Folate receptor-mediated delivery system based on chitosan coated polymeric nanoparticles for combination therapy of breast cancer.

Combination therapy using two or more drugs with different mechanisms of action is an effective strategy for treating cancer. This is because of the synergistic effect of complementary drugs that enhances their effectiveness. However, this approach has some limitations, such as non-specific distribution of the drugs in the tumor and the occurrence of dose-dependent toxicity to healthy tissues. To overcome these issues, we have developed a folate receptor-mediated co-delivery system that improves the access of chemotherapy drugs to the tumor site. We prepared a nanoplatform by encapsulating paclitaxel (PTX) and curcumin (CUR) in poly(caprolactone)-poly(ethylene glycol)-poly(caprolactone) (PCL-PEG-PCL) co-polymer using a double emulsion method and coating nanoparticles with pH-responsive chitosan-folic acid (CS-FA) conjugate. The nanocarrier's physicochemical properties were studied, confirming successful preparation with appropriate size and morphology. PTX and CUR could be released synchronously in a controlled and acid-facilitated manner. The dual drug-loaded nanocarrier exhibited excellent anti-tumor efficiency in MDA-MB-231 cells in vitro. The active targeting effect of FA concluded from the high inhibitory effect of dual drug-loaded nanocarrier on MDA-MB-231 cells, which have overexpressed folate receptors on their surface, compared to Human umbilical vein endothelial cells (HUVEC). Overall, the nanoengineered folate receptor-mediated co-delivery system provides great potential for safe and effective cancer therapy.

Paclitaxel and its semi-synthetic derivatives: comprehensive insights into chemical structure, mechanisms of action, and anticancer properties.

Cancer is a disease that can cause abnormal cell growth and can spread throughout the body. It is among the most significant causes of death worldwide, resulting in approx. 10 million deaths annually. Many synthetic anticancer drugs are available, but they often come with side effects and can interact negatively with other medications. Additionally, many chemotherapy drugs used for cancer treatment can develop resistance and harm normal cells, leading to dose-limiting side effects. As a result, finding effective cancer treatments and developing new drugs remains a significant challenge. However, plants are a potent source of natural products with the potential for cancer treatment. These biologically active compounds may be the basis for enhanced or less toxic derivatives. Herbal medicines/phytomedicines, or plant-based drugs, are becoming more popular in treating complicated diseases like cancer due to their effectiveness and are a particularly attractive option due to their affordability, availability, and lack of serious side effects. They have broad applicability and therapeutic efficacy, which has spurred scientific research into their potential as anticancer agents. This review focuses on Paclitaxel (PTX), a plant-based drug derived from Taxus sp., and its ability to treat specific tumors. PTX and its derivatives are effective against various cancer cell lines. Researchers can use this detailed information to develop effective and affordable treatments for cancer.

Engineering of surface-modified CuBTC-MXene nanocarrier for adsorption and co-loading of curcumin/paclitaxel from aqueous solutions for synergistic multi-therapy of cancer.

Two-dimensional (2D) nanomaterials can improve drug delivery by reducing toxicity, increasing bioavailability and boosting efficacy. In this study, the simultaneous use of transition metal carbides and nitrides (MXenes) along with copper (II) benzene-1, 3, 5-tricarboxylate metal-organic framework (Cu - BTC/MOF) as attractive nanocarriers are investigated for loading and delivering curcumin (CUR) and paclitaxel (PTX) drugs to cancer cells. The efficiency of surface termination (bare and oxygen) in the adsorption of PTX and CUR drugs and the co-loading of these two drugs are evaluated. Our results show that the strongest interaction energy belongs to the adsorption of drug CUR on the MXNNO-Cu-BTC adsorbent, while the interaction of PTX drug with the MXNO- Cu-BTC in the MXNO-Cu-BTC/PTX&CUR system is the lowest due to the particular structure of the drug and the adsorbent. Our results show that at the beginning simulation, the interaction energy between the PTX drug and water in PTX/MXN system is -4645.48 kJ/mol, which reduces to -3848.71 kJ/mol after the system reaches equilibrium. Therefore, the inspected adsorbents have a good performance in adsorbing CUR and PTX drugs. The obtained results from this investigation provide valuable information about experimental studies by medical scientists in the future.Communicated by Ramaswamy H. Sarma.

Coating with cationic inulin enhances the drug release profile and in vitro anticancer activity of lecithin-based nano drug delivery systems.

Core-shell structured lipidic nanoparticles (LNPs) were developed using lecithin sodium acetate (Lec-OAc) ionic complex as a core unit and quaternized inulin (QIn) as the shell part. Inulin (In) was modified using glycidyl trimethyl ammonium chloride (GTMAC) as a positively charged shell part and used for coating the negatively surface charged Lec-OAc. The critical micelle concentration (CMC) of the core was determined as 1.047 × 10-4 M, which is expected to provide high stability in blood circulation as a drug-carrying compartment. The amounts of curcumin (Cur) and paclitaxel (Ptx) loaded to LNPs (CurPtx-LNPs), and quaternized inulin-coated LNPs (Cur-Ptx-QIn-LNPs) were optimized to obtain mono-dispersed particles with maximum payload. The total amount of 2.0 mg of the drug mixture (1 mg Cur and 1 mg Ptx) was the optimized quantity for QIn-LNPs and CurPtx-QIn-LNPs due to the favorable physicochemical properties determined by dynamic light scattering (DLS) studies. This inference was confirmed by differential scanning calorimeter (DSC), and Fourier-transform infrared (FT-IR). SEM and TEM images clearly revealed the spherical shapes of LNPs and QIn-LNPs, and QIn covered the LNPs completely. The cumulative release measurements of Cur and Ptx from CurPtx-QIn-LNPs, along with the kinetic studies, showed a significant decrease in the release period of drug molecules with the effect of the coating. At the same time, Korsmeyer-Peppas was the best diffusion-controlled release model. Coating of the LNPs with QIn increased the cell-internalization of NPs to the MDA-MB-231 breast cancer cell lines, resulting in a better toxicity profile than the empty LNPs.

Targeted delivery of paclitaxel drug using polymer-coated magnetic nanoparticles for fibrosarcoma therapy: in vitro and in vivo studies.

Fibrosarcoma is a rare type of cancer that affects cells known as fibroblasts that are malignant, locally recurring, and spreading tumor in fibrous tissue. In this work, an iron plate immersed in an aqueous solution of double added deionized water, supplemented with potassium permanganate solution (KMnO4) was carried out by the pulsed laser ablation in liquid method (PLAIL). Superparamagnetic iron oxide nanoparticles (SPIONs) were synthesized using different laser wavelengths (1064, 532, and 266 nm) at a fluence of 28 J/cm2 with 100 shots of the iron plate to control the concentration, shape and size of the prepared high-stability SPIONs. The drug nanocarrier was synthesized by coating SPION with paclitaxel (PTX)-loaded chitosan (Cs) and polyethylene glycol (PEG). This nanosystem was functionalized by receptors that target folate (FA). The physiochemical characteristics of SPION@Cs-PTX-PEG-FA nanoparticles were evaluated and confirmed by Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-Ray diffraction (XRD), atomic force microscopy (AFM), and dynamic light scattering (DLS) methods. Cell internalization, cytotoxicity assay (MTT), apoptosis induction, and gene expression of SPION@Cs-PTX-PEG-FA were estimated in fibrosarcoma cell lines, respectively. In vivo studies used BALB/c tumor-bearing mice. The results showed that SPION@Cs-PTX-PEG-FA exhibited suitable physical stability, spherical shape, desirable size, and charge. SPION@Cs-PTX-PEG-FA inhibited proliferation and induced apoptosis of cancer cells (P < 0.01). The results of the in vivo study showed that SPION@Cs-PTX-PEG-FA significantly decreased tumor size compared to free PTX and control samples (P < 0.05), leading to longer survival, significantly increased splenocyte proliferation and IFN-γ level, and significantly decreased the level of IL-4. All of these findings indicated the potential of SPION@Cs-PTX-PEG-FA as an antitumor therapeutic agent.

Preparation of Paclitaxel-Encapsulated Bio-Functionalized Selenium Nanoparticles and Evaluation of Their Efficacy against Cervical Cancer.

The potentiality of nanomedicine in the cancer treatment being widely recognized in the recent years. In the present investigation, the synergistic effects of chitosan-modified selenium nanoparticles loaded with paclitaxel (PTX-chit-SeNPs) were studied. These selenium nanoparticles were tested for drug release analysis at a pH of 7.4 and 5.5, and further characterized using FTIR, DLS, zeta potential, and TEM to confirm their morphology, and the encapsulation of the drug was carried out using UPLC analysis. Quantitative evaluation of anti-cancer properties was performed via MTT analysis, apoptosis, gene expression analysis, cell cycle arrest, and over-production of ROS. The unique combination of phytochemicals from the seed extract, chitosan, paclitaxel, and selenium nanoparticles can be effectively utilized to combat cancerous cells. The production of the nanosystem has been demonstrated to be cost-effective and have unique characteristics, and can be utilized for improving future diagnostic approaches.

Animal protein-plant protein composite nanospheres for dual-drug loading and synergistic cancer therapy.

The co-delivery of multiple drugs using one drug carrier is a viable strategy to optimize drug dosage and reduce the side effects in chemotherapy. Herein, a hydrophilic animal protein (silk fibroin) and a hydrophobic plant protein (zein) were selected for preparing a composite drug carrier. Adapting our previously developed method for the preparation of regenerated silk fibroin (RSF) nanospheres, we prepared RSF/zein nanospheres that displayed an interesting structure including a single central hole. The particle size of the RSF/zein nanospheres was regulated from 150 to 460 nm by varying the preparation conditions, implying that such a drug carrier is suitable for both intravenous administration and lymphatic chemotherapy. Two anti-cancer drugs with different target sites, paclitaxel (PTX) and curcumin (CUR), were selected for the preparation of dual-drug-loaded CUR/PTX@RSF/zein nanospheres. Both drugs achieved a high loading capacity in the RSF/zein nanospheres, i.e., 8.2% for PTX and 12.1% for CUR. Subsequently, the encapsulated PTX and CUR were released from the RSF/zein nanospheres in a sustained manner for at least 7 days. Importantly, these dual-drug-loaded RSF/zein nanospheres exhibited a considerable synergistic therapeutic effect, showing more efficient suppression of in vitro cancer cell growth than free PTX or CUR, a combination of free PTX and CUR, or single-drug-loaded nanospheres. Therefore, the CUR/PTX@RSF/zein nanospheres developed in this study hold great potential for combination chemotherapy in future clinical applications.

Interface-Engineered Paclitaxel-Based Hollow Mesoporous Organosilica Nanoplatforms for Photothermal-Enhanced Chemotherapy of Tumor.

Having benefited from the combination of different therapeutic modalities, functionalized nanoplatforms with synergistic strategies have aroused great interest in anticancer treatment. Herein, an engineered, a biodegradable hollow mesoporous organosilica nanoparticle (HMON)-based nanoplatform was fabricated for photothermal-enhanced chemotherapy of tumor. For the first time, we demonstrated that HMONs could serve as nanocarriers for co-delivering of both the paclitaxel and photothermal agent new indocyanine green (IR820), denoted as Paclitaxel/IR820@ HMONs-PEG. The as-prepared nanosystem exhibited a high paclitaxel-loading capacity of 28.4%, much higher than most paclitaxel-loaded nanoformulations. Furthermore, incorporating thioether bonds (S-S) into the HMONs' framework endowed them with GSH-responsive biodegradation behavior, leading to the controllable release of drugs under a tumor reducing microenvironment, and hindered the premature release of paclitaxel. Upon being irradiated with an NIR laser, the obtained co-delivery nanosystem exhibited great photothermal properties generated from IR820. The fabricated nanocomposites could significantly suppress tumor growth under NIR laser irradiation, as validated by in vitro and in vivo assessments. Combined with outstanding biocompatibility, the constructed nanosystem holds great potential in combinational antitumor therapy.

Paclitaxel: Application in Modern Oncology and Nanomedicine-Based Cancer Therapy.

Paclitaxel is a broad-spectrum anticancer compound, which was derived mainly from a medicinal plant, in particular, from the bark of the yew tree Taxus brevifolia Nutt. It is a representative of a class of diterpene taxanes, which are nowadays used as the most common chemotherapeutic agent against many forms of cancer. It possesses scientifically proven anticancer activity against, e.g., ovarian, lung, and breast cancers. The application of this compound is difficult because of limited solubility, recrystalization upon dilution, and cosolvent-induced toxicity. In these cases, nanotechnology and nanoparticles provide certain advantages such as increased drug half-life, lowered toxicity, and specific and selective delivery over free drugs. Nanodrugs possess the capability to buildup in the tissue which might be linked to enhanced permeability and retention as well as enhanced antitumour influence possessing minimal toxicity in normal tissues. This article presents information about paclitaxel, its chemical structure, formulations, mechanism of action, and toxicity. Attention is drawn on nanotechnology, the usefulness of nanoparticles containing paclitaxel, its opportunities, and also future perspective. This review article is aimed at summarizing the current state of continuous pharmaceutical development and employment of nanotechnology in the enhancement of the pharmacokinetic and pharmacodynamic features of paclitaxel as a chemotherapeutic agent.

Pharmacokinetics, plasma protein binding, and metabolism of a potential natural chemosensitizer from Marsdenia tenacissima in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Marsdenia tenacissima (Roxb.) Wight et Arn is a medicinal plant mainly distributed in southwest China. It is used in folk medicine for the treatment of tumors and is synergistic with chemotherapies. In our previous study, 11α-O-2-methybutyryl-12ß-O-tigloyl-tenacigenin B (MT2), a main steroid aglycone isolated from the total aglycones of M. tenacissima, significantly enhanced the in vivo antitumor effect of paclitaxel in mice bearing human tumor xenografts, showing its potential as a chemosensitizer. However, the pharmacokinetic characteristics, plasma protein binding rate, and metabolic profile of MT2 remain unclear. AIM OF THE STUDY: To elucidate the pharmacokinetic characteristics, plasma protein binding rate, and metabolic profile of MT2 in rats. MATERIALS AND METHODS: MT2 in rat plasma and phosphate-buffered saline was quantified using ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method, while the MT2 metabolites in rat liver microsomes were analyzed using UPLC-triple time-of-flight MS/MS. RESULTS: For intravenously administered MT2, the maximum plasma concentration and the area under the plasma concentration-time curve indicated dose dependency, while the elimination half-life time, the mean residence time, apparent volume of distribution and total apparent clearance values remained relatively unchanged in both the 5 mg/kg and 10 mg/kg groups. For orally administered MT2, the bioavailability was 1.08-1.11%. In rat plasma, MT2 exhibited a protein binding rate of 93.84-94.96%. In rat liver microsomes, MT2 was metabolized by oxidation alone or in combination with demethylation, and five MT2 metabolites were identified. CONCLUSION: MT2 has low oral bioavailability and a high plasma protein binding rate in rats. After administration, MT2 is transformed into oxidative metabolites in the liver. To achieve a high blood concentration of MT2, it should be administered intravenously. These findings would serve as a reference for further MT2-based pharmacological study and drug development.

Identification and in-silico characterization of taxadien-5α-ol-O-acetyltransferase (TDAT) gene in Corylus avellana L.

Paclitaxel® (PC) is one of the most effective and profitable anti-cancer drugs. The most promising sources of this compound are natural materials such as tissue cultures of Taxus species and, more recently, hazelnut (Corylus avellana L.). A large part of the PC biosynthetic pathway in the yew tree and a few steps in the hazelnut have been identified. Since understanding the biosynthetic pathway of plant-based medicinal metabolites is an effective step toward their development and engineering, this paper aimed to identify taxadiene-5α-ol-O-acetyltransferase (TDAT) in hazelnut. TDAT is one of the key genes involved in the third step of the PC biosynthetic pathway. In this study, the TDAT gene was isolated using the nested-PCR method and then characterized. The cotyledon-derived cell mass induced with 150 µM of methyl jasmonate (MeJA) was utilized to isolate RNA and synthesize the first-strand cDNA. The full-length cDNA of TDAT is 1423 bp long and contains a 1302 bp ORF encoding 433 amino acids. The phylogenetic analysis of this gene revealed high homology with its ortholog genes in Quercus suber and Juglans regia. Bioinformatics analyses were used to predict the secondary and tertiary structures of the protein. Due to the lack of signal peptide, protein structure prediction suggested that this protein may operate at the cytoplasm. The homologous superfamily of the T5AT protein, encoded by TDAT, has two domains. The highest and lowest hydrophobicity of amino acids were found in proline 142 and lysine 56, respectively. T5AT protein fragment had 24 hydrophobic regions. The tertiary structure of this protein was designed using Modeler software (V.9.20), and its structure was verified based on the results of the Verify3D (89.46%) and ERRAT (90.3061) programs. The T5AT enzyme belongs to the superfamily of the transferase, and the amino acids histidine 164, cysteine 165, leucine 166, histidine 167, and Aspartic acid 168 resided at its active site. More characteristics of TDAT, which would aid PC engineering programs and maximize its production in hazelnut, were discussed.

Merocyanine-paclitaxel conjugates for photothermal induced chemotherapy.

Small molecular nanomedicines that integrate the flexibility of self-assembly strategies and the advantages of a precise molecular structure, a high drug content and controlled drug release are effective diagnostic and therapeutic modalities. Herein, merocyanine-paclitaxel conjugates (MC-PTX) were developed and fabricated by using the degradable ester bonds as the linker. The as-prepared MC-PTX could self-assemble into nanoparticles (MC-PTX NPs) using the non-covalent molecular interaction via the nanoprecipitation method. MC-PTX NPs possess a favorable biological stability and can efficiently release the paclitaxel (PTX) activated by the heat of the photoactive material merocyanine under light illumination, as monitored using dynamic light scattering. The obtained MC-PTX NPs could be endocytosed into cancer cells and release PTX under laser irradiation in the cytoplasm, thus eliciting a satisfactory anticancer effect. Photothermal triggered degradation upon light illumination could enhance the chemotherapeutic efficacy of paclitaxel. The fluorescent nature of the NPs could visualize the internalization process. We believe that this robust nanomedicine offers a novel strategy to facilitate clinical translation for use as a small molecular chemotherapy nanomedicine.

A directed co-assembly of herbal small molecules into carrier-free nanodrugs for enhanced synergistic antitumor efficacy.

Carrier-free nanomedicines without structural modification are attractive for the development of natural small molecules (NSMs) and biomedical applications. Moreover, the combination of NSMs is expected to obtain nanomedicines with high efficacy and low side effects due to their inherent pharmacological activities and health benefits. However, poor water solubility and low bioavailability of NSMs limit their wider biomedical and clinical applications. In this study, we revealed the co-assembly properties of pentacyclic triterpenoids and constructed a series of carrier-free nanodrugs, which are co-assembled nanoparticles (NPs) formed by the combination of two NSMs via a supramolecular assembly strategy. Experimental work and simulation studies were combined to reveal the co-assembly mechanism of non-covalent interactions between NSMs. Not only do co-assembled NPs have rapid cellular uptake ability and passive targeting tumor ability based on the EPR effect, but also their constituent units could arrest the cell cycle at different stages of tumor cells and induce apoptosis, showing synergistic anti-tumor effects (CI < 0.7). Compared with self-assembled NPs and positive control, co-assembled NPs show the strongest therapeutic effect in vivo. Importantly, the co-assembled NPs highlight the unique advantages of NSMs in terms of biosafety and health benefits, and systemic toxicity and histological examination confirm that co-assembled NPs have reliable biosafety, and no side effects and nano toxicity risks were observed.

Pathways Related to the Anti-Cancer Effects of Metabolites Derived from Cerrado Biome Native Plants: An Update and Bioinformatics Analysis on Oral Squamous Cell Carcinoma.

BACKGROUND: Oral cancer is a significant health problem worldwide. Oral squamous cell carcinoma (OSCC) is a malignant neoplasm of epithelial cells that mostly affects different anatomical sites in the head and neck and derives from the squamous epithelium or displays similar morphological characteristics. Generally, OSCC is often the end stage of several changes in the stratified squamous epithelium, which begin as epithelial dysplasia and progress by breaking the basement membrane and invading adjacent tissues. Several plant-based drugs with potent anti-cancer effects are considered inexpensive treatments with limited side effects for cancer and other diseases. OBJECTIVE: The aim of this review is to explore whether some Brazilian plant extracts or constituents exhibit anti-tumorigenic activity or have a cytotoxic effect on human oral carcinoma cells. METHODS: Briefly, OSCC and several metabolites derived from Brazilian plants (i.e., flavonoids, vinblastine, irinotecan, etoposide and paclitaxel) were used as keywords to search the literature on PubMed, GenBank and GeneCards. RESULTS: The results showed that these five chemical compounds found in Cerrado Biome plants exhibit anti-neoplastic effects. Evaluating the compounds revealed that they play a main role in the regulation of cell proliferation. CONCLUSION: Preserving and utilising the biodiversity of our planet, especially in unique ecosystems, such as the Cerrado Biome, may prove essential to preserving and promoting human health in modern contexts.

Biotechnological approaches to the production of plant-derived promising anticancer agents: An update and overview.

The plant kingdom is a rich source of bioactive compounds, many of which have been used since pre-history for their therapeutic properties to treat a range of illnesses. These metabolites have recently attracted attention to their antineoplastic activities to treat various cancers relying on different mechanisms. Some of these molecules are glycosides, which have proven useful as anti-cancer agents, namely podophyllotoxin (PPT) anaryltetralin lignan or alkaloids. There are three primary forms of alkaloids, such as indole alkaloids (vincristine and vinblastine from Catharanthus roseus), quinoline alkaloid (camptothecin from Camptotheca acuminata), and diterpenoid alkaloid (taxol and it's analogous from Taxus and Corylus species). This review considers various plant biotechnology approaches used to enhance the production of these anticancer molecules in different species. In this regard, many in vitro culture techniques such as stimulation of suspension culture and hairy roots are being used to investigate the effects of plant growth regulators and elicitors on various explants.

PEGylated-Paclitaxel and Dihydroartemisinin Nanoparticles for Simultaneously Delivering Paclitaxel and Dihydroartemisinin to Colorectal Cancer.

PURPOSE: Development of a nanoplatform constructed by the PEG-dual drug conjugation for co-delivery of paclitaxel (PTX) and Dihydroartemisinin (DHA) to the tumor. METHODS: PEG was conjugated with PTX and DHA to form PTX-PEG-DHA complex as a nanocarrier. The PTX and DHA were co-encapsulated in PTX-PEG-DHA nanoparticles (PD@PPD NPs) by the emulsion evaporation method. The physicochemical properties of PD@PPD Nps were characterized, including size, zeta potential, and morphology. The drug loading capacity and entrapment efficiency, in vitro drug release at different pH conditions were also evaluated. For in vitro assessment, the effects of the NPs on HT-29 colorectal cancer cells, including intracellular uptake, cytotoxicity, and Bcl-2 protein expression were assessed. The in vivo distribution of the NPs was investigated by labelling the NPs with Cyanine 5.5 fluorophore. Finally, the antitumor efficacy of the NPs was evaluated in HT-29 tumor-bearing mice. RESULTS: The nanoparticles were formed at small size (~114 nm) and narrow distribution. The combination of PTX and DHA in the DHA-PEG-PTX nanosystems (PD@PPD) showed remarkably increased apoptosis in colorectal adenocarcinoma HT-29 cells, as compared to free drug treatment. More importantly, the PD@PPD nanoparticles exhibited significantly higher accumulation in the tumor site owing to the enhanced permeability and retention (EPR) effect, effectively restrained the tumor growth in vivo at low-dose of PTX while reducing the systemic toxicity. CONCLUSIONS: The combination of PTX and DHA in a PEG-conjugated dual-drug co-delivery system can minimize the severe side effect associated with the high-dose of PTX while enhancing the antitumor efficacy.

Platelet-derived nanomotor coated balloon for atherosclerosis combination therapy.

Atherosclerosis can lead to thrombosis, blood supply disorders, and even serious consequences such as lumen occlusion or wall rupture and bleeding, so it is urgent to develop an effective comprehensive therapy. Here, a novel kind of drug-coated balloon, where drug-loaded porous nanomotors with autonomous motion ability are used as the coating of the balloon, is reported. The drug-loaded porous nanomotors based on Janus aminated mesoporous silica (JAMS) that was obtained by asymmetric modification of platinum (Pt) nanoparticles are prepared and characterized. The platelet membrane is used to wrap the nanomotors to reduce the leakage of drugs before reaching the plaque. The motion ability of the nanomotor under the irradiation of near-infrared light, the sustained release behavior and effect of the loaded drugs (anti-proliferative drug paclitaxel and the anti-vascular cell adhesion molecule-1 antibody) are investigated in detail. The biomimetic effect and encapsulation effect on drug loading of the platelet membrane, and the elimination of inflammatory macrophages under the photothermal effect produced by Pt are also characterized. The results indicate that the drug-loaded porous nanomotors proposed for drug balloon coating in this work can penetrate into the plaque and enhance the drug retention efficiency, realizing short-term photothermal elimination of inflammatory macrophages and long-term anti-proliferation effect of the drug, providing a possible choice for drug balloon coating with high efficiency in the treatment of atherosclerosis.

Two-Phase Synthesis of Taxol.

Taxol (a brand name for paclitaxel) is widely regarded as among the most famed natural isolates ever discovered, and has been the subject of innumerable studies in both basic and applied science. Its documented success as an anticancer agent, coupled with early concerns over supply, stimulated a furious worldwide effort from chemists to provide a solution for its preparation through total synthesis. Those pioneering studies proved the feasibility of retrosynthetically guided access to synthetic Taxol, albeit in minute quantities and with enormous effort. In practice, all medicinal chemistry efforts and eventual commercialization have relied upon natural (plant material) or biosynthetically derived (synthetic biology) supplies. Here we show how a complementary divergent synthetic approach that is holistically patterned off of biosynthetic machinery for terpene synthesis can be used to arrive at Taxol.

The Effect of Bitter Melon (Momordica charantia) Extract on the Uptake of 99mTc Labeled Paclitaxel: In Vitro Monitoring in Breast Cancer Cells.

BACKGROUND: Bitter Melon Extract (BME) is widely used for the treatment of various diseases worldwide due to its rich phytochemical and antioxidant content. The well-known anti-cancer drug Paclitaxel (PAC) plays a major role in the treatment of various cancer types such as ovarian, breast, and lung cancer. Technetium-99m (99mTc) radiolabeled paclitaxel is emerging as an imaging probe for breast cancer in vivo. 99mTc labeled compounds have been attracting more scientific attention since the achievement of earlier researches in Nuclear Medicine. People consume several types of diets of plant origin without knowing the interaction with radiolabeled compounds or radiopharmaceuticals. Objective: In the current study, we aimed to monitor the potential effects of the BME on the uptake of 99mTc labeled Paclitaxel (99mTc-PAC) against MCF-7 (ER+) and MDA-MB-231 (ER-) cell lines by using in vitro methods. METHODS: BME was obtained by the extraction of BM seeds by 80% ethanol. PAC was labeled with 99mTc by stannous chloride (SnCl2) as a reducing agent. Cytotoxicity and incorporation assays were performed on MCF-7 and MDA-MB-231 cells within the cell culture studies. RESULTS: The uptake value of 99mTc-PAC on MCF-7 cells at 240 minutes was 6.20% and BME treated 99mTc- PAC value was 17.39%. Conclusion: It is observed that BME treatment has a significant effect on the uptake of 99mTc-PAC on MCF-7 cells which is a known estrogen receptor-positive breast carcinoma cell line. It is concluded that this effect could be due to the estrogen receptor-dependent interaction of BME.

Lipid-PLGA hybrid nanoparticles of paclitaxel: Preparation, characterization, in vitro and in vivo evaluation.

Paclitaxel loaded lipid-polymer nanoparticles (NPs) were successfully synthesized using poly lactide-co-glycolide (PLGA) as polymer and stearyl amine, soya lecithin as lipids via single step nanoprecipitation method. The study was aimed to combine the advantage of structural integrity of hybrid NPs containing PLGA core and lipid in the shell. Surfactants such as polyvinyl alcohol (PVA), tocopheryl polyethylene glycol succinate (TPGS), pluronic 68 (F68) and human serum albumin (HSA) were used as stabilizers. NPs were characterized w.r.t. morphology, particle size, zeta potential, encapsulation efficiency, in vitro drug release, protein binding capability and blood compatibility. NPs were in size range of 150-400 nm and the particle size was greatly influenced by type and concentration of surfactants and lipids. TEM analysis confirmed the spherical shape and coating of the lipid on the NPs surface. Highest percentage entrapment efficiency was observed in NPs prepared with HSA as surfactant. The release rate of paclitaxel from modified NPs was much slower as compared to unmodified NPs. The percent protein binding of P-PVA, P-TPGS, P-F68 and P-HSA (unmodified NPs) was found to be 15.11%, 16.27%, 27.90% and 33.72%, respectively demonstrating effect of surface properties of NPs on protein binding. The hemolytic activity of the NPs was found to be dependent on type of surfactant and not on the lipid employed. PVA, TPGS, F68, HSA surfactants showed ~16%, ~10%, ~13%, ~7% hemolysis rate, respectively. The surface nature of NPs had a significant effect on the circulation profile of formulations. The HSA based NPs showed prolonged blood circulation time when compared to NPs without lipid coating. Thus, the synthesized dual lipid coated PLGA NPs with HSA could act as a potential nano-system for controlled delivery of paclitaxel.