BBD Driven Fabrication of Hydroxyapatite Engineered Risedronate Loaded Thiolated Chitosan Nanoparticles and Their In Silico, In Vitro, and Ex Vivo Studies.

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).

Statistically Optimized Tacrolimus and Thymoquinone Co-Loaded Nanostructured Lipid Carriers Gel for Improved Topical Treatment of Psoriasis.

The aim of this investigation was to develop and analyze a tacrolimus and thymoquinone co-loaded nanostructured lipid carriers (TAC-THQ-NLCs)-based nanogel as a new combinatorial approach for the treatment of psoriasis. The NLCs were formulated by an emulsification-solvent-evaporation technique using glyceryl monostearate, Capryol 90 (oil), and a mixture of Tween 80 and Span 20 as a solid lipid, liquid lipid, and surfactant, respectively. Their combination was optimized using a three-factor and three-level Box-Behnken design (33-BBD). The optimized TAC-THQ-NLCs were observed to be smooth and spherical with a particle size of 144.95 ± 2.80 nm, a polydispersity index of 0.160 ± 0.021, a zeta potential of -29.47 ± 1.9 mV, and an entrapment efficiency of >70% for both drugs. DSC and PXRD studies demonstrated the amorphous state of TAC and THQ in the lipid matrix of the NLCs. An FTIR analysis demonstrated the excellent compatibility of the drugs with the excipients without interactions. The TAC-THQ-NLC-based nanogel (abbreviated as TAC-THQ-NG) exhibited a good texture profile and good spreadability. The in vitro release study demonstrated a sustained drug release for 24 h from the TAC-THQ-NG that followed the Korsmeyer-Peppas kinetic model with a Fickian diffusion mechanism. Moreover, the TAC-THQ-NG revealed significantly higher dose-dependent toxicity against an HaCaT cell line compared to a TAC-THQ suspension gel (abbreviated as TAC-THQ-SG). Furthermore, the developed formulations demonstrated antioxidant activity comparable to free THQ. Confocal microscopy revealed improved permeation depth of the dye-loaded nanogel in the skin compared to the suspension gel. Based on these findings, it was concluded that TAC-THQ-NG is a promising combinatorial treatment approach for psoriasis.

Polymer-lipid hybrid nanoparticles of exemestane for improved oral bioavailability and anti-tumor efficacy: An extensive preclinical investigation.

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.

Nanogels as Potential Delivery Vehicles in Improving the Therapeutic Efficacy of Phytopharmaceuticals.

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.

Development of cannabidiol nanoemulsion for direct nose to brain delivery: statistical optimization,in vitroandin vivoevaluation.

Cannabidiol (CBD) is a prescribed drug for epilepsy but has low oral bioavailability and gastric instability. Because of the direct link between the nasal cavity and the central nervous system, intranasal administration of CBD as nanoemulsions which are the small sized lipid carriers seem to improve the bioavailability. CBD-nanoemulsions (NEs) were made using Capryol 90, Tween 80, and Transcutol P as oil, surfactant, and co-surfactant, respectively, following aqueous titration approach. Then, using the Box-Behnken design, CBD-NE was statistically optimised for the selection of desirable excipient concentrations in order to create the optimal CBD-NE formulation. As independent variables in the statistical design, Capryol 90 (oil; coded asA), Tween 80 (surfactant; coded asB), and Transcutol P (co-surfactant; coded asC) were used. The dependent variables were droplet size (DS; coded asR1) and polydispersity index (PDI; coded asR2). The average DS, PDI, and the zeta potential of the optimized CBD-NEs were observed to be 88.73 ± 2.67 nm, 0.311 ± 0.015, and -2.71 ± 0.52 mV respectively. Pure CBD and lyophilized CBD-NEFourier-transform infraredspectra demonstrated no physicochemical interaction between excipients and the drug. Furthermore, differential scanning calorimetry and x-ray diffraction measurements revealed the amorphous CBD in the NE. As compared to pure CBD, the optimised CBD-NE showed considerably betterin vitrodrug release as well asex vivonasal permeability. The drug targeting efficiency and direct transport percentage of the optimised CBD-NEs were found to be 419.64% and 76.17%, respectively, in this research. Additionally, pharmacokinetic investigations after intranasal administration of CBD-NE revealed considerably higher drug concentrations in the brain with better brain targeting efficiency. As a result, the development of CBD-NE may be an excellent alternative for better intranasal delivery.

Harnessing Lipid Polymer Hybrid Nanoparticles for Enhanced Oral Bioavailability of Thymoquinone: In Vitro and In Vivo Assessments.

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.

Receptor-Targeted Surface-Engineered Nanomaterials for Breast Cancer Imaging and Theranostic Applications.

Breast cancer is one of the most frequently diagnosed cancers in women and the major cause of worldwide cancer-related deaths among women. Various treatment strategies including conventional chemotherapy, immunotherapy, gene therapy, gene silencing and deliberately engineered nanomaterials for receptor mediated targeted delivery of anticancer drugs, antibodies, and small-molecule inhibitors, etc are being investigated by scientists to combat breast cancer. Smartly designed/fabricated nanomaterials are being explored to target breast cancer through enhanced permeation and retention effect; and also, being conjugated with suitable ligand for receptor-mediated endocytosis to target breast cancer for diagnostic, and theranostic applications. These receptor-targeted nanomedicines have shown efficacy to target specific tumor tissue/cells abstaining the healthy tissues/cells from cytotoxic effect of anticancer drug molecules. In the last few decades, theranostic nanomedicines have gained much attention among other nanoparticle systems due to their unique ability to deliver chemotherapeutic as well as diagnostic agents, simultaneously. Theranostic nanomaterials are emerging as novel paradigm with ability for concurrent delivery of imaging (with contrasting agents), targeting (with biomarkers), and anticancer therapeutics with one delivery system (as cancer theranostics) and can transpire as promising strategy to overcome various hurdles for effective management of breast cancer including its most aggressive form, triple-negative breast cancer.

Current Insight into the Therapeutic Potential of Phytocompounds and their Nanoparticle-Based Systems for Effective Management of Lung Cancer.

Lung cancer is the second most common cancer and the primary cause of cancer-related death in both men and women worldwide. Due to diagnosis at an advanced stage, it is associated with high mortality in the majority of patients. At present, various treatment approaches are available, such as chemotherapy, surgery, and radiotherapy, but all these approaches usually cause serious side effects like degeneration of normal cells, bone marrow depression, alopecia, extensive vomiting, etc. To overcome the aforementioned problems, researchers have focused on the alternative therapeutic approach in which various natural compounds are reported, which possessed anti-lung cancer activity. Phytocompounds exhibit their anti lung cancer activity via targeting various cell-signaling pathways, apoptosis and cell cycle arrest, and by regulating antioxidant status and detoxification. Apart from the excellent anti-cancer activity, clinical administration of phytocompounds is confined because of their high lipophilicity and low bioavailability. Therefore, researchers show their concern in the development of a stable, safe and effective approach of treatment with minimal side effects by the development of nanoparticle-based delivery of these phytocompounds to the target site. Targeted delivery of phytocompound through nanoparticles overcomes the aforementioned problems. In this article, the molecular mechanism of phytocompounds, their emerging combination therapy, and their nanoparticles-based delivery systems in the treatment of lung cancer have been discussed.

Receptor-Mediated Targeted Delivery of Surface-ModifiedNanomedicine in Breast Cancer: Recent Update and Challenges.

Breast cancer therapeutic intervention continues to be ambiguous owing to the lack of strategies for targeted transport and receptor-mediated uptake of drugs by cancer cells. In addition to this, sporadic tumor microenvironment, prominent restrictions with conventional chemotherapy, and multidrug-resistant mechanisms of breast cancer cells possess a big challenge to even otherwise optimal and efficacious breast cancer treatment strategies. Surface-modified nanomedicines can expedite the cellular uptake and delivery of drug-loaded nanoparticulate constructs through binding with specific receptors overexpressed aberrantly on the tumor cell. The present review elucidates the interesting yet challenging concept of targeted delivery approaches by exploiting different types of nanoparticulate systems with multiple targeting ligands to target overexpressed receptors of breast cancer cells. The therapeutic efficacy of these novel approaches in preclinical models is also comprehensively discussed in this review. It is concluded from critical analysis of related literature that insight into the translational gap between laboratories and clinical settings would provide the possible future directions to plug the loopholes in the process of development of these receptor-targeted nanomedicines for the treatment of breast cancer.

Recent Advancement in Chitosan-Based Nanoparticles for Improved Oral Bioavailability and Bioactivity of Phytochemicals: Challenges and Perspectives.

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.

Exemestane encapsulated polymer-lipid hybrid nanoparticles for improved efficacy against breast cancer: optimization,in vitrocharacterization and cell culture studies.

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 33Box-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 vitrorelease 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.

Advancement in design of nanostructured lipid carriers for cancer targeting and theranostic application.

BACKGROUND: 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. SCOPE OF REVIEW: 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. MAJOR CONCLUSIONS: 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. GENERAL SIGNIFICANCE: 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.

Thymoquinone-entrapped chitosan-modified nanoparticles: formulation optimization to preclinical bioavailability assessments.

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 ± 6.46 nm, 0.179 ± 0.012, and +21.36 ± 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.

Molecular Targets and Nanoparticulate Systems Designed for the Improved Therapeutic Intervention in Glioblastoma Multiforme.

Glioblastoma multiforme (GBM) is the most aggressive and fatal CNS related tumors, which is responsible for about 4% of cancer-related deaths. Current GBM therapy includes surgery, radiation, and chemotherapy. The effective chemotherapy of GBM is compromised by two barriers, i. e., the blood-brain barrier (BBB) and the blood tumor barrier (BTB). Therefore, novel therapeutic approaches are needed. Nanoparticles are one of the highly efficient drug delivery systems for a variety of chemotherapeutics that have gained massive attention from the last three decades. Perfectly designed nanoparticles have the ability to cross BBB and BTB and precisely deliver the chemotherapeutics to GBM tissue/cells. Nanoparticles can encapsulate both hydrophilic and lipophilic drugs, genes, proteins, and peptides, increase the stability of drugs by protecting them from degradation, improve plasma half-life, reduce adverse effects and control the release of drugs/genes at the desired site. This review focussed on the different signaling pathways altered in GBM cells to understand the rationale behind selecting new therapeutic targets, challenges in the drug delivery to the GBM, various transport routes in brain delivery, and recent advances in targeted delivery of different drug and gene loaded various lipidic, polymeric and inorganic nanoparticles in the effective management of GBM.

Progress of Cancer Nanotechnology as Diagnostics, Therapeutics, and Theranostics Nanomedicine: Preclinical Promise and Translational Challenges.

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.

Optimization to development of chitosan decorated polycaprolactone nanoparticles for improved ocular delivery of dorzolamide: In vitro, ex vivo and toxicity assessments.

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.

Nanostructured Lipid Carriers (NLCs): Nose-to-Brain Delivery and Theranostic Application.

BACKGROUND: Nanostructured lipid carriers (NLCs) are in high demand in the existing pharmaceutical domain due to its high versatility. It is the newer generation of lipid nanoparticulate systems having a solid matrix and greater stability at room temperature. OBJECTIVE: To review the evidence related to the current state of the art of the NLCs system and its drug delivery perspectives to the brain. METHODS: Scientific data search, review of the current state of the art and drug delivery perspectives to the brain for NLCs were undertaken to assess the applicability of NLCs in the management of neurological disorders through an intranasal route of drug administration. RESULTS: NLCs are designed to fulfill all the industrial needs like simple technology, low cost, scalability, and quantifications. Biodegradable and biocompatible lipids and surfactants used for NLCs have rendered them acceptable from regulatory perspectives as well. Apart from these, NLCs have unique properties of high drug payload, modulation of drug release profile, minimum drug expulsion during storage, and incorporation in various dosage forms like gel, creams, granules, pellets, powders for reconstitution and colloidal dispersion. Ease of surface- modification of NLCs enhances targeting efficiency and reduces systemic toxicity by providing site-specific delivery to the brain through the intranasal route of drug administration. CONCLUSION: The present review encompasses the in-depth discussion over the current state of the art of NLCs, nose-to-brain drug delivery perspectives, and its theranostic application as useful tools for better management of various neurological disorders. Further, pharmacokinetic consideration and toxicity concern is also discussed specifically for the NLCs system exploited in nose-to-brain delivery.

Therapeutic Nanoemulsion: Concept to Delivery.

Nanoemulsions (NEs) or nanometric-scaled emulsions are transparent or translucent, optically isotropic and kinetically stable heterogeneous system of two different immiscible liquids namely, water and oil stabilized with an amphiphilic surfactant having droplet size ranges up to 100 nm. They offer a variety of potential interests for certain applications: improved deep-rooted stability; excellent optical clarity; and, enhanced bioavailability due to its nanoscale of particles. Though there is still comparatively narrow insight apropos design, development, and optimization of NEs, which mainly stems from the fact that conventional characteristics of emulsion development and stabilization only partly apply to NEs. The contemporary article focuses on the nanoemulsion dosage form journey from concept to key application in drug delivery. In addition, industrial scalability of the nanoemulsion, as well as its presence in commercial and clinical practice, are also addressed.

Nanomedicines in Diagnosis and Treatment of Cancer: An Update.

Nanomedicine has revolutionized the field of cancer detection and treatment by enabling the delivery of imaging agents and therapeutics into cancer cells. Cancer diagnostic and therapeutic agents can be either encapsulated or conjugated to nanosystems and accessed to the tumor environment through the passive targeting approach (EPR effect) of the designed nanomedicine. It may also actively target the tumor exploiting conjugation of targeting moiety (like antibody, peptides, vitamins, and hormones) to the surface of the nanoparticulate system. Different diagnostic agents (like contrast agents, radionuclide probes and fluorescent dyes) are conjugated with the multifunctional nanoparticulate system to achieve simultaneous cancer detection along with targeted therapy. Nowadays targeted drug delivery, as well as the early cancer diagnosis is a key research area where nanomedicine is playing a crucial role. This review encompasses the significant recent advancements in drug delivery as well as molecular imaging and diagnosis of cancer exploiting polymer-based, lipid-based and inorganic nanoparticulate systems.

Polymer-Lipid Hybrid Nanoparticles: A Next-Generation Nanocarrier for Targeted Treatment of Solid Tumors.

At present, cancer is the most deadly disease and one of the most common causes of death worldwide providing different obstacles to chemotherapy including non-specific biodistribution of chemotherapeutic drugs, dose-related adverse effects, development of metastasis and chemoresistance. Nanoparticle-based targeted delivery of chemotherapeutics gained enormous attention in the treatment of solid tumors as they provide many significant advantages including prolonged drug release, enhanced systemic half-life, decreased toxicity and targeted drug delivery. Polymer-lipid hybrid nanoparticles (PLHNPs) are the most effective nanoplatform that develop from building blocks of polymers and lipids. PLHNPs combine the unique advantages of both lipid-based nanoparticles as well as polymeric nanoparticles. PLHNPs integrate biocompatible polymers and biomimetic lipids in their architecture, which imparts PLHNPs with wide versatility for delivering chemotherapeutic drugs of different physicochemical characteristics to their target site of action. The hybrid architecture of PLHNPs provides many exceptional advantages such as small particle size, encapsulation of more than one anticancer drugs, high drug loading capacity and modified drug release profile. Furthermore, the surface decoration of PLHNPs improves the therapeutic potential of the chemotherapeutic drug by selective targeting of tumor tissue and reduces the side effects by decreasing non-specific biodistribution. This review highlights the challenges in the treatment of solid tumors by using nanoparticles system, rationale and targeting strategies of PLHNPs in the targeted treatment of solid tumors, and current progress of PLHNPs in the management of different types of solid tumors.