Fabrication of TPGS decorated Etravirine loaded lipidic nanocarriers as a neoteric oral bioavailability enhancer for lymphatic targeting.

Etravirine (ERVN) is a potential NNRTI (non-nucleoside reverse transcriptase inhibitor) in treating HIV infection. It possesses extremely low oral bioavailability. The present research aims to optimize the formulation and characterization of TPGS-enriched ERVN-loaded lipid-based nanocarriers (NLCs) for HIV-infected patients. The formulation, ERVN-TPGS-NLCs, was optimized by central composite rotational design using a modified-solvent emulsification process. Various characterization parameters of NLCs were evaluated, including globule size of 121.56 ± 2.174 nm, PDI of 0.172 ± 0.042, the zeta potential of - 7.32 ± 0.021 mV, %EE of 94.42 ± 8.65% of ERVN and %DL was 8.94 ± 0.759% of ERVN and spherical shape was revealed by TEM. PXRD was also performed to identify the crystallinity of the sample. In-vitro drug release showed % a cumulative drug release of 83.72 ± 8.35% at pH 1.2 and 90.61 ± 9.11% at pH 6.8, respectively, whereas the % cumulative drug release from drug suspension (ERVN-S) was found to be 21.13 ± 2.01% at pH 1.2 and 24.84 ± 2.51 at pH 6.8 at the end of 48 h. Further, the intestinal permeation study and confocal microscope showed approximately three-fold and two-fold increased permeation in ERVN-TPGS-NLCs and ERVN-NLCs across the gut sac compared to ERVN-S. Hemolysis compatibility and lipolysis studies were performed to predict the in-vivo fate of the formulation. The pharmacokinetic study revealed a 3.13-fold increment in the relative bioavailability, which agrees with the ex-vivo studies, and lymphatic uptake was validated by using cycloheximide along with designed formulation, which showed the impact of lymphatic uptake in AUC. This study ensures that ERVN-TPGS-NLCs take lymphatic uptake to minimize the first-pass metabolism followed by improved oral bioavailability of ERVN. Thus, the enhanced bioavailability of ERVN can reduce the high dose of ERVN to minimize the adverse effects related to dose-related burden.

Transdermal Nutraceuticals Delivery System for CNS Disease.

Herbal medicines are being used by humans since the oldest civilizations and have been an integral part of traditional and alternative medicines. In recent times, pharmaceutical and biomedical scientists are taking interest in developing nutraceutical-based medicines to overcome the side effects and adverse drug reactions caused by allopathic medicines. Nutraceuticals have started occupying the global market. Nutraceuticals have gained widespread acceptance due to their efficacy in treating difficult to treat diseases, low toxicity, low cost, easy accessibility, etc. Safety and efficacy are other important factors in the commercialization process of nutraceuticals. Different novel advanced drug delivery systems have been constantly studied to improve the efficacy and bioavailability of medicines obtained from herbal sources. The transdermal drug delivery system provides a potent alternative to the conventional method of using nutraceuticals. The development of transdermal system-based nutraceuticals could provide the advantage of enhanced bioavailability, improved solubility, bypass of the first-pass metabolism, and targeted delivery of drugs in brain-related disorders. It additionally provides the advantage of being non-invasive. This article reviews the potential effects of various nutraceuticals in brain-related disorders as well as trends in transdermal nano-systems to deliver such nutraceuticals. We have also focused on advantages, applications as well as recent United States-based patents which emphasize emerging interest towards transdermal nutraceuticals in brain disorders.

Recent patents and a market overview on green or bio-based solvents for chromatographic analysis: a review.

Green solvents (GS) in chromatography originate from green chemistry. Therefore, using GSs in liquid chromatographic analysis to separate drugs and chemicals is an emerging approach to reduce hazardous chemicals in nature. The Orbit Intelligence database was used to conduct a strategic patent search for peer-reviewed patents on GSs as a mobile phase for chromatographic analysis. This article reported numerous approaches for encouraging GSs such as ethanol, butanol, esters, polyethylene glycol, supercritical fluids and nonionic surfactants to analyze drugs or compounds. The main aim of this article is to explore the patented GSs for chromatographic analysis and forecasting of the GSs that encourage industries to shift from hazardous to GSs.

An in-depth analysis of novel combinatorial drug therapy via nanocarriers against HIV/AIDS infection and their clinical perspectives: a systematic review.

Introduction: Conventional antiretroviral therapy against HIV infections is threatening to become outdated due to the low chemical, physical, biological, and pharmacokinetic characteristics of therapeutic molecules, followed by the high chance of emergence of drug resistance. Considering the co-encapsulation of multi-infection agents in a single nanocarrier is emerging to offer various benefits such as synergistic action, improved therapeutic efficacy, reduced drug resistance development, patient compliance, and economical therapy.Areas covered: A systematic review of nano-based combinatorial drug therapy was performed using various databases including Scopus, PubMed, Google Scholar, and Science Direct between 2000 and 2020. The search set was screened as per the inclusion and exclusion criteria, followed by 46 scientific articles and seven clinical studies selected for in-depth analysis.Expert opinion: There has been an immense effort to analyze the mechanism of HIV infection to develop a promising therapeutic approach, although the aim of complete prevention has not been succeeded yet. The key finding is to overcome the challenges associated with conventional therapy by the combinatorial drug in a single nanoformulation, which holds great potential for impact in the management of HIV infection.

Recent Patents, Regulatory Issues, and Toxicity of Nanoparticles in Neuronal Disorders.

BACKGROUND: Form last few decades, nanoparticles have witnessed breakthroughs in the treatment of neurological disorders due to their unique physiochemical properties, which make them an effective drug delivery system. However, there is not much information available on the toxicity of nanoparticles in neuronal disorders. The toxic effect of nanoparticles on brain disorders and their regulatory issues are the primary concerns of the healthcare industry. METHODS: A strategical literature search was performed on various bibliographic databases such as Scopus, PubMed, SciFinder, Google Scholar, Medline, Google Patent, Derwent Innovation, and Orbit Intelligence for retrieval of peer-reviewed articles and patents on regulatory issues and toxicity of nanoparticles in neuronal disorders for last decade. The relevant hits of articles and patents were analyzed, and citation search for the relevant documents was carried out. RESULTS: The literature documents have been summarized regarding the existing regulatory issues and toxicity of nanoparticles on neuronal disorders with a focus on the detailed mechanism of the developmental toxicity of nanoparticles. The focus of this report is to emphasize the negative effects of nanoparticle on neuronal disorders, which may partially contribute to the management of toxicity of nanoparticles. CONCLUSION: Although nanoparticles have unique physical and chemical properties that explain the broad range of application for the central nervous system, they can also manifest neurotoxic effects due to cell necrosis, generation of free radicals, immune responses and neuroinflammation. Thus, this review highlights risk assessment, safety regulations and regulatory guidelines of nanoparticles, which may reduce adverse reactions in humans and animals.

Nano Phytomedicine Based Delivery System for CNS Disease.

Herbal medicines are being used since ancient times and are an important part of the alternative and traditional medicinal system. In recent decades, scientists are embracing herbal medicines based on the fact that a number of drugs that are currently in use are derived directly or indirectly from plant sources. Moreover, herbal drugs have lesser side effects, albeit are potentially strong therapeutic agents. The herbal medicine market is estimated to be around US $62 billion globally. Herbal medicine has gained widespread acceptance due to its low toxicity, low cost, ease of accessibility and efficacy in treating difficult diseases. Safety and efficacy are another important factors in the commercialization process of herbal medicines. Nanotechnology has been shown to be potentially effective in improving the bioactivity and bioavailability of herbal medicines. Development of nano-phytomedicines (or by reducing the size of phytomedicine), attaching polymers with phytomedicines and modifying the surface properties of herbal drugs, have increased the solubility, permeability and eventually the bioavailability of herbal formulations. Novel formulations such as niosomes, liposomes, nanospheres, phytosomes etc., can be exploited in this area. This article reviews herbal medicines, which have prominent activity in the Central Nervous System (CNS) disorders and reported nano-phytomedicines based delivery systems.

Quantum Dots: Next Generation of Smart Nano-Systems.

BACKGROUND: The amalgamation of biological sciences with nano stuff has significantly expedited the progress of biological strategies, greatly promoting practical applications in biomedical fields. OBJECTIVE: With distinct optical attributes (e.g., robust photostability, restricted emission spectra, tunable broad excitation, and high quantum output), fluorescent quantum dots (QDs) have been feasibly functionalized with manageable interfaces and considerably utilized as a new class of optical probe in biological investigations. METHODS: In this review article, we structured the current advancements in the preparation methods and attributes of QDs. Furthermore, we extend an overview of the outstanding potential of QDs for biomedical research and radical approaches to drug delivery. CONCLUSION: Notably, the applications of QDs as smart next-generation nanosystems for neuroscience and pharmacokinetic studies have been explained. Moreover, recent interests in the potential toxicity of QDs are also apprised, ranging from cell investigations to animal studies.

3D Printing Methods for Pharmaceutical Manufacturing: Opportunity and Challenges.

BACKGROUND: A recently FDA approved 3D printed drug is paving a path for new pharmaceutical manufacturing era. The 3D printing is a novel approach of producing 3D pharmaceuticals from digital designs, in a layer-by-layer fashion. However, traditional manufacturing of drug products is being carried out from decades with well-established manufacturing processes and with well approved regulatory guidelines but these processes are too obsolete in concern of process aptitude and manufacturing flexibility. On the other hand, 3D printing provides a competitive flexibility in terms of personalized drug dosage forms with complex geometries that will be made on-demand with desired drug release kinetics, hence providing the formulator a substantial provision of improvising the safety and efficacy of the drugs. Furthermore, this novel 3D technology allows tailoring of composite tissue scaffolds and sample models for characterization that closely mimic in-vivo simulations. Nevertheless, certain limitations are there in terms of regulatory aspects hindering the launch of 3DP products in the market. METHODS: Exhaustive search were made on Google Scholar and PubMed databases concerning 3-D printing methods, drug delivery applications, and past to present evolution of personalized medicine. RESULTS: Although a high magnitude of progress have been made on 3-D printing techniques in a short span of time, still inkjet, nozzle-based deposition, stereolithography and selective laser sintering techniques are the most popular ones. Their application is adapted in the fabrication of tablets, implants, polypills and nanoparticles. CONCLUSION: 3D printing is revolutionizing the pharma expectations towards customized medicines but still there is a need to explore the aspects of cost, flexibility and bioequivalence. The present review provides a comprehensive account of various 3D printing technologies and highlights the opportunities and key challenges of 3D printing relevant to pharmaceuticals.

A Combinatorial Statistical Design Approach to Optimize the Nanostructured Cubosomal Carrier System for Oral Delivery of Ubidecarenone for Management of Doxorubicin-Induced Cardiotoxicity: In Vitro-In Vivo Investigations.

Present work aims to optimize and characterize orally administered, ubidecarenone (UDC)-loaded glycerylmonooleate-based cubosome (GCBMs) and phytantriol based cubosomes (PCBMs) for effective management of doxorubicin-induced cardiotoxicity and to enhance bioavailability of UDC. Formulations optimized using statistical hybrid-design approach exhibited particle size of 152.0 ± 1.78 and 248.8 ± 1.83 nm, polydispersity index of 0.183 ± 0.021 and 0.225 ± 0.018 with zeta potential of -26.8 ± 0.76 and -23.3 ± 0.22 mV and percentage entrapment efficiency (% EE) of 92.3 ± 4.99% and 94.7 ± 5.67%, for GCBMs and PCBMs, respectively. High-resolution transmission electron microscopy revealed agreement with the particle size and shows the discrete cubic geometry of particles, while small-angle X-ray scattering analysis confirmed the primitive (Im3m) and diamond (Pn3m) type crystalline cubic self-assemble structure of the particles. The comparative bioavailability profiles of UDC from GCBMs and PCBMs (AUC0→∞ = 19,546.8 ± 512.88 ng·h/L for GCBMs and 27,961.99 ± 602.46 ng·h/L for PCBMs) were approximately 6.5- and 7.0-fold higher than that of UDC suspension (AUC0→∞ = 3132.806 ± 405.44 ng·h/L). Cardioprotective assessment showed a significant increase in superoxide dismutase and ß-glutathione peroxidase levels, while a decrease in the level of catalase, creatine kinase-MB isoenzyme, lactate dehydrogenase, and lipid peroxidation was observed in animals pre-treated with developed CBMs. Histopathology studies revealed no significant damage, infiltrated cells, and signs of fibrosis in the CBM-treated groups.

Magnetic Nanoparticles: A Review on Stratagems of Fabrication an d its Biomedical Applications.

BACKGROUND: The aim of this review is to provide an insight to the underlying biomedical applications of magnetic nanoparticles (MNPs). METHODS: The most specific characteristic of MNPs is their response to an applied magnetic force, and this property of MNPs has been utilized in applications such as diagnosis of diseases, drug delivery and drug targeting. Currently, MNPs have attracted great attention because of their potential as contrast agents for magnetic resonance imaging (MRI) and heat mediators for cancer therapy (hyperthermia). RESULTS: Furthermore, the MNPs are also being used to achieve targeted delivery of biological molecules. Nowadays cancer is one of the biggest challenges and our goal is not only to improve the therapeutic outcome, but also to improve the methods of treatment along with the minimum adverse effect. Some suitable conclusions have been quoted on the precise synthesis approaches by focusing the mechanism of MNPs and new modification made on the production of these nanoparticles. CONCLUSION: In this review diverse biomedical application of MNPs were also addressed and patents related remarks also made from the literature.

Development and validation of stability indicating liquid chromatographic (RP-HPLC) method for estimation of ubidecarenone in bulk drug and formulations using quality by design (QBD) approach

ABSTRACT A novel, accurate, precise and economical stability indicating Reverse Phase-High Performance Liquid Chromatography (RP-HPLC) method, was developed and validated for the quantitative determination of ubidecarenone (UDC) in bulk drug, UDC marketed formulation and UDC loaded cubosomes (CBMs) nanocarriers through Response surface methodology (RSM) design with three factors and three levels was performed to optimize the chromatographic variables followed by forced degradation studies of UDC were performed to detect degradation peak. RP-HPLC separation was achieved using mobile phase consisting of Acetonitrile:Tetrahydrofuran:Deionised water in the ratio 55:42:3 and a flow rate of 1.0 mL/min was optimized with a standard retention time (Rt) of 2.15 min, through experiment. The method was found linear in the concentration range of 5-100 µg/mL with a regression coefficient of 0.999. The limit of detection (LOD) and limit of quantification (LOQ) were found to be 3.04 µg/mL and 9.11 µg/mL, respectively.

A review on the strategies for oral delivery of proteins and peptides and their clinical perspectives.

In the modern world, a number of therapeutic proteins such as vaccines, antigens, and hormones are being developed utilizing different sophisticated biotechnological techniques like recombinant DNA technology and protein purification. However, the major glitches in the optimal utilization of therapeutic proteins and peptides by the oral route are their extensive hepatic first-pass metabolism, degradation in the gastrointestinal tract (presence of enzymes and pH-dependent factors), large molecular size and poor permeation. These problems can be overcome by adopting techniques such as chemical transformation of protein structures, enzyme inhibitors, mucoadhesive polymers and permeation enhancers. Being invasive, parenteral route is inconvenient for the administration of protein and peptides, several research endeavors have been undertaken to formulate a better delivery system for proteins and peptides with major emphasis on non-invasive routes such as oral, transdermal, vaginal, rectal, pulmonary and intrauterine. This review article emphasizes on the recent advancements made in the delivery of protein and peptides by a non-invasive (peroral) route into the body.