Preparation of tripterygium glycoside nanoparticles and therapeutic effect on arthritis rats / 中国药理学通报

Aim To prepare tripterygium glycoside nanoparticles and probe into their therapeutic effect on collagen-induced arthritis ( CIA) rats. Methods Tripterygium glycosides polyglycoside nanoparticles were prepared by thin film dispersion method and their quality was assessed. The CIA model was established and drug intervention performed. The body weight, toe swelling degree and arthritis index were measured. The pathological changes of the organs, knee and ankle synovium were observed. The serum levels of kidney function and inflammatory cytokine expression were detected in rats. Results The prepared tripterygium wil-fordii polyglycoside nanoparticles were round particles with uniform distribution and stable properties under electron microscope. Compared with the model group, the swelling of the left and right toes of medication group significantly decreased (P < 0. 01), and the ar-thritis index markedly decreased ( P < 0. 01). Among them, the efficacy of the TG-NPs group was better than that of the TG group. Compared with the normal group, the indexes of heart, spleen, kidney and testis all significantly decreased (P <0. 05, P<0.01). TG-NPs group had a significantly reduced pathological ankle-joint injury in knee cartilage and increased apoptotic synovial cells. Compared with the model group, the serum levels of ALT and BUN and CRE in TG-NPs group were significantly lower (P < 0. 05 ), and IL-1β, TNF-α and IL-6 levels decreased significantly (P <0. 05). Conclusions TG-NPs have good therapeutic effect on CIA through induction of synovial cell apoptosis and decrease of the expression of inflammatory cytokines. By intravenous injection of blood circula-tion, slow and controlled release of drugs can be achieved, the first pass effect caused by oral drug can be avoided, the viscera toxicity can be reduced, which provides an experimental basis for the development of new nanoagents for the treatment of rheumatoid arthritis.

Metabolic regulation and drug target discovery researches in China: Progress and prospect / 中国临床药理学与治疗学

Metabolic regulation is an important mechanism by which organisms adapt to changes in the internal and external environment. Metabolic small molecules function as versatile messengers involved in signaling networks and organ crosstalk, which carries great implications for understanding physiological processes, revealing disease mechanisms and discovering drug targets. In this review, we present an overview of the main progresses in metabolic regulation and drug target discovery researches in China, and look forward to its future direction, which may provide a reference for the drug development endeavor based on metabolic regulation.

Applications of drug interaction study in new drug development and regulartory decision-making / 中国临床药理学与治疗学

Drug-drug interactions (DDI) change dose-response relationships, and may result in low efficacy or high toxicity, which are important considerations especially in medical practice with multiple-drug therapies. Predicting clinically significant drug interactions during new drug development is an important part of benefit and risk assessment in drug development and review. This article summarizes the purpose and significance of drug interactions in new drug development, the main content and precautions of DDI studies in vivo and in vitro. Drug interaction studies on novel drug approvals for 2020 in the National Medical Products Administration (NMPA) and US Food and Drug Administration (USFDA) are examined, respectively. It aims to provide reference for DDI studies and regulatory reviews in new drug development in our country.

On indirect actions of Chinese medicines and innovation of indirect-acting Chinese medicines / 中国中药杂志

The output of high level innovative Chinese medicines(CM) is very rare for a few years, which is in sharp contrast to the reality that antibody drugs, small molecular targeted therapy, antibody-drug conjugate and other innovative drugs have heavy investment and high yield. Acceleration for the research and development of innovative CM drugs obviously relies on breakthrough of the modes of thinking and methodology. Deeply influenced by the thinking of allopathic medicine in Western science system, the mainstream of current basic researches on CM is to find the components and their molecular mechanisms that can directly inhibit or antagonize the target in disease focal. However, it is difficult to explain the mechanism of the reported " active" components in many CMs, since their steady-state concentrations in disease focal are usually significantly lower than the effective concentrations of those components. Therefore, based on the original methodology of CM-systemism and harmonizing medicine, this paper proposed that the mechanism of action of CMs may not be limited to the direct antagonistic effect on the target in disease focal. Instead, it may involve indirect action through the intermediate substances across different organs or systems with a long-distance action pattern.A fundamentally break may be achieved when exploring the mechanism of action of CM active components from the perspective of indirect action. It may also change the thinking of allopathic medicine in the researches of CM and start a new innovative road for the development of indirect-acting CMs.

Bioactive Peptides from Marine Molluscs – A Review

Marine organisms make up approximately half of the total global biodiversity, with the Molluscacontaining the second largest number of species, including snails and bivalves. The marine environment is highly competitive, hostile and aggressive, which has led to the production of specific and potent bioactive compounds by the mollusca and their associated microorganisms, in a bid to protect themselves and ensure their survival. A diverse array of bioactive compounds can be isolated from the extracts of marine molluscs of which linear, cyclic, and conjugated peptides and depsipeptides form some of themost important bioactive compounds that have been well characterized and some of have already reached clinical trials or been approved for use as therapeutic agents and supplements. This review highlights some of the bioactive peptides that have been obtained from marine molluscs as well the challenges facing bioprospecting of valuable peptides from marine mollusc sources.

An introspection of quality of novel drug approvals by United States Food and Drug Administration

Background: United States Food and Drug Administration (FDA) is the fastest drug review agency in the world. FDA is responsible for protection of the public health by assuring that foods are safe, wholesome, sanitary and properly labelled. Approved Novel drugs are often innovative products that serve unmet medical needs or otherwise help to advance patient care.Methods: FDA novel drug approvals were analysed from calendar year (CY) 2012 to 2016 on the basis of three criteria i.e., impact, access and predictability. Impact measured on the basis of: percentage of novel drug approvals (a) first in class (b) for rare diseases. Access measured on the basis of: percentage of novel drug approvals (a) first cycle approval (b) approval in the U.S. before other countries and (c) percentage of priority reviews. Predictability measured by: the percentage of novel drug approvals that met the PDUFA goal dates for the application review.Results: Total number of novel drugs approved from CY 2012 to 2016 was 176 (average 35 novel drugs/ year). Impact of novel drug approvals: 40% were first in class and 39% were for rare diseases. Access of novel drug approvals: 84% were first cycle approval, 60% were approval in US before other countries, 51% priority reviews among novel drug approvals. Predictability of novel drug approvals: 97% approvals able to meet PDUFA goal dates for application review.Conclusions: Novel drug approvals during CY 2012-2016 had a high quality which is very much evident by their high impact, good access and high predictability.

Study of erythrocytes as a novel drug carrier for the delivery of artemether

Resealed erythrocytes have been explored in various dimensions of drug delivery, owing to their high biocompatibility and inability to initiate immune response. The present research was designed to evaluate the drug delivery potential of erythrocytes by loading a hydrophobic anti-malarial drug, Artemether. Three different loading techniques were applied to achieve maximum optimized drug loading. A HPLC method was validated for drug quantification in erythrocytes. The relatively high loading was achieved using hypotonic treatment was 31.39% as compared to other two methods. These, drug loaded erythrocytes were characterized for membrane integrity via ESR showing higher ESR values for drug loaded cells as compared to normal cells. Moreover, microscopic evaluation was done to observe morphological changes in erythrocytes after successful loading which showed swollen cells with slight rough surface as compared to smooth surface of normal cells. Drug release was studied for 8 h which showed more than 80% release within 3-7 h from erythrocytes treated with different hypotonic methods. Overall, the study revealed a potential application of erythrocytes in delivery of hydrophobic drugs using hypotonic treatment as compared to other methods.

Novel drug research and development ability in China: An international comparison and analysis / 中国卫生政策研究

Under the background of innovation-driven development and advanced biopharmaceutical innovative construction,this paper selects the indicators from three aspects:capital investment,talent resources and innovation output,and a comparative evaluation of the innovation drug R&D ability of China and the developed countries namely United States,Japan and Europe,as the basis to reveal the policy causes of the innovation ability discrepancies in China.The empirical results show that the total amount of funds invested in R&D of innovative drugs is increasing and the number of R&D personnel has become the scale.However,the investment intensity is still far from that of the developed countries,and the capital investment structure is also deficient of rationality.This is inseparable from the absence of preferential taxation policies,lack of high-level personnel training,environmental defects in production and research,and narrow coverage of health insurance policies.

Novel drug research and development ability in China: An international comparison and analysis / 中国卫生政策研究

Under the background of innovation-driven development and advanced biopharmaceutical innovative construction,this paper selects the indicators from three aspects:capital investment,talent resources and innovation output,and a comparative evaluation of the innovation drug R&D ability of China and the developed countries namely United States,Japan and Europe,as the basis to reveal the policy causes of the innovation ability discrepancies in China.The empirical results show that the total amount of funds invested in R&D of innovative drugs is increasing and the number of R&D personnel has become the scale.However,the investment intensity is still far from that of the developed countries,and the capital investment structure is also deficient of rationality.This is inseparable from the absence of preferential taxation policies,lack of high-level personnel training,environmental defects in production and research,and narrow coverage of health insurance policies.

A review on nanoparticles – preparation and evaluation parameters.

Nanotechnology defined as a tiny science. Design characterization, production and applications of structures, devices and systems by controlling shape and size at nanometer scale is refers to nanotechnology. Nanotechnology by which we can achieve better therapeutic action, better bioavailability and better patient compliance. Several nanoformulations are successfully used for brain delivery which includes nanoparticles system (polymeric/solid lipid), liposomes, dendrimer‟s, nanoemulsions, nanosuspension and ligand mediated nanosystems.Nanoparticles are defined as particulate dispersions or solid particles drug carrier that may or may not be biodegradable. Several techniques are used for preparation of nanoparticles like Solvent Evaporation, Double Emulsification method, Emulsions - Diffusion Method, Nanoprecipitation, Coacervation method, Salting Out Method, Dialysis and Supercritical fluid technology. Nanoparticles are subjected to several evaluation parameters such as yield of nanoparticles, Drug Content / Surface entrapment / Drug entrapment, Particle Size and Zeta Potential , Surface Morphology, Polydispersity index, In-vitro release Study, Kinetic Study, Stability of nanoparticles.

Research progress on local pharmacokinetics of novel drug delivery system of Chinese materia medica / 中草药

With rapid development of modern science and technology, much progress has been made in novel drug delivery system of Chinese materia medica (CMM), combined with new polymer materials and multidisciplinary knowledge. Compared with the traditional preparation, novel drug delivery system in drug distribution in vivo presented high selectivity. In addition, there was no clear correlation between drug concentration in blood and efficacy. Pharmacokinetic process in local target in effect should therefore be systematically investigated. In this article, the author reviewed the means and technology of local pharmacokinetic study on novel drug delivery system for CMM, as well as progress made, and further discussed the developmental issues and challenges.

Autologous stem cell transplantation for multiple myeloma in the era of new drugs / 中国肿瘤临床

Autologous stem cell transplantation (ASCT) is the standard frontline therapy for newly diagnosed multiple myeloma (MM) in patients younger than 65 years in the era of conventional chemotherapy. The use of novel drug-based chemotherapy in the in-duction, consolidation, and maintenance phases of chemotherapy has significantly improved the response rates of patients. Thus, wheth-er or not ASCT is still necessary in the era of new drugs has become controversial. Currently available data supported that ASCT should be the frontline therapy for qualified newly diagnosed MM patients and that new drugs may be applied before and after ASCT to further improve the response rate and prolong the progression-free survival of patients. Further prospective clinical trials should be conducted to clarify the role of ASCT in MM and optimize the treatment strategies involving ASCT in the era of new drugsto cure myeiona.

Research progress of novel drug gel / 药学实践杂志

The novel drug gel was a new formulation ,which was applied more and more in medicine field recently .The intelligent hydrogel ,liposome gels ,clathrate gels were summarized ,which could be provide reference for counterparts .

Bioavailability enhancers of herbal origin：An overview

Recently, the use of herbal medicines has been increased all over the world due to their therapeutic effects and fewer adverse effects as compared to the modern medicines. However, many herbal drugs and herbal extracts despite of their impressive in-vitro findings demonstrates less or negligible in-vivo activity due to their poor lipid solubility or improper molecular size, resulting in poor absorption and hence poor bioavailability. Nowadays with the advancement in the technology, novel drug delivery systems open the door towards the development of enhancing bioavailability of herbal drug delivery systems. For last one decade many novel carriers such as liposomes, microspheres, nanoparticles, transferosomes, ethosomes, lipid based systems etc. have been reported for successful modified delivery of various herbal drugs. Many herbal compounds including quercetin, genistein, naringin, sinomenine, piperine, glycyrrhizin and nitrile glycoside have demonstrated capability to enhance the bioavailability. The objective of this review is to summarize various available novel drug delivery technologies which have been developed for delivery of drugs (herbal), and to achieve better therapeutic response. An attempt has also been made to compile a profile on bioavailability enhancers of herbal origin with the mechanism of action (wherever reported) and studies on improvement in drug bioavailability, exhibited particularly by natural compounds.

Bioavailability enhancers of herbal origin: an overview

Recently, the use of herbal medicines has been increased all over the world due to their therapeutic effects and fewer adverse effects as compared to the modern medicines. However, many herbal drugs and herbal extracts despite of their impressive in-vitro findings demonstrates less or negligible in-vivo activity due to their poor lipid solubility or improper molecular size, resulting in poor absorption and hence poor bioavailability. Nowadays with the advancement in the technology, novel drug delivery systems open the door towards the development of enhancing bioavailability of herbal drug delivery systems. For last one decade many novel carriers such as liposomes, microspheres, nanoparticles, transferosomes, ethosomes, lipid based systems etc. have been reported for successful modified delivery of various herbal drugs. Many herbal compounds including quercetin, genistein, naringin, sinomenine, piperine, glycyrrhizin and nitrile glycoside have demonstrated capability to enhance the bioavailability. The objective of this review is to summarize various available novel drug delivery technologies which have been developed for delivery of drugs (herbal), and to achieve better therapeutic response. An attempt has also been made to compile a profile on bioavailability enhancers of herbal origin with the mechanism of action (wherever reported) and studies on improvement in drug bioavailability, exhibited particularly by natural compounds.

Isolation and characterization of novel mucoadhesive biomaterial from Phoenix dactylifera.

Phoenix dactylifera belongs to the family Arecaceae. The current aim of our research work is to isolate bio-material from the fruit pulp of Phoenix dactylifera and evaluate its mucoadhesivity. The bio- material was isolated by simple economical process. The isolated biomaterial was subjected for determination of solubility, colour changing point, viscosity, surface tension, pH and chemical tests. The mucoadhesivity of the biomaterial was assessed by shear stress method and rotating cylinder method using Capra aegagrus labium and intestine as mucosal substrates. The results were compared with HPMC and sodium CMC. The research study revealed that the biomaterial from Phoenix dactylifera exhibits promising inbuilt mucoadhesivity. So it can serve as a powerful natural mucoadhesant and may be used to develop mucoadhesive transmucosal drug delivery systems.

Isolation and characterization of novel mucoadhesive biomaterial from Phoenix dactylifera.

Phoenix dactylifera belongs to the family Arecaceae. The current aim of our research work is to isolate bio-material from the fruit pulp of Phoenix dactylifera and evaluate its mucoadhesivity. The bio- material was isolated by simple economical process. The isolated biomaterial was subjected for determination of solubility, colour changing point, viscosity, surface tension, pH and chemical tests. The mucoadhesivity of the biomaterial was assessed by shear stress method and rotating cylinder method using Capra aegagrus labium and intestine as mucosal substrates. The results were compared with HPMC and sodium CMC. The research study revealed that the biomaterial from Phoenix dactylifera exhibits promising inbuilt mucoadhesivity. So it can serve as a powerful natural mucoadhesant and may be used to develop mucoadhesive transmucosal drug delivery systems.

Novel Mucoadhesive Polymers –A Review.

The current article focuses on polymers used in mucosal delivery of therapeutic agents. The mucoadhesive drug delivery system is a popular novel drug delivery method because mucous membranes are relatively permeable, allowing for the rapid uptake of a drug into the systemic circulation and avoiding the first pass metabolism. Mucoadhesive polymers have been utilized in many different dosage forms in efforts to achieve systemic delivery of drugs through the different mucosa. These dosage forms include tablets, patches, tapes, films, semisolids and powders. The objective of this review is to study about novel mucoadhesive polymers and to design improved drug delivery systems.

Mouth dissolving tablets- a novel drug delivery system.

The past decade has thrown open the doors for continuous technological advancements in the pharmaceutical sector. Mouth Dissolving Tablets are one of the fruitful results of these technological advancements. MD tablets play a major role in improving the patient’s compliance. They rapidly disintegrate in the saliva hence obviating the need of the water. With the increasing incidences of non-compliance among the patients, Mouth dissolving tablets are the perfect answer to all these problems. A variety of drugs can be administered in the form of MD tablets as they give the advantage of the liquid medication in the solid preparation. These novel types of dosage forms have found acceptance among the geriatric, pediatric and dysphagic patients.

Topical treatment in vitiligo and the potential uses of new drug delivery systems.

Vitiligo is a psychologically devastating condition. Topical therapy is employed as first-line treatment in localized vitiligo. Currently, several topical agents are available in many forms viz. methoxsalen (solution and cream), trioxsalen (solution), corticosteroids (gel, cream, ointment and solution) and calcineurin inhibitors (ointment and cream). Although topical therapy has an important position in vitiligo treatment, side-effects or poor efficacy affect their utility and patient compliance. Novel drug delivery strategies can play a pivotal role in improving the topical delivery of various drugs by enhancing their epidermal localization with a concomitant reduction in their side-effects and improving their effectiveness. The current review emphasizes the potential of various phospholipid based carriers viz. liposomes, transferosomes, ethosomes, lipid emulsions, solid lipid nanoparticles and organogels in optimizing and enhancing the topical delivery of anti-vitiligo agents, whilst reducing the side effects of drugs commonly used in its topical treatment.