (COVID-19).

On 11th March 2020, the World Health Organisation (WHO) announced a pandemic caused by a novel beta-coronavirus SARS-CoV-2, designated COVID-19. The virus emerged in December 2019 in Wuhan, China, has spread across the world as a global pandemic. The traditional use of medicines from plants can be traced back to 60,000 years. Global interest in the development of drugs from natural products has increased greatly during the last few decades. Essential oils (EOs) have been studied through the centuries and are known to possess various pharmaceutical properties. In the present review, we have highlighted the current biology, epidemiology, various clinical aspects, different diagnostic techniques, clinical symptoms, and management of COVID-19. An overview of the antiviral action of EOs, along with their proposed mechanism of action and in silico studies conducted, is described. The reported studies of EOs' antiviral activity highlight the baseline data about the additive and/or synergistic effects among primary or secondary phytoconstituents found in individual oils, combinations or blends of oils and between EOs and antiviral drugs. It is hoped that further research will provide better insights into EOs' potential to limit viral infection and aid in providing solutions through natural, therapeutically active agents.

Galactose-grafted chylomicron-mimicking emulsion: evaluation of specificity against HepG-2 and MCF-7 cell lines.

OBJECTIVES: A chylomicron-mimicking lipid emulsion was prepared and loaded with paclitaxel (paclitaxel-CM) and was further grafted with galactose (paclitaxel-GCM) using palmitoyl-galactosamine, which was synthesized by reacting galactosamine hydrochloride with N-hydroxy succinimide ester of palmitic acid. Palmitoyl-galactosamine was used as a ligand for asialoglycoprotein receptors. METHODS: The uptake characteristics of the emulsions were evaluated in HepG-2 cells (human hepatocarcinaoma), which express asialoglycoprotein receptors, and MCF-7 (breast cancer) cells, which are devoid of these receptors. KEY FINDINGS: The incorporation efficiency of paclitaxel-CM was 68.05 +/- 4.80% and that of paclitaxel-GCM was 72.10 +/- 3.93% when the emulsion was prepared with 7.5% (w/w) paclitaxel/lipid phase. The globule size of paclitaxel-GCM and paclitaxel-CM was 124 +/- 8.67 and 96.45 +/- 5.78 nm, respectively. The release of paclitaxel from both of the formulations was fairly sustained: 50 +/- 3.2% of paclitaxel in 24 h. The cytotoxicity and uptake of paclitaxel-GCM were significantly higher (P < 0.05) in HepG-2 cells than MCF-7 cells, while for paclitaxel-CM cytotoxicity and uptake were similar in the two cell lines. This study clearly demonstrates that upon surface modification palmitoyl-galactosamine remains an integral part of the formulation. Paclitaxel solubility can be improved using optimum paclitaxel/lipid phase ratios. The paclitaxel-GCM formulation recognizes asialoglycoprotein receptors overexpressed on HepG-2 cells. CONCLUSIONS: Under our experimental conditions, the proposed paclitaxel-GCM formulation is an ideal delivery vehicle for specific targeting to liver cancer cells, which is anticipated to result in improved efficacy and reduced toxicity to normal cells.

Uptake of biodegradable gel-assisted LBL nanomatrix by Leishmania donovani-infected macrophages.

The aim of this study was to develop novel gel-assisted layer-by-layer (LBL) nanomatrix with high payload of doxorubicin (DOX) and to assess its efficacy against Leishmania donovani. The biodegradable LBL nanomatrix was fabricated using LBL technique using polyions (protamine and sodium alginate) on decomposable core. The developed system was characterized in vitro in terms of layer-by-layer growth and payload efficiency. The efficacy of optimized formulations was evaluated against L. donovani strain in terms of inhibitory concentration (IC50). Uptake studies by infected macrophages were investigated both qualitatively and quantitatively using fluorescence microscopy and flow cytometry. The autogelling property subsequent to core removal inside the nanomatrix resulted in high payload efficiency of DOX (i.e., >70%). The reversal in charge followed the same trend with additional layers, and the magnitude of the charge remained constant up to five complete bilayers of polyions. The DOX can be effectively encapsulated, delivered, and subsequently taken up by L. donovani-infected macrophage cells. The matrix is completely internalized into macrophages showing improved efficacy (IC50 of formulation is almost

Advanced Glycation End Products (AGEs), Glutathione and Breast Cancer: Factors, Mechanism and Therapeutic Interventions.

BACKGROUND: Advanced Glycation End products (AGEs) are basically the end result of glycation of proteins and/or lipids in the presence of sugars. Specific cases of hyperglycemia have been reported with increased propensity of generation of AGEs. Many chronic and deadly diseases such as diabetes, cancer and neurodegenerative disorders have been known to be caused as a result of generation of AGEs. The role of glutathione (GSH) metabolism and its intricate association with AGEs have also been well established in breast cancer prognosis and treatment. To understand the etiology, mechanism and production of AGEs along with clinical relevance of Receptors for Advanced Glycation End-products (RAGE) and RAGE ligands, their interplay with GSH is of paramount importance especially in relation to breast cancer. METHODS: The available literature using PubMed, National Library of Medicine database, Web of Science and SCOPUS indexed, Science Direct and other prestigious journals have been systematically reviewed using the keywords: advanced glycation end-products, breast cancer, glutathione RAGE, and AGEs inhibitors. This narrative review of all the relevant papers with significant citations has led us to have greater insight into the action mechanism and potential therapeutic significance of AGEs inhibitors. RESULTS: Targeting breast cancer with the specific immunoglobulins and with other therapeutic interventions is needed to inhibit the generation of AGEs and manage glutathione expression, thus having strong implications in the management of breast cancer. Many RAGE ligands such as HMGB1, S100P, S100A8, S100A9 etc. have been known to enhance RAGE expression which may further lead to increased proliferation, migration and metastatic nature of tumor cells. Hence, RAGE and RAGE ligands in a close linkup with GSH may prove to be effective therapeutic markers of severity of breast cancer and for angiogenesis of tumor. CONCLUSION: This review provides a strong platform to comprehend the etiology, mechanism and production of AGEs and glutathione along with the agents which can block their production, paving a way for the therapeutic intervention and an amicable solution to treat and manage breast cancer.

Double Edge Sword Behavior of Carbendazim: A Potent Fungicide With Anticancer Therapeutic Properties.

BACKGROUND: A number of benzimidazole derivatives such as benomyl and carbendazim have been known for their potential role as agricultural fungicides. Simultaneously carbendazim has also been found to inhibit proliferation of mammalian tumor cells specifically drug and multidrug resistant cell lines. OBJECTIVE: To understand the dual role of Carbendazim as a fungicide and an anticancer agent, the study has been planned referring to the earlier studies in literature. RESULTS: Studies carried out with fungal and mammalian cells have highlighted the potential role of carbendazim in inhibiting proliferation of cells, thereby exhibiting therapeutic implications against cancer. Because of its promising preclinical antitumor activity, Carbendazim had undergone phase I clinical trials and is under further clinical investigations for the treatment of cancer. A number of theoretical interactions have been pinpointed. There are many anticancer drugs in the market, but their usefulness is limited because of drug resistance in a significant proportion of patients. The hunger for newer drugs drives anticancer drug discovery research on a global platform and requires innovations to ensure a sustainable pipeline of lead compounds. CONCLUSION: Current review highlights the dual role of carbendazim as a fungicide and an anticancer agent. Further, the harmful effects of carbendazim and emphasis upon the need for more pharmacokinetic studies and pharmacovigilance data to ascertain its clinical significance, have also been discussed.

Aryl Butenes Active against K562 Cells and Lacking Tyrosinase Inhibitory Activity as New Leads in the Treatment of Leukemia.

BACKGROUND & OBJECTIVE: The inhibitory effects of four series of aryl butene derivatives, active against breast cancer, on the monophenolase activity of tyrosinase, in melanin-free ink from Sepia officinalis, have been studied. Hydroxytamoxifen 1, ferrociphenol 17 and several aryl butene analogs have shown strong antiproliferative activity on hormone-dependent and hormone-independent breast cancer cells and were evaluated in leukemia K562 cell proliferation. Their potential to induce skin depigmentation by evaluating their anti-tyrosinase activity was also estimated. In order to better rationalize the tyrosinase inhibitory action and the binding mode of the compounds, docking studies were carried out. CONCLUSION: Hydroxytamoxifen and some aryl butenes showed strong antiproliferative effects against K562 cells at 1 µM without showing tyrosinase inhibition. If phenolic compounds 16 and 17 showed the best antiproliferative activity on K562, Hydroxytamoxifen and compounds 5, 10, 20 and 21 have been identified as candidates for further development against chronic myeloid leukemia (CML), and are predicted to not induce depigmentation of the skin, a side effect encountered with imatinib, conventionally used for the treatment of CML.

Antitumour, acute toxicity and molecular modeling studies of 4-(pyridin-4-yl)-6-(thiophen-2-yl) pyrimidin-2(1H)-one against Ehrlich ascites carcinoma and sarcoma-180.

In an effort to discover an effective and selective antitumour agent, synthesis and anti-cancer potential of 4-(pyridin-4-yl)-6-(thiophen-2-yl) pyrimidin-2(1H)-one (SK-25), which has been reported earlier by us with significant cytotoxicity towards MiaPaCa-2 malignant cells, with an IC50 value of 1.95 µM and was found to instigate apoptosis. In the present study, the antitumour efficacy of SK-25 was investigated on Ehrlich ascites tumour (EAT, solid), Sarcoma 180 (solid) tumour and Ehrlich ascites carcinoma. The compound was found to inhibit tumour development by 94.71% in Ehrlich ascites carcinoma (EAC), 59.06% in Ehrlich tumour (ET, solid) and 45.68% in Sarcoma-180 (solid) at 30 mg/kg dose. Additionally, SK-25 was established to be non-toxic at a maximum tolerated dose of 1000 mg/kg in acute oral toxicity in Swiss-albino mice. Computer-based predictions also show that the compounds could have an interesting DMPK profile since all 51 computed physicochemical parameters fall within the recommended range for 95% of known drugs. The current study provides insight for further investigation of the antitumour potential of the molecule.

Developments in synthesis of the anti-inflammatory drug, celecoxib: a review.

Celecoxib, a tricyclic compound having pyrazole ring exhibits an excellent level of antiinflammatory action against COX-2 enzymes and some of its analogs act as anticancer and antibacterial agents. Various efficient routes and different improved processes for the synthesis of this drug have already been disclosed in the literature. However, there is a need for further developments in the present scenario of achieving cost effective synthetic technologies to celecoxib with high purity accompanied by excellent yield. Therefore, an effort has been made to summarize briefly the different methods of preparation of Celecoxib with their advantages or disadvantages that have been reported in various patents up to 2013. The present review would be beneficial for scientific community for further developments in the synthetic methodologies for Celecoxib and to explore some novel celecoxib based biologically active agents.

Osteogenic efficacy enhancement of kaempferol through an engineered layer-by-layer matrix: a study in ovariectomized rats.

AIM: A layer-by-layer matrix (LBL) comprising kaempferol (LBL-KEM) was prepared for improved osteogenic action. MATERIALS & METHODS: The LBL-KEM consisted of alternate layers of sodium alginate and protamine sulfate, which were sequentially deposited on the preformed kaempferol (KEM)-loaded CaCO3 core (CaCO3-KEM) by LBL self-assembly. The LBL matrix developed was evaluated for layer growth by ζ-potential and size alterations after self-assembly of each layer. Its physicochemical properties and intestinal absorption pattern were characterized and its pharmacokinetic behavior, mineralization of bone marrow cells, bone mineral density, bone strength, microcrack formation and estrogenicity were evaluated after oral administration. RESULTS: The entrapment efficiency of KEM was 94 ± 2% and the cumulative %KEM released from LBL-KEM was 19.2 and 63.5% at pH 1.4 and 7.4, respectively, after 24 h. Stepwise polyelectrolyte assembly onto initially positively charged particles (+21.2 mV) resulted in alterations between -28.5 and +10.9 mV. A final ζ-potential of -8.9 mV was obtained after terminal surface modification with sodium deoxycholate. Fluorescein isothiocyanate-labeled LBL matrix was diffused into the basolateral lacteal region upon oral administration to rats. The area under the KEM serum concentration curve following oral administration of LBL-KEM to rats was 2479 ± 682 ng·h/ml, nearly twofold higher than free KEM. The concentration-time profile in bone marrow indicated improved penetration and retention of KEM on administration of LBL-KEM. Treatment with LBL-KEM restored bone mineralization, bone mineral density, microcrack formation and empty osteocyte lacunae density in ovariectomized (OVx) rats, which was significantly (p < 0.05) improved in femoral diaphysea, tibial head and vertebrae compared with free KEM treatment. Administration of LBL-KEM to growing female rats for 4 weeks resulted in no estrogenicity when compared with OVx rats. CONCLUSION: The data suggests that LBL matrix enhanced drug delivery, improved pharmacokinetics and maintained better bone quality under OVx conditions.

In vivo efficacy studies of layer-by-layer nano-matrix bearing kaempferol for the conditions of osteoporosis: a study in ovariectomized rat model.

A prototype formulation based on layer-by-layer (LbL) nano-matrix was developed to increase bioavailability of kaempferol with improved retention in bone marrow to achieve enhanced bone formation. The layer-by-layer nano-matrix was prepared by sequential adsorption of biocompatible polyelectrolytes over the preformed kaempferol-loaded CaCO(3) template. The system was pharmaceutically characterized and evaluated for osteogenic activity in ovariectomized (OVx) rats. Data have been compared to the standard osteogenic agent parathyroid hormone (PTH). Single oral dose of kaempferol loaded LbL nano-matrix formulation increased bioavailability significantly compared to unformulated kaempferol. Three months of Formulated kaempferol administration to osteopenic rats increased plasma and bone marrow Kaempferol levels by 2.8- and 1.75-fold, respectively, compared to free Kaempferol. Formulated Kaempferol increased bone marrow osteoprogenitor cells, osteogenic genes in femur, bone formation rate, and improved trabecular micro-architecture. Withdrawal of Formulated kaempferol-in OVx rats resulted in the maintenance of bone micro-architecture up to 30days, whereas micro-architectural deterioration was readily observed in OVx rats treated with unformulated kaempferol-within 15days of withdrawal. The developed novel formulation has enhanced anabolic effect in osteopenic rats through increased stimulatory effect in osteoblasts. Treatment post-withdrawal sustenance of formulated kaempferol could become a strategy to enhance bioavailability of flavanoids.

Ciprofloxacin surf-plexes in sub-micron emulsions: a novel approach to improve payload efficiency and antimicrobial efficacy.

The aim of this study was to investigate antimicrobial efficacy and pharmacokinetic profile of ciprofloxacin (CFn) loaded oil-in-water (o/w) submicron emulsion (SE-CFn). This study emphasized on development of hydrophobic ion-pair complexes of CFn with sodium deoxycholate (SDC) [CFn-SDC], which was incorporated in the core of SE (SE-CFn-SDC). SE-CFn-SDC was characterized for globulet size (278±12 nm), zeta potential (-25.3±1 mV), viscosity (2.6±0.3 cP), transmission electron microscopy (TEM), drug entrapment and for in vitro release profile. The entrapment efficiency (EE) was significantly improved (≥80%; p≤0.05) on ion-pairing while it was merely 27.2±3.1% for free CFn. The cytotoxicity studies of formulations on J774 macrophage cells showed that more than 90±3% of cells were viable, even at high concentration (100 µg/ml). SE-CFn-SDC was further modified with cationic inducer chitosan (SE-CH-CFn-SDC), which showed almost twofold and fourfold enhancement in antimicrobial efficacy as compared to SE-CFn-SDC and SE-CFn, respectively when tested in vitro against E. coli, S. aureus, and P. aeruginosa. When tested in male Balb/c mice, the AUC(0-24h) of SE-CH-CFn-SDC (23.27±2.8 h µg/ml) was found to be 1.7-fold and 5-fold higher as compared to SE-CFn-SDC (13.17±0.88 h µg/ml) and CFn solution (4.70±0.77 h µg/ml), respectively. The study demonstrates that surfactant based ionic complex formation incorporated in surface modified submicron emulsion is a promising approach to improve payload efficiency of poorly water soluble drugs with improved antimicrobial efficacy and pharmacokinetic profile.

Investigations on cellular interaction of polyelectrolyte based nano-walled reservoir using MCF-7 cell lines: a novel chemotherapeutic approach.

OBJECTIVES: A polyelectrolyte (PE) based nano-walled reservoir (NwR) was developed using alternate deposition of natural polyions on a decomposable core (CaCO(3)). The system was charged with paclitaxel (PTX) using the trigger property of an organic solvent (NwR-PTX). In addition, the surface of the nano-walled reservoir was modified with PE-PEG2000 (NwR-PTX-PEG)) in order to investigate any changes in the interaction of surface-modified polyelectrolyte shells with breast cancer cells, since surface chemistry greatly influences the performance of microcapsules in the biological environment. METHODS: The surface modification was confirmed by differential scanning calorimetry studies, which showed a shifting of the endothermic peak after pegylation. Layer-by-layer (LBL) growth of the system was confirmed by the sequential change in the zeta-potential. The release of paclitaxel from the formulations followed first order kinetics (r(2) = 0.9), indicating matrix diffusion. The interaction of NwR-PTX with MCF-7 cell lines was investigated by coating the system with FITC-dextran (NwR-PTX-FITC) and quantitated using flow cytometry. KEY FINDINGS: Cellular uptake of positively charged NwR reached 56% after 4 h and 76% after 24 h. This was reduced significantly after pegylation. The negatively charged NwR reached only 49% after 24 h. CONCLUSIONS: This study opens the possibility of specific targeting of tumour cells that can control the release of chemotherapeutic agent either by means of a physiological or chemical trigger. This suggests potential application of this system as a novel approach for the delivery of chemotherapeutic agents.