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Cancer is among the most dreadful fatal diseases globally, and the efficacy of recent chemotherapeutic approaches is limited due to many related drawbacks. The major limitation associated with cancer chemotherapy is the poor aqueous solubility of most of the anticancer drugs, development of multidrug resistance, low bioavailability, small plasma half-life, and serious side effects to healthy tissues due to unspecific distribution of chemotherapeutic drugs. Advancement in nanoscience provides the means of specific and selective targeting of cancer cells. Chitosan, one of the naturally occurring biocompatible and mucoadhesive biopolymers that have been widely used in recent years for the effective delivery of anti-cancer drugs at the target site. Chitosan nanoparticles can encapsulate both hydrophilic and lipophilic chemotherapeutic drugs, proteins/peptides as well as different genetic materials like DNA, miRNA, siRNA, etc. in their polymeric matrix. Due to the unique polymeric matrix, these nanoparticles improve the solubility as well as the stability of encapsulated molecules in the biological system. Chitosan nanoparticles can improve the pharmacokinetic profile as well as the therapeutic efficacy of encapsulated drugs by controlling the release rates and targeted delivery process. These nanoparticles selectively deliver the encapsulated drugs to desired sites through passive or active targeting mechanisms thereby decrease the undesirable side-effects. The surface of chitosan nanoparticles can be modified with different ligands like antibodies, proteins, peptides, polysaccharides, and nucleic acids to achieve selective targeting. This review will provide a state-of-the-art perspective on recent development in chitosan-nanoparticles for smart anti-cancer therapeutic delivery. [ABSTRACT FROM AUTHOR]

Polymer-lipid hybrid nanoparticles (PLHNPs) are novel nanoplatforms for the effective delivery of a lipophilic drug in the management of a variety of solid tumors. The present work was designed to develop exemestane (EXE) encapsulated D-alpha-tocopheryl polyethylene glycol succinate (TPGS) based PLHNPs (EXE-TPGS-PLHNPs) for controlled delivery of EXE for breast cancer management. EXE-TPGS-PLHNPs were formulated by single-step nano-precipitation technique and statistically optimized by a 33 Box–Behnken design using Design expert® software. The polycaprolactone (PCL; X1), phospholipon 90 G (PL-90G; X2), and surfactant (X3) were selected as independent factors while particles size (PS; Y1), polydispersity index (PDI; Y2), and %entrapment efficiency (%EE; Y3) were chosen as dependent factors. The average PS, PDI, and %EE of the optimized EXE-TPGS-PLHNPs was observed to be 136.37 ± 3.27 nm, 0.110 ± 0.013, and 88.56 ± 2.15% respectively. The physical state of entrapped EXE was further validated by Fourier-transform infrared spectroscopy, differential scanning calorimetry, and powder x-ray diffraction that revealed complete encapsulation of EXE in the hybrid matrix of PLHNPs with no sign of significant interaction between drug and excipients. In vitro release study in simulated gastrointestinal fluids revealed initial fast release for 2 h after that controlled release profile up to 24 h of study. Moreover, optimized EXE-TPGS-PLHNPs exhibited excellent stability in gastrointestinal fluids as well as colloidal stability in different storage concentrations. Furthermore, EXE-TPGS-PLHNPs exhibited distinctively higher cellular uptake and time and dose-dependent cytotoxicity against MCF-7 breast tumor cells compared to EXE-PLHNPs without TPGS and free EXE. The obtained results suggested that EXE-TPGS-PLHNPs can be a promising platform for the controlled delivery of EXE for the effective treatment of breast cancer. [ABSTRACT FROM AUTHOR]

The present research work was designed to develop dorzolamide-loaded chitosan-coated polycaprolactone nanoparticles (DRZ-CS-PCL-NPs) for improved ocular delivery. The nanoparticles were prepared by single-step emulsification technique and optimized using the three-factor three-level Box-Behnken design. The optimized DRZ-CS-PCL-NPs prepared with the composition of polycaprolactone (60 mg), chitosan (0.6%) and polyvinyl alcohol (1.5%). The particle size, polydispersity index, zeta potential and encapsulation efficiency of optimized DRZ-CS-PCL-NPs were found to be 192.38 ± 6.42 nm, 0.18 ± 0.04, +5.21 ± 1.24 mV, and 72.48 ± 5.62%, respectively. The dependent and independent response variables showed excellent correlation and signifying the rationality of the optimized DRZ-CS-PCL-NPs. The DRZ release from CS-PCL-NPs showed biphasic behaviour with initial burst release for 2 h after that sustained-release up to 12 h of study. The corneal flux experiment showed many fold enhancement in permeation across goat cornea. DRZ-CS-PCL-NPs exhibited 3.7 fold higher mucoadhesive strength compared to the control. Furthermore, the histopathological assessment and HET-CAM study revealed that the DRZ-CS-PCL-NPs were non-irritant and safe for ocular administration. Therefore, from the present study, it can be concluded that the optimized DRZ-CS-PCL-NPs are safe and have the potential for successful ocular delivery and improved therapeutic efficacy. [ABSTRACT FROM AUTHOR]

In the present study, sulforaphane (SFN)-loaded nanostructured lipid carriers (NLC) were developed and optimized for improved oral efficacy against cancer. The SFN-loaded NLC formulation was developed by melt emulsification ultrasonication technique and optimized by Box-Behnken statistical design. The optimized SFN-loaded NLC formulation composed of precirol® ATO 5 (solid lipid) and vitamin E (liquid lipid) as lipid phase (3% w/v), poloxamer 188 (1%) and Tween 80 (1%) as surfactant. The mean particle size, polydispersity index, zeta potential, entrapment efficiency (%) and drug loading (%) of optimized SFN-loaded NLC formulation was observed to be 145.38 ± 4.46 nm, 0.181 ± 0.023, −25.12 ± 2.36 mV, 84.94 ± 3.82% and 14.82 ± 3.46%, respectively. In vitro drug release studies showed that the release of SFN from optimized NLC formulation was significantly higher (86.52 ± 5.48%) compared to SFN suspension (38.47 ± 5.52%) up to 24 h. Ex vivo gut permeation studies revealed a very good enhancement in permeation of drug present in the NLC compared to plain SFN solution and were further confirmed by CLSM. MTT assay in different cancer cell lines showed that the optimized SFN-loaded NLC formulation exhibited significantly improved (p < .05) cytotoxicity compared to free SFN solution. SFN-loaded NLC formulation showed significantly improved antioxidant activity compared to free SFN solution. Furthermore, pharmacokinetic study on albino Wistar rats showed 5.04-fold increase in relative oral bioavailability with NLC (p < .05) compared to SFN suspension. Therefore, NLC represents a great potential for improved efficacy of SFN after oral administration. [ABSTRACT FROM AUTHOR]

Cancer continues to be one in all the leading reasons for death worldwide. The mean cancer survival through standard therapeutic strategies has not been significantly improved over the past few decades. Hence, alternate remedies are needed to treat this terrible disease. Recently, natural compounds present in the plants, i.e. phytochemicals have been widely exploited for their anticancer potential. Phytochemicals may exhibit their anticancer activity through targeting different cancer cell signalling pathways, promoting cell cycle arrest and apoptosis, regulating antioxidant status and detoxification. Despite their excellent anticancer activity, the phytochemicals are limited by their low aqueous solubility, poor bioavailability, and poor penetration into cells, hepatic disposition, narrow therapeutic index and rapid uptake by normal tissues. Therefore, to address these challenges, the scientific community has shifted its significant interests towards nanocarriers-based delivery of phytochemicals due to their ability to enhance aqueous solubility, and bioavailability, specific tumour cell/tissue targeting, improved cellular uptake, reducing doses of phytochemicals and achieving steady-state therapeutic levels of the phytochemicals over an extended period of time. Additional advantages include excellent blood stability, multifunctional design of nanocarriers and improvement in anticancer activities. This review aims to summarise recent progress in phytochemical based nanomedicines for effective treatment of cancer. [ABSTRACT FROM AUTHOR]

Cancer has been growing nowadays consequently high number of death ascertained worldwide. The medical intervention involves chemotherapy, radiation therapy and surgical removal. This conventional technique lacking targeting potential and harm the normal cells. In drug treatment regimen, the combination therapy is preferred than single drug treatment module due to higher internalization of chemotherapeutics in the cancer cells both by enhance permeation retention effect and by direct cell apoptosis. The cancer therapeutics involves different methodologies of delivering active moiety to the target site. The active and passive transport mode of chemotherapeutic targeting utilizes advance nanocarriers. The nanotechnological strategic treatment applying advance nanocarrier greatly helps in mitigating the cancer prevalence. The nanocarrier-incorporating nanodrug directed for specific area appealed scientist across the globe and issues to be addressed in this regard. Therefore, various techniques and approaches invented to meet the objectives. With the advances in nanomedicine and drug delivery, this review briefly focused on various modes of nanodrug delivery including nanoparticles, liposomes, dendrimer, quantum dots, carbon nanotubes, metallic nanoparticles, nanolipid carrier (NLC), gold nanoshell, nanosize cantilevers and nanowire that looks promising and generates a novel horizon in cancer therapeutics. [ABSTRACT FROM AUTHOR]

[Display omitted] Exemestane (EXE), an irreversible aromatase inhibitor, is primarily used as a first-line therapy for estrogen receptor-positive breast cancer patients. However, complex physicochemical characteristics of EXE limit its oral bioavailability (<10%) and anti-breast cancer efficacy. The present study aimed to develop a novel nanocarrier system to improve the oral bioavailability and anti-breast cancer efficacy of EXE. In this perspective, EXE-loaded TPGS-based polymer lipid hybrid nanoparticles (EXE-TPGS-PLHNPs) were prepared by the nanoprecipitation method and evaluated for their potential in improving oral bioavailability, safety, and therapeutic efficacy in the animal model. EXE-TPGS-PLHNPs showed significantly higher intestinal permeation in comparison to EXE-PLHNPs (without TPGS) and free EXE. After oral administration, EXE-TPGS-PLHNPs and EXE-PLHNPs revealed 3.58 and 4.69 times higher oral bioavailability in Wistar rats compared to the conventional EXE suspension. The results of the acute toxicity experiment suggested that the developed nanocarrier was safe for oral administration. Furthermore, EXE-TPGS-PLHNPs and EXE-PLHNPs represented much better anti-breast cancer activity in Balb/c mice bearing MCF-7 tumor xenograft with tumor inhibition rate of 72.72% and 61.94% respectively in comparison with the conventional EXE suspension (30.79%) after 21 days of oral chemotherapy. In addition, insignificant changes in the histopathological examination of vital organs and hematological analysis further confirm the safety of the developed PLHNPs. Therefore, the findings of the present investigation advocated that the encapsulation of EXE in PLHNPs can be a promising approach for oral chemotherapy of breast cancer. [ABSTRACT FROM AUTHOR]

In the present study, sulforaphane (SFN)-loaded nanostructured lipid carriers (NLC) were developed and optimized for improved oral efficacy against cancer. The SFN-loaded NLC formulation was developed by melt emulsification ultrasonication technique and optimized by Box–Behnken statistical design. The optimized SFN-loaded NLC formulation composed of precirol® ATO 5 (solid lipid) and vitamin E (liquid lipid) as lipid phase (3% w/v), poloxamer 188 (1%) and Tween 80 (1%) as surfactant. The mean particle size, polydispersity index, zeta potential, entrapment efficiency (%) and drug loading (%) of optimized SFN-loaded NLC formulation was observed to be 145.38 ± 4.46 nm, 0.181 ± 0.023, −25.12 ± 2.36 mV, 84.94 ± 3.82% and 14.82 ± 3.46%, respectively. In vitro drug release studies showed that the release of SFN from optimized NLC formulation was significantly higher (86.52 ± 5.48%) compared to SFN suspension (38.47 ± 5.52%) up to 24 h. Ex vivo gut permeation studies revealed a very good enhancement in permeation of drug present in the NLC compared to plain SFN solution and were further confirmed by CLSM. MTT assay in different cancer cell lines showed that the optimized SFN-loaded NLC formulation exhibited significantly improved (p <.05) cytotoxicity compared to free SFN solution. SFN-loaded NLC formulation showed significantly improved antioxidant activity compared to free SFN solution. Furthermore, pharmacokinetic study on albino Wistar rats showed 5.04-fold increase in relative oral bioavailability with NLC (p <.05) compared to SFN suspension. Therefore, NLC represents a great potential for improved efficacy of SFN after oral administration. [ABSTRACT FROM AUTHOR]

In the present study, rosuvastatin calcium-loaded nanostructured lipid carriers were developed and optimized for improved efficacy. The ROS-Ca-loaded NLC was prepared using melt emulsification ultrasonication technique and optimized by Box–Behnken statistical design. The optimized NLC composed of glyceryl monostearate (solid lipid) and capmul MCM EP (liquid lipid) as lipid phase (3% w/v), poloxamer 188 (1%) and tween 80 (1%) as surfactant. The mean particle size, polydispersity index (PDI), zeta potential (ζ) and entrapment efficiency (%) of optimized NLC formulation was observed to be 150.3 ± 4.67 nm, 0.175 ± 0.022, −32.9 ± 1.36 mV and 84.95 ± 5.63%, respectively. NLC formulation showed betterin vitrorelease in simulated intestinal fluid (pH 6.8) than API suspension. Confocal laser scanning showed deeper permeation of formulation across rat intestine compared to rhodamine B dye solution. Pharmacokinetic study on female albino Wistar rats showed 5.4-fold increase in relative bioavailability with NLC compared to API suspension. Optimized NLC formulation also showed significant (p < 0.01) lipid lowering effect in hyperlipidemic rats. Therefore, NLC represents a great potential for improved efficacy of ROS-Ca after oral administration. [ABSTRACT FROM PUBLISHER]

Cancer development is associated with abnormal, uncontrolled cell growth and causes significant economic and social burdens to society. The global statistics of different cancers have been increasing because of the aging population, and the increasing prevalence of risk factors such as stress condition, overweight, changing reproductive patterns, and smoking. The prognosis of cancer treatment is high, if diagnosed in the early stage. Late-stage diagnosis, however, is still a big challenge for the clinician. The usual treatment scheme involves chemotherapy and surgery followed by radiotherapy. Chemotherapy is the most widely used therapeutic approach against cancer. However, it suffers from the major limitation of poor delivery of anticancer therapeutics to specific cancer-targeted tissues/cells. Nanomedicines, particularly nanostructured lipid carriers (NLCs) can improve the efficacy of encapsulated payload either through an active or passive targeting approach against different cancers. The targeted nanomedicine can be helpful in transporting drug carriers to the specifically tumor-targeted tissue/cells while sparing abstaining from the healthy tissue/cells. The active targeting utilizes the binding of a specific cancer ligand to the surface of the NLCs, which improves the therapeutic efficacy and safety of the cancer therapeutics. This review shed light on the utilization of NLCs system for targeted therapy in different cancers. Furthermore, modification of NLCs as cancer theranostics is a recent advancement that is also discussed in the manuscript with a review of contemporary research carried out in this field. [Display omitted] • NLCs as second generation lipid nanocarrier gained attention for cancer treatment. • It can be exploited to deliver wide variety of cancer therapeutics. • The efficacy of encapsulated therapeutic improved significantly in cancer by NLCs. • Recent advancement leads its applicability as cancer theranostics. • Biocompatible lipids nature of NLCs makes them candidates of clinical significance. [ABSTRACT FROM AUTHOR]

The major limitation with the oral administration of most of the phytochemicals is their low aqueous solubility and bioavailability. Thymoquinone (THQ) is one of the most widely used phytochemicals used to treat a variety of diseases. However, strong lipophilic characteristics limit its clinical application. Therefore, this study was aimed to design novel chitosan (C) modified polycaprolactone (PL) nanoparticles (NPs) for improved oral bioavailability of THQ. THQ-CPLNPs was optimized 33-Box-Behnken design. After that, the optimized THQ-CPLNPs was characterized by different parameters. THQ-CPLNPs showed the size, PDI, and ZP of 182.32 ± 6.46nm, 0.179 ± 0.012, and þ21.36 ± 1.22 mV, respectively. The entrapment and loading capacity were found to be 79.86 ± 4.36%, and 13.45 ± 1.38%, respectively. THQ-CPLNPs exhibited burst release in initial 2 h followed by prolonged release up to 24 h in simulated intestinal fluids. THQ-CPLNPs showed excellent mucoadhesion properties which were further confirmed with the intestinal permeation study as well as confocal microscopy. The study revealed higher permeation of THQ-CPLNPs compared to neat THQ suspension (THQ-S). Moreover, in vivo gastric irritation study revealed good compatibility of THQ-CPLNPs with the gastric mucosa. Furthermore, pharmacokinetic results depicted -3.53-fold improved oral bioavailability of THQ from THQ-CPLNPs than THQ-S. Therefore, from the findings, it was concluded that the prepared polymeric NPs could be an effective delivery system for improved oral bioavailability of THQ. [ABSTRACT FROM AUTHOR]

• TNBC represents the most aggressive phenotype of breast cancer. • Conventional therapy prescribed for breast cancer is not effective in treatment of TNBC. • Specific therapeutic targets must be identified in TNBC. • The PI3K/Akt/Mtor (PAM) pathway is an important signaling pathway of TNBC. • Drug molecules targeting the PAM pathway could emerge as promising therapeutics. Triple-negative breast cancer (TNBC) is a highly malignant subtype of breast cancer associated with poor prognosis. Although conventional chemotherapy regimens have shown some effectiveness in early TNBC cases, the outcome in advanced stages is poor. The PI3K/AKT/mTOR pathway is one of the important and active pathways involved in chemoresistance and survival of TNBC. This pathway is speculated to play an important part in malignant transformation and has been considered as a potential molecular target for the design of therapeutic agents to treat TNBC. This review discusses the potentials and drug discovery perspectives of PI3K/AKT/mTOR as a therapeutic target for effective management of TNBC with anticipated challenges. [ABSTRACT FROM AUTHOR]

Nanogel is a promising drug delivery approach to improve the pharmacokinetics and pharmacodynamic prospect of phytopharmaceuticals. In the present review, phytopharmaceuticals with astonishing therapeutic utilities are being explored. However, their in vivo delivery is challenging, owing to poor biopharmaceutical attributes that impact their drug release profile, skin penetration, and the reach of optimal therapeutic concentrations to the target site. Nanogel and its advanced version in the form of nanoemulgel (oil-in-water nanoemulsion integrated gel matrix) offer better therapeutic prospects than other conventional counterparts for improving the biopharmaceutical attributes and thus therapeutic efficacy of phytopharmaceuticals. Nanoemulgel-loaded phytopharmaceuticals could substantially improve permeation behavior across skin barriers, subsequently enhancing the delivery and therapeutic effectiveness of the bioactive compound. Furthermore, the thixotropic characteristics of polymeric hydrogel utilized in the fabrication of nanogel/nanoemulgel-based drug delivery systems have also imparted improvements in the biopharmaceutical attributes of loaded phytopharmaceuticals. This formulation approach is about to be rife in the coming decades. Thus, the current review throws light on the recent studies demonstrating the role of nanogels in enhancing the delivery of bioactive compounds for treating various disease conditions and the challenges faced in their clinical translation. [ABSTRACT FROM AUTHOR]

The clinical application of phytochemicals such as thymoquinone (THQ) is restricted due to their limited aqueous solubility and oral bioavailability. Developing mucoadhesive nanocarriers to deliver these natural compounds might provide new hope to enhance their oral bioavailability. Herein, this investigation aimed to develop THQ-loaded lipid-polymer hybrid nanoparticles (THQ-LPHNPs) based on natural polymer chitosan. THQ-LPHNPs were fabricated by the nanoprecipitation technique and optimized by the 3-factor 3-level Box–Behnken design. The optimized LPHNPs represented excellent properties for ideal THQ delivery for oral administration. The optimized THQ-LPHNPs revealed the particles size (PS), polydispersity index (PDI), entrapment efficiency (%EE), and zeta potential (ZP) of <200 nm, <0.25, >85%, and >25 mV, respectively. THQ-LPHNPs represented excellent stability in the gastrointestinal milieu and storage stability in different environmental conditions. THQ-LPHNPs represented almost similar release profiles in both gastric as well as intestinal media with the initial fast release for 4 h and after that a sustained release up to 48 h. Further, the optimized THQ-LPHNPs represent excellent mucin binding efficiency (>70%). Cytotoxicity study revealed much better anti-breast cancer activity of THQ-LPHNPs compared with free THQ against MDA-MB-231 and MCF-7 breast cancer cells. Moreover, ex vivo experiments revealed more than three times higher permeation from the intestine after THQ-LPHNPs administration compared to the conventional THQ suspension. Furthermore, the THQ-LPHNPs showed 4.74-fold enhanced bioavailability after oral administration in comparison with the conventional THQ suspension. Therefore, from the above outcomes, mucoadhesive LPHNPs might be suitable nano-scale carriers for enhanced oral bioavailability and therapeutic efficacy of highly lipophilic phytochemicals such as THQ. [ABSTRACT FROM AUTHOR]

Early detection, right therapeutic intervention, and simultaneous effectiveness mapping are considered the critical factors in successful cancer therapy. Nevertheless, these factors experience the limitations of conventional cancer diagnostics and therapeutics delivery approaches. Along with providing the targeted therapeutics delivery, advances in nanomedicines have allowed the combination of therapy and diagnostics in a single system (called cancer theranostics). This paper discusses the progress in the pre-clinical and clinical development of therapeutics, diagnostics, and theranostics cancer nanomedicines. It has been well evident that compared to the overabundance of works that claimed success in pre-clinical studies, merely 15 and around 75 cancer nanomedicines are approved, and currently under clinical trials, respectively. Thus, we also brief the critical bottlenecks in the successful clinical translation of cancer nanomedicines. [ABSTRACT FROM AUTHOR]

The excellent therapeutic potential of a variety of phytochemicals in different diseases has been proven by extensive studies throughout history. However, most phytochemicals are characterized by a high molecular weight, poor aqueous solubility, limited gastrointestinal permeability, extensive pre-systemic metabolism, and poor stability in the harsh gastrointestinal milieu. Therefore, loading of these phytochemicals in biodegradable and biocompatible nanoparticles (NPs) might be an effective approach to improve their bioactivity. Different nanocarrier systems have been developed in recent decades to deliver phytochemicals. Among them, NPs based on chitosan (CS) (CS-NPs), a mucoadhesive, non-toxic, and biodegradable polysaccharide, are considered the best nanoplatform for the oral delivery of phytochemicals. This review highlights the oral delivery of natural products, i.e., phytochemicals, encapsulated in NPs prepared from a natural polymer, i.e., CS, for improved bioavailability and bioactivity. The unique properties of CS for oral delivery such as its mucoadhesiveness, non-toxicity, excellent stability in the harsh environment of the GIT, good solubility in slightly acidic and alkaline conditions, and ability to enhance intestinal permeability are discussed first, and then the outcomes of various phytochemical-loaded CS-NPs after oral administration are discussed in detail. Furthermore, different challenges associated with the oral delivery of phytochemicals with CS-NPs and future directions are also discussed. [ABSTRACT FROM AUTHOR]