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IC50 of A549 cells after 24-, 48-, 72-h incubation with paclitaxel formulated in the Taxol W , CNP, UNP, and TNP
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Oral chemotherapy is a key step towards 'chemotherapy at home', a dream of cancer patients, which will radically change the clinical practice of chemotherapy and greatly improve the quality of life of the patients. In this research, three types of nanoparticle formulation from commercial PCL and self-synthesized d-alpha-tocopheryl polyethylene glyc...
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... advantages in cytotoxicity of the TNP > UNP > Taxol W can be quantitatively analyzed by IC 50 , which can be determined by constructing a dose-response curve. Table 2 shows IC 50 values of A549 cells after 24-, 48-, 72-h incubations with paclitaxel formulated in CNP, UNP, TNP, and Taxol W , respectively, which are obtained from Figure 6. The data showed that the IC 50 values for A549 cells were reduced from 2.609, 1.645, and 0.910 to 0.201, 0.122, and 0.106 μg/ml for TNP after 24, 48 and 72 h, re- spectively. ...
Citations
... PEGylated liposomes, altered with fibronectin-mimetic peptides, have shown promise in targeting metastatic colon tumor cells overexpressing specific receptors (Yani et al., 2020). Nanoparticle systems like TPGS 1000 and pluronic block copolymers have been proven to increase the cytotoxicity of cancer cells and inhibit drug efflux (Jiang et al., 2013;Cavalcante de Freitas et al., 2023). Folate acid ligands on NPs have facilitated specific accumulations in drug-resistant cancer cells (Shmendel et al., 2023). ...
In the realm of healthcare, the fundamental right to access high-quality, timely, and affordable services has long been a focal point for the development of innovative technologies. Technological progress has played a pivotal role in improving healthcare outcomes. Notably, the field of nanoscience has given rise to a new generation of nanostructures, each endowed with remarkable properties that underpin their astonishing applications. Since its inception, nanotechnology has exerted a profound influence on healthcare, ushering in a new era of transformative advancements. Over the past two decades, nanotechnology has steadily expanded its presence, catalyzed by extensive research across diverse healthcare sectors. The integration of nanotechnology into medicine has given rise to the field of nanomedicine, which has yielded a plethora of benefits in disease prevention, diagnosis, and treatment. Within the realm of nanomedicine, various nanosystems have emerged as superior candidates for theranostic purposes when compared to conventional approaches. This chapter aims to illuminate the significance of medically relevant nanosystems, exploring their applications and acknowledging their limitations in pivotal areas such as gene therapy, targeted drug delivery, and the treatment of cancer and genetic diseases. While nanotechnology holds immense potential to revolutionize healthcare, it remains an underutilized resource. This chapter underscores the need for concerted efforts to overcome its current limitations and fully harness its potential, envisioning a future where nanotechnology plays a central role in reshaping the healthcare landscape.
... To solve this problem, Liqin Jiang et al developed thiolated chitosan-modified PLA-PCL-TPGS (poly (lactide-co ε-caprolactone)-d-αtocopheryl polyethylene glycol 1000 succinate) nanoparticles to increase paclitaxel transport by opening tight junctions and bypassing the efflux pump of p-glycoprotein. 100,101 Jian Hou et al induced a paclitaxel-loaded mixed micelle (PTX-TP-M) with vitamin E-TPGS (TPGS) and Plasdone ® S-630 Copovidone (PVPS 630), with vitamin E-TPGS enhancing permeability for intestinal absorption and acting as a p-glycoprotein inhibitor. 102 The mixed micelles contain paclitaxel inside, with TPGS having a high affinity for the membranes of lung cancer cells. ...
Lung cancer is one of the most common malignant tumors worldwide and is characterized by high morbidity and mortality rates and a poor prognosis. It is the leading cause of cancer-related death in the United States and worldwide. Most patients with lung cancer are treated with chemotherapy, radiotherapy, or surgery; however, effective treatment options remain limited. In this review, we aim to provide an overview of clinical trials, ranging from Phase I to III, conducted on drug delivery systems for lung cancer treatment. The trials included oral, inhaled, and intravenous administration of therapeutics. Furthermore, the study also talks about the evolving paradigm of targeted therapy and immunotherapy providing promising directions for personalized treatment. In addition, we summarize the best results and limitations of these drug delivery systems and discuss the potential capacity of nanomedicine.
... A modified version of the everted sac model was used to examine the passage of RIS through the intestinal barrier [27,28]. Following overnight fasting, animals were administered diethyl ether anaesthesia before being sacrificed via cervical dislocation. ...
Risedronate sodium (RIS) exhibits limited bioavailability and undesirable gastrointestinal effects when administered orally, necessitating the development of an alternative formulation. In this study, mPEG-coated nanoparticles loaded with RIS-HA-TCS were created for osteoporosis treatment. Thiolated chitosan (TCS) was synthesized using chitosan and characterized using DSC and FTIR, with thiol immobilization assessed using Ellman’s reagent. RIS-HA nanoparticles were fabricated and conjugated with synthesized TCS. Fifteen batches of RIS-HA-TCS nanoparticles were designed using the Box–Behnken design process. The nanoparticles were formulated through the ionic gelation procedure, employing tripolyphosphate (TPP) as a crosslinking agent. In silico activity comparison of RIS and RIS-HA-TCS for farnesyl pyrophosphate synthetase enzyme demonstrated a higher binding affinity for RIS. The RIS-HA-TCS nanoparticles exhibited 85.4 ± 2.21% drug entrapment efficiency, a particle size of 252.1 ± 2.44 nm, and a polydispersity index of 0.2 ± 0.01. Further conjugation with mPEG resulted in a particle size of 264.9 ± 1.91 nm, a PDI of 0.120 ± 0.01, and an encapsulation efficiency of 91.1 ± 1.17%. TEM confirmed the spherical particle size of RIS-HA-TCS and RIS-HA-TCS-mPEG. In vitro release studies demonstrated significantly higher release for RIS-HS-TCS-mPEG (95.13 ± 4.64%) compared to RIS-HA-TCS (91.74 ± 5.13%), RIS suspension (56.12 ± 5.19%), and a marketed formulation (74.69 ± 3.98%). Ex vivo gut permeation studies revealed an apparent permeability of 0.5858 × 10−1 cm/min for RIS-HA-TCS-mPEG, surpassing RIS-HA-TCS (0.4011 × 10−4 cm/min), RIS suspension (0.2005 × 10−4 cm/min), and a marketed preparation (0.3401 × 10−4 cm/min).
... 9 Moreover, numerous thiolated nanomedicines have been developed that have improved anticancer effects, such as mesoporous silica nanoparticles (NPs), 10 β-cyclodextrin modified iron oxide NPs, 11 chitosan NPs, 12 gold NPs, 13 and chitosan-modified TPGS copolymer NPs. 14 However, our previous research has demonstrated that folateand EGFR (dual)-targeted NPs of CZT are particularly successful in targeting specifically to cancer sites. 15 Furthermore, the efficiency of dual-receptor targeted NPs can be enhanced by adopting redox-sensitive properties. ...
... A modified version of the everted sac model was used to examine the passage of RIS through the intestinal barrier [25,26]. Following an overnight fasting, animals were administered diethyl ether anaesthesia before being sacrificed via cervical dislocation. ...
Risedronate sodium (RIS) possesses very low bioavailability and several adverse effects in the gastrointestinal tract when administered through an oral route. Thus, this necessitates the need to develop novel formulation. Hence, we had developed RIS-HA-TCS loaded mPEG coated nanoparticles for the treatment of osteoporosis. Chitosan was used to synthesize thiolated chitosan and its characterization was done using DSC and FTIR. Ellman's reagent was used to measure the degree of thiol immobilization. The RIS-HA fabrication was done and was further conjugated with the synthesized TCS. The Box-Behnken design process was used for designing fifteen batches of RIS-HA-TCS nanoparticles, which were formulated by ionic gelation procedure in which tripolyphosphate (TPP) was used as a crosslinking agent. Moreover, RIS and RIS-HA-TCS in-silico activity was compared for farnesyl pyrophosphate synthetase enzyme. The obtained results revealed that the binding affinity of RIS was much more than the conjugated RIS. Successful docking results paved the way for thiolation of chitosan with RIS. The drug entrapment efficiency (%EE), particle size and Polydispersity index (PDI) of RIS-HA-TCS nanoparticles obtained were 85.4 ±2.21%, 252.1 ±2.44 nm and 0.2± 0.01 respectively. The particle size, PDI, and encapsulation efficiency of RIS-HA-TCS were reported to be 264.9 ±1.91 nm, 0.120± 0.01, and 91.1 ±1.17%, respectively, after being further conjugated with mPEG. TEM showed the spherical particle size of RIS-HA-TCS and RIS-HA-TCS-mPEG. The in-vitro release of RIS-HS-TCS-mPEG was found to be significantly higher (95.13±4.64%) as compared to RIS-HA-TCS (91.74 ± 5.13%), RIS suspension (56.12 ± 5.19%) and marketed formulation (74.69 ± 3.98%). In an ex-vivo gut permeation study, RIS-HA-TCS-mPEG nanoparticles was found to have an apparent permeability of 0.5858×10-1 cm/min which was better than the apparent permeabilities of RIS-HA-TCS formulation (0.4011 ×10-4cm/min), RIS suspension (0.2005 ×10-4 cm/min) and marketed preparation (0.3401 ×10-4 cm/min)..
... Polymeric nanoparticle research is gaining attraction due to the possibility of applications in cancer therapy [7]. Because of their small size and larger specific area, nanoparticles absorb more drugs than larger drug carriers [8]. Chitosan is one of the most prevalent polysaccharides and polymers that have been discovered to have a variety of biological functions, including bio adhesion, physicochemical properties, and permeability-enhancing capabilities, making it a unique material for the development of drug delivery systems [9]. ...
... | NOT PEER-REVIEWED | Posted: 2 August 2023 doi:10.20944/preprints202308.0141.v1 8 Where, F0, F denotes fluorescence intensities in the absence and presence of quencher, respectively. ...
The current study describes the preparation of chitosan nanoparticles (CNPs) using hydroxychloroquine (HCQ), widely used in traditional medicine due to its diverse phar-macological and medicinal uses. This work aims to combine the HCQ drug with CS NPs to generate a novel nanocomposite with improved characteristics and bioavailability. HCQ@CS NPs is roughly shaped like roadways and has a smooth surface with an average size of 159.3±7.1 nm, a PdI of 0.224±0.101, and a zeta potential of +46.6±0.8 mV. To aid in the development of pharmaceutical systems for use in cancer therapy, the binding mech-anism and affinity of the interaction between HCQ and HCQ@CS NPs and BSA were ex-amined using stopped-flow, other spectroscopic approaches, supplemented by molecular docking analysis. HCQ and HCQ@CS NPs binding with BSA is driven by a ground-state complex formation that may be accompanied by a non-radiative energy transfer process, and binding constants indicated that HCQ@CS NPs-BSA was more stable than HCQ-BSA. The stopped-flow analysis demonstrated that, in addition to increasing BSA affinity, the nano formulation HCQ@CS NPS changes the binding process and may open up new routes for interaction. Docking experiments verified the development of the HCQ-BSA complex, with HCQ binding to the site I on the BSA structure, primarily with the amino acids Thr 578, Gln 579, Gln 525, Tyr 400, and Asn 404. Furthermore, the nano-formulation HCQ@CS NPS not only increased cytotoxicity against the A549 lung cancer cell line (IC50 = 28.57±1.72 g/ml) compared to HCQ (102.21±0.67) g/ml), but also exhibited higher anti-bacterial activity against both Gram-positive and Gram-negative bacteria when compared to HCQ and chloramphenicol which in agreement with the binding constants. The nano formulation developed in this study may offer a viable therapy option for A549 lung cancer.
... These small nanoparticles may transport into the microcirculation through the paracellular route, but the amount transported is marginal relative to the overall absorption. Otherwise, some exquisitely designed nanoparticles can traverse the intestinal epithelium into the underlying microcirculation through this pathway by temporarily opening the TJs [51][52][53] . Although the paracellular route is not the predominant J o u r n a l P r e -p r o o f transport pattern of nanoparticles, it can circumvent lysosomal digestion due to not entering the cell, which is conducive to the realization of OTDDS. ...
Targeted drug delivery is constantly updated with a better understanding of the physiological and pathological features of various diseases. Depending on high safety, good compliance and many other undeniable advantages, attempts have been undertaken to complete an intravenous-to-oral conversion of targeted drug delivery. However, oral delivery of particulates to systemic circulation is highly challenging due to the biochemical aggressivity and immune exclusion in the gut that restrain absorption and access to the bloodstream. Little is known about the feasibility of targeted drug delivery via oral administration (oral targeting) to a remote site beyond the gastrointestinal tract. To this end, this review proactively contributes to a special dissection on the feasibility of oral targeting. We discussed the theoretical basis of oral targeting, the biological barriers of absorption, the in vivo fate and transport mechanisms of drug vehicles, and the effect of structural evolution of vehicles on oral targeting as well. At last, a feasibility analysis on oral targeting was performed based on the integration of currently available information. The innate defense of intestinal epithelium does not allow influx of more particulates into the peripheral blood through enterocytes. Therefore, limited evidence and lacking exact quantification of systemically exposed particles fail to support much success with oral targeting. Nevertheless, the lymphatic pathway may serve as a potentially alternative portal of peroral particles into the remote target sites via M-cell uptake.
... C6-ES-NP + are mostly internalized by endocytosis and passive targeting [40]. Also, the positive charge on their surface could benefit the interaction with the negatively charged cell membrane [42]. HA coating of the nanoparticles significantly improved cellular uptake which is mostly due to HA interaction with its major cell surface receptor CD44, consequently, resulting in nanoparticle internalization via receptor-mediated endocytosis. ...
Inflammatory bowel disease (IBD) is characterized by chronic inflammation along the gastrointestinal tract. For IBD effective treatment, developing an orally administered stable drug delivery system capable of targeting inflammation sites is a key challenge. Herein, we report pH responsive hyaluronic (HA) coated Eudragit S100 (ES) nanoparticles (NPs) for the targeted delivery of budesonide (BUD) (HA-BUD-ES-NPs). HA-BUD-ES-NPs showed good colloidal properties (274.8 ± 2.9 nm and − 24.6 ± 2.8 mV) with high entrapment efficiency (98.3 ± 3.41%) and pH-dependent release profile. The negative potential following incubation in simulated gastrointestinal fluids reflected the stability of HA coat. In vitro studies on Caco-2 cells showed HA-BUD-ES-NPs biocompatibility and enhanced cellular uptake and anti-inflammatory effects as shown by the significant reduction in IL-8 and TNF-α. The oral administration of HA-BUD-ES-NPs in an acetic acid induced colitis rat model significantly mitigated the symptoms of IBD, and improved BUD therapeutic efficacy compared to drug suspension. This was proved via the improvement in disease activity index and ulcer score in addition to refined histopathological findings. Also, the assessment of inflammatory markers, epithelial cadherin, and mi-R21 all reflected the higher efficiency of HA-BUD-ES-NPs compared to free drug and uncoated formulation. We thus suggest that HA-BUD-ES-NPs provide a promising drug delivery platform for the management and site specific treatment of IBD.
Graphical Abstract
... Taxol® was less effective at killing A549 cells in vitro than thiolated CS-modified PLA-Paclitaxel-TPGS NPs. P-glycoprotein efflux pump may be bypassed by the mucoadhesive NPs, increasing paclitaxel delivery [38]. By loading Morinda citrifolia essential oil with CS, researchers increased its anti-cancer efficacy against A549 cells. ...
... The biodegradable polymer is used frequently as a carrier for bioactive compounds to improve its bioavailability, encapsulation efficiency, controlled release kinetics, and targeted delivery to the organ without producing any toxicity into the body metabolism (34,29,35,36). Physicochemical properties like zeta potential or stability, particle size, and size distribution are some distinct characteristics that determine toxicity effects, better biological functionality, and targeting ability of NPs in-vivo (37,38,39,40,19,41,42,13). Many studies have investigated that nano-sized particles have several benefits over micro-particles-based drug delivery systems (43,44,45) due to their higher intracellular uptake compared to microparticles (22,46,47,36). ...
... When polymers are used to encapsulate bioactive compounds in the presence of surfactants are known as polymeric NPs (146,136,42) (Figure 4E). The primary significance of these particles is to protect the encapsulated bioactive ingredients from external environmental factors and enzymatic digestion (147). ...
Lycopene, rich in red, yellow, or orange-colored fruits and vegetables, is the most potent antioxidant among the other carotenoids available in human blood plasma. It is evident that regular lycopene intake can prevent chronic diseases like cardiovascular diseases, type-2 diabetes, hypertension, kidney diseases and cancer. However, thermal processing, light, oxygen, and enzymes in gastrointestinal tract (GIT) compromise the bioaccessibility and bioavailability of lycopene ingested through diet. Nanoencapsulation provides a potential platform to prevent lycopene from light, air oxygen, thermal processing and enzymatic activity of the human digestive system. Physicochemical properties evidenced to be the potential indicator for determining the bioaccessibility of encapsulated bioactive compounds like lycopene. By manipulating the size or hydrodynamic diameter, zeta potential value or stability, polydispersity index or homogeneity and functional activity or retention of antioxidant properties observed to be the most prominent physicochemical properties to evaluate beneficial effect of implementation of nanotechnology on bioaccessibility study. Moreover, the molecular mechanism of the bioavailability of nanoparticles is not yet to be understood due to lack of comprehensive design to identify nanoparticles' behaviors if ingested through oral route as functional food ingredients. This review paper aims to study and leverage existing techniques about how nanotechnology can be used and verified to identify the bioaccessibility of lycopene before using it as a functional food ingredient for therapeutic treatments.
