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For the purpose of clinical intravenous injection of 10-hydroxycamptothecin, a novel formulation of lipid nanoparticles loaded with 10-hydroxycamptothecin-phospholipid complex (HCPT-PC-LNs) was prepared by solvent evaporation and high-pressure homogenization methods. Spherical particles with a mean particle size of 200 nm and high encapsulation eff...
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Citations
... Furthermore, Phytosome® technology (Khan et al., 2013) involved the complexation of water soluble constituents with phospholipids into innovative, submicron lipid vesicles (Kidd, 2009, Freag et al., 2013 to improve their bioavailability. It was revealed that, phytosomes substantially improved the bioavailability, enhanced the efficacy, and reduced the toxic side effects of: daidzein (Zhang et al., 2011), rutin (Singh et al., 2012), 10 hydroxycamptothecin (Wei et al., 2010), oxymatrine (Yue et al., 2010), curcumin (Allam et al., 2015), icariin (Alhakamy et al., 2020a) thymoquinone (Alhakamy et al., 2020b) and luteolin (Elnaggar et al., 2018). Moreover, phospholipid complexation with various peptides and proteins including; salmon calcitonin (Sang Yoo and Gwan Park, 2004), lysozyme (Yoo et al., 2001) and insulin (Cui et al., 2006, Peng et al., 2012 was employed to improve their liposolubility, enhance their loading efficiency and thus, their therapeutic effect. ...
PEGylated Liquisomes (P-Liquisomes), a novel drug delivery system was designed for the first time by incorporating phospholipid complex in PEGylated liquid crystalline nanoparticles (P-LCNPs). L-carnosine (CN), a challenging dipeptide, has proven to be a promising anti-cancer drug. However, it exhibits high water solubility and extensive in-vivo degradation that halts its use. The objective of this work was to investigate the ability of our novel system to improve the CN anticancer activity by prolonging it’s release and protecting it in-vivo. In-vitro appraisal revealed spherical light-colored vesicles encapsulated in the liquid crystals, confirming the successful formation of the combined system. P-Liquisomes were nano-sized (149.3 ± 1.4 nm), with high ZP (-40.2 ± 1.5 mV), complexation efficiency (97.5 ± 0.9 %) and outstanding sustained release of only 75.4 % released after 24 h, compared to P-LCNPs and Phytosomes. The results obtained with P-Liquisomes are considered as a break through compared to P-LCNPs or Phytosomes alone, especially when dealing with the hydrophilic CN. In-vitro cytotoxicity evaluation, revealed superior cytotoxic effect of P-Liquisomes (IC50 = 25.9) after 24 h incubation. Besides, P-Liquisomes proved to be non-toxic in-vivo and succeeded to show superior chemopreventive activity manifested by reduction of; % tumor growth (7.1%), VEGF levels (14.3 pg/g tissue), cyclin D1 levels 15.5 ng/g tissue and elevation in caspase-3 level (36.4 ng/g tissue), compared to Phytosomes and CN solution. Conclusively, P-Liquisomes succeded to achieve the maximum therapeutic outcome of CN without altering its activity and might be used as a sustained delivery system for other promising hydrophilic compounds.
... Camptothecin (CPT) is a natural camptotheca alkaloid which exhibits a wide range of anti-cancer activities [143]. Several CPT derivatives like hydroxycamptothecin (HCPT) [144], 9-Nitrocamptotecin (9-NC) [145], 7-ethyl-10-hydroxy camptothecin (SN38) [146], and 10-hydroxycamptothecin phospholipid complex have been synthesized to ensure greater clinical efficacy and decreased toxicity [147]. ...
... Mannitol is a water-soluble polysaccharide and serves as a carrier in the mixture of mannitol with CPT NPs to shape hydrogen bonds with CPT, thus resulting in increased solubility of CPT and drug accumulation in the tumor site [107,143]. Moreover, nanocarriers with higher drug concentration were developed by combining HCPT with multi-walled carbon nanotube (MWCNT), which demonstrated 16% higher drugloading capacity with increased cellular uptake and blood circulation [107]. ...
Introduction: Cancer has always been a menace to society. Hepatocellular carcinoma (HCC) is one of the most lethal and 3rd largest causes of deaths around the world. HCC has shown a high mortality rate due to multidrug resistance, late diagnosis, high side-effects associated with chemotherapy, and the chance of tumor recurrence.
Area covered: The emergence of natural actives is considered the greatest boon for fighting cancer. The natural actives take precedence over the traditional chemotherapeutic drugs in terms of their multi-target, multi-level and coordinated effects in the treatment of HCC. Literature reports indicate the tremendous potential of bioactive natural products in inhibiting the HCC via molecular drug targeting, augmented bioavailability, and the ability for both passive or active targeting and stimulus-responsive drug release characteristics. This review provides an overview of the various factors responsible for causing HCC along with newer treatment approaches involved in the mechanism of action of different natural actives used for the HCC treatment via different molecular pathways. Besides, the promising advantage of natural bioactive-loaded nanocarriers in HCC treatment has also been also presented in this review.
Expert opinion: The remarkable outcomes have been observed with the therapeutic efficacy of the nanocarriers of natural actives in the treatment of HCC. Furthermore, it requires a thorough assessment of the safety and efficacy evaluation of the nanocarriers for the delivery of targeted natural active ingredients in HCC.
... Additionally, the concentration of the two HCPT-loaded micelle formulations in the liver was much higher than that of HCPT injection at all time points, which may be attributed to the particle size of the two micelles and the deoxycholic acid in the two polymer carriers. First, it has been proved that nanoparticles with a diameter of more than 200 nm are easily accumulated in the liver, while those with a particle size of <200 nm go more to the spleen (Shi et al., 2005;Wei et al., 2010). Secondly, it is believed that deoxycholic acid has liver targeting so that the two micelles accumulate in the liver (Chen et al., 2012;Chen et al., 2010;Parks et al., 1999;Putz et al., 2005), which may show a significant advantage in the treatment of liver cancer in situ . ...
Tumor multidrug resistance (MDR) is one of the main reasons for the failure of clinical chemotherapy. Here, a bio-responsive anti-drug-resistant polymer micelle that can respond to the reductive GSH in the tumor microenvironment (TME) for delivery of HCPT was designed. A new type of with anti-drug resistance and anti-tumor effect was synthesized and used to encapsulated HCPT to form reduction-sensitive micelles (PDSAH) by a thin-film dispersion method. It is demonstrated that the micelle formulation improves the anti-tumor activity and biosafety of HCPT, and also plays a significant role in reversing the drug resistance, which contributes to inhibiting the tumor growth and prolonging the survival time of H22 tumor-bearing mice. The results indicate that this nanoplatform can serve as a flexible and powerful system for delivery of other drugs that are tolerated by tumors or bacteria.
... It is found that the release curve of CPFX in Figure 10 conforms to the Ritger−Peppas model of Qt = Kt n , as shown in Table 2. According to some literatures [30,31], the mechanism of drug-release was drug diffusion, when n ≤ 0.45. When 0.45 < n < 0.89, the drug diffusion and the dissolution of drug carrier have a synergistic effect on the release rate of drug. ...
Polylactic acid (PLA) surgical suture can be absorbed by human body. In order to avoid surgical site infections (SSIs), the drug is usually loaded on the PLA suture, and then the drug can release directly to the wound. Because the different types of wounds heal at different times, it is needed to control the drug release rate of PLA suture to consistent to the wound healing time. Two biopolymers, polyglycolide (PGA) and polycaprolactone (PCL), were selected as the carrier of ciprofloxacin (CPFX) drug, and then the CPFX-PCL/PGA was coated on the PLA suture. The degradation rate of drug-carrier can be controlled by adjusting the proportion of PCL/PGA, which can regulate the rate of CPFX drug release from PLA suture. The results show that the surface of PLA suture, coating with PCL/PGA, was very rough, which led to increased stitching resistance when we were suturing the wound. These materials, such as the PLA suture, the PCL/PGA carriers and the CPFX drug, were just physically mixed rather than chemically reacted, which was very useful for ensuring the original efficacy of CPFX drug. With the increasing of PCL in the carriers, both the breaking strength and elongation of these un-degraded sutures increased. During degradation, the breaking strength of all sutures gradually decreased, and the more PCL in the coating materials, the longer effective strength-time for the suture. With the increasing of PCL in the drug-carrier, the rate of drug releasing became lower. The drug release mechanism of CPFX-PCL/PGA was a synergistic effect of drug diffusion and PCL/PGA carrier dissolution.
... cyclodextrin complex and nanosponge ( Devasari et al., 2015;Dora et al., 2016), reverse micelle loaded lipid nanocarriers ( Vrignaud et al., 2012), Poly (D,L-lactic-co-glycolic acid) nanoparticles ( Marslin et al., 2009), liposome, chitosan nanoparticles ( Srinivasan and Shoyele, 2014), Poly caprolactone-polyethylene glycol-polycaprolactone (PCEC) nanoparticle ( Barghi et al., 2014), core-shell type lipid-polymer hybrid nanoparticle ( Mandal et al., 2016) and others. The skill of complexing therapeutic active constituents with phospholipids has been popularising for improving bioavailability and therapeutic efficacy of a number of poorly absorbed constituents ( Hüsch et al., 2011;Jena et al., 2014;Maiti et al., 2007;Wei et al., 2010;Yanyu et al., 2006). Phospholipids are amphipathic molecules with appreciable solubility in aqueous and non-aqueous mediums. ...
The current study was aimed to prepare a molecular complex of erlotinib (ERL) with phospholipid (PC) for enhancement of solubility and thus bioavailability, therapeutic efficacy and reducing the toxicity of erlotinib. Phospholipid complex of drug was prepared by solvent evaporation method and characterized by differential scanning calorimetry (DSC), Fourier transform infra-red spectroscopy (FT-IR), proton and phosphorus nuclear magnetic resonance spectroscopy ((1)H NMR and (31)P NMR), powder X-ray diffraction (P-XRD), scanning electron microscopy (SEM) and transmission electron microscopy (TEM), which all explained the interactions of two components, validating the complexation phenomenon. In silico study also supported the phase change and molecular interactions for the establishment of ERL-PC. Spherical shaped nanostructures with 183.37±28.61nm size, -19.52±6.94mV potential and 28.59±2.66% loading efficiency were formed following dispersion of ERL-PC in aqueous media. In vitro release study revealed the higher release of ERL-PC due to amorphization and solubilization of drug. Caco-2 cell uptake resulted in ∼2 fold higher uptake of ERL-PC than free drug. In vitro cell culture studies were performed using human pancreatic adenocarcinoma cell lines, which demonstrated the higher cytotoxicity and apoptosis in case of ERL-PC. In vivo pharmacokinetics also supported the in vitro observations and showed ∼1.7 fold higher bioavailability with ERL-PC than ERL. Finally, In vivo efficacy and toxicity studies explained the superiority of ERL-PC over the free drug. Based on the results, phospholipid complex appears to be a promising tool to enhance bioavailability, efficacy, cytotoxicity and safety of erlotinib.
... Such a unique mechanism makes it difficult for HCPT to form cross tolerance with other antineoplastic drugs. Thus, it may form part of a combination treatment with a number of medicines for clinical uses (11). The primary negative effects include myelosuppression and a gastrointestinal reaction. ...
In order to evaluate the anticancer effect of 10‑hydroxycamptothecin (HCPT) in terms of inducing the apoptosis of human osteosarcoma cells, its apoptosis-inducing molecular mechanisms were investigated. In the present study, the anticancer effects of HCPT were revealed to result in suppressed cell viability, increased cytotoxicity, the induction of apoptosis and an augmented apoptotic nucleolus of human osteosarcoma cells. MG-63 cells were cultured with HCPT (0, 20, 40 and 80 nM) for 24 and 48 h. An MTT assay and a lactate dehydrogenase assay were used to analyze the anticancer effect of HCPT on cell viability and cytotoxicity in MG-63 cells. MG-63 cell apoptosis, and caspase-9 and caspase-3 activity levels were evaluated using flow cytometry and an ELISA. Western blot analysis was used to detect the protein expression levels of p53, poly (ADP-ribose) polymerase-1 (PARP-1), cytochrome c and B cell lymphoma-2 (Bcl-2) in MG-63 cells. The anticancer effects of HCPT were demonstrated to significantly activate the protein expression of p53, PARP-1 and cytochrome c, and suppress Bcl-2 protein expression and promote the activity of caspase-9 and caspase-3 in human osteosarcoma cells. In conclusion, the anticancer effects of HCPT appear to induce the apoptosis of human osteosarcoma cells through the activation of the caspase-3, p53 and cytochrome c pathways.
... Therefore, such a result could reveal that HepG2 cells were much more sensitive to LPC CM than to the free LUT. A final concentration which was less than IC 50% (24 μg/ml) was appropriate to be used in the following cell uptake experiments [43]. ...
... Regarding quantitative determination of cellular uptake, it was reported that the charge of the nanocarriers may affect the process of cellular uptake [47]. In the present study, LPC CM and LUT CM possessed a negative ζ potential (-41.8 ± 5.40 and -46.1 ± 6.14 mV, respectively), these anionic nanocarriers might interact with the cationic sites of the proteins in cell membrane leading to endocytosis [43,47]. Subsequently, CMs were supposed to improve the cellular absorption and the uptake efficacy of LUT in HepG2 cells compared with free LUT. ...
Aim:
A novel luteolin (LUT) loaded dual bionanocarrier 'phytochylomicron' was elaborated to allow LUT injectable delivery and liver cancer targeting.
Methods:
LUT-phospholipid complex was prepared and loaded into chylomicron nanocarrier. Then phytochylomicron underwent physicochemical characterization, cell culture and pharmacodynamics studies on a new liver-tumor model.
Results:
Phytochylomicron showed sustained release pattern with minimum drug leakage until reaching the liver. Cell culture studies showed high growth inhibition of Hep G2 cells with 2.6-fold enhancement in cellular uptake. Pharmacodynamics demonstrated enhanced tumor growth inhibition (sixfold) with a significant tumor size reduction. Finally, cell culture results demonstrated an excellent correlation with pharmacodynamics confirming the obtained findings.
Conclusion:
A novel phytochylomicron nanosystem was successfully elaborated with promising characteristics that promoted injectable LUT delivery and liver cancer targeting. [Formula: see text].
... In recent years, SMNs are emerging as potential DDSs because of their defined structure and tailored properties. Hence, the use of small molecule nanoparticles as drug carriers has been widely explored, which can deliver drugs via different mechanisms, such as encapsulation [52] and conjugation [53e57]. ...
Nanoscale drug delivery systems (DDSs) have emerged as promising candidates for cancer therapy. However, traditional nanoscale DDSs suffer from several inherent drawbacks, including sophisticated synthesis, uncontrolled structure, low drug loading capacity, high reticuloendothelial system (RES) accumulation, unpredicted metabolic mechanism, and so on. In order to solve these problems, nanodrugs self-assembled from small molecules containing anticancer drugs have received great attention in recent years. Different from traditional nanoscale DDSs, small molecule nanodrugs (SMNs) exhibit unique advantages, such as simple synthesis, defined structure, high drug loading capacity, excellent tumor accumulation and low-toxic metabolism pathway. Hence, with rational design, SMNs can achieve excellent cancer therapeutic efficacy as well as low side effects, extremely promising for the clinic translation. Up to now, significant progress has been made for the exploration of SMNs for cancer therapy. In this review, we briefly summarize the design and synthesis, biological properties, as well as their wide range of applications for cancer therapy.
... Various approaches have been evaluated to overcome the challenges associated with ERL therapy exemplified by cyclodextrin complex (Devasari et al., 2015), reverse micelle loaded lipid nanoparticles (Vrignaud et al., 2012), poly (d,llactic-co-glycolic acid) nanoparticles (Marslin et al., 2009), hybrid nanoparticles (Jesson et al., 2014), liposomes (Morton et al., 2014;Trummer, 2010), and other types of nanoparticles (Liversidge & Jenkins, 2012a,b). In this regard, there exists immense potential of complexing therapeutic active constituents with nanosponges for improving oral bioavailability and therapeutic efficacy (Hüsch et al., 2011;Maiti, Mukherjee, Gantait, Saha, & Mukherjee, 2007;Wei et al., 2010;Yanyu, Yunmei, Zhipeng, & Qineng, 2006). ...
... However, a major concern of MMC was in the narrow therapeutic index and serious side effects such as severe myelosuppression and gastrointestinal complications [19,20]. Recently, the drug-phospholipid complex had received significant attention [21,22] because of the significant improvement of drug efficacy and safety [23][24][25][26][27][28][29][30]. To address the issue, we prepared the MMCsoybean phosphatidyhlcholine complex (MMC-SPC complex) to increase the effectiveness of MMC [31]. ...
Mitomycin C is one of the most effective chemotherapeutic agents for a wide spectrum of cancers, but its clinical use is still hindered by the mitomycin C (MMC) delivery systems. In this study, the MMC-loaded polymer-lipid hybrid nanoparticles (NPs) were prepared by a single-step assembly (ACS Nano 2012, 6:4955 to 4965) of MMC-soybean phosphatidyhlcholine (SPC) complex (Mol. Pharmaceutics 2013, 10:90 to 101) and biodegradable polylactic acid (PLA) polymers for intravenous MMC delivery. The advantage of the MMC-SPC complex on the polymer-lipid hybrid NPs was that MMC-SPC was used as a structural element to offer the integrity of the hybrid NPs, served as a drug preparation to increase the effectiveness and safety and control the release of MMC, and acted as an emulsifier to facilitate and stabilize the formation. Compared to the PLA NPs/MMC, the PLA NPs/MMC-SPC showed a significant accumulation of MMC in the nuclei as the action site of MMC. The PLA NPs/MMC-SPC also exhibited a significantly higher anticancer effect compared to the PLA NPs/MMC or free MMC injection in vitro and in vivo. These results suggested that the MMC-loaded polymer-lipid hybrid NPs might be useful and efficient drug delivery systems for widening the therapeutic window of MMC and bringing the clinical use of MMC one step closer to reality.
