Andrographolide Loaded in Micro-and Nano-Formulations: Improved Bioavailability, Target-Tissue Distribution, and Efficacy of the “King of Bitters”

Andrographolide (AG) is the characteristic constituent of Andrographis paniculata, of the Acanthaceae family. This plant is a well-known Asian medicinal plant that is widely used in India, China, and Thailand. A monograph of Herba Andrographidis (Chuanxinlian) is included in the Chinese Pharmacopoeia, which reports that this decoction can “remove heat, counteract toxicity, and reduce swellings.” The numerous potential activities of AG range from anti-inflammatory to anti-diabetic action, from neuroprotection to antitumor activity, and from hepatoprotective to anti-obesity properties. However, AG has low bioavailability and poor water solubility, which can limit its distribution and accumulation in the body after administration. In addition, AG is not stable in gastrointestinal alkaline and acidic environments, and has been reported to have a very short half-life. Among the diverse strategies that have been adopted to increase AG water solubility and permeability, the technological approach is the most useful way to develop appropriate delivery systems. This review reports on published studies related to microparticles (MPs) and nanoparticles (NPs) loaded with AG. MPs based on polylactic-glycolic acid (PLGA), alginic acid, and glucan derivatives have been developed for parenteral oral and pulmonary administration, respectively. NPs include vesicles (both liposomes and niosomes);polymeric NPs (based on polyvinyl alcohol, polymerized phenylboronic acid, PLGA, human serum albumin, poly ethylcyanoacrylate, and polymeric micelles);solid lipid NPs;microemulsions and nanoemulsions;gold NPs;nanocrystals;and nanosuspensions. Improved bioavailability, target-tissue distribution, and efficacy of AG loaded in the described drug delivery systems have been reported.

Flavonoids Loaded in Nanocarriers: An Opportunity to Increase Oral Bioavailability and Bioefficacy

Flavonoids are among the biggest group of polyphenols, widely distributed in plant-based foods. A plethora of evidence supports the health benefits and value of flavonoids can play in the physiological function treatment and in the prevention of disease particularly in the prevention of degenerative conditions including cancers, cardiovascular and neurodegenerative diseases. Hence, flavonoids represent the active constituents of many dietary supplements and herbal remedies, as well as there is an increasing interest in this class of polyphenols as functional ingredients of beverages, food grains and dairy products. Conversely, various studies have also shown that flavonoids have some drawbacks after oral administration such as stability, bioavailability and bioefficacy. This article reviews the current status of novel nanodelivery systems including nanospheres, nanocaspsules, micro- and nanoemulsions, micelles, solid lipid nanoparticles and nanostructured lipid capsules, successfully developed for overcoming the delivery challenges of flavonoids.

Nanocarriers to Enhance Solubility, Bioavailability, and Efficacy of Artemisinins

The therapeutic potential of artemisinin (ART) and its derivatives (ARTs) is not limited to malaria but has been recently expanded to other infections with protozoans, trematodes, or viruses as well as to cancer. Due to their limited poor water and oil solubility, rapid degradation by the liver, and short half-life, they have a low bioavailability after oral administration. Consequently, there is a pressing necessity to formulate new ART preparations to raise its bioavailability and efficacy. Nanosized drug delivery systems represent important tools in modern medicine with wide clinical applications, because of their potential modulation of pharmacokinetic and biodistribution. This review focuses on polymer-based systems, lipid-based systems, and inorganic nanoparticles loaded with ARTs. The overall goal of this field of research is to enhance their solubility and stability to improve bioavailability at much lower doses and to increase long-term safety. In addition, the opportunity to reach highly specific site-targeted delivery by these nanocarriers confers a high medicinal value. Remarkably, most of the reported nanoparticulate drug delivery systems are biologically inactive or marginally immunogenic, generating no antigenic or pyrogenic reactions but only partial intrinsic toxicity. As clinical studies in human patients are available so far, there is a pressing need to translate preclinical results on ART-based nanosystems into clinical settings.

Expanding the Therapeutic Spectrum of Artemisinin:Activity Against Infectious Diseases Beyond Malaria and Novel Pharmaceutical Developments

The interest of Western medicine in Traditional Chinese Medicine(TCM) as a source of drug leads/new drugs to treat diseases without available efficient therapies has been dramatically augmented in the last decades by the extensive work and the outstanding findings achieved within this kind of medicine. The practice of TCM over thousands of years has equipped scientists with substantial experience with hundreds of plants that led to the discovery of artemisinin(qinghaosu), which is extracted from the medicinal plant Artemisia annua L.(qinghao). The unexpected success of artemisinin in combating malaria has drawn strong attention from the scientific community towards TCM. Artemisinin was discovered by Youyou Tu in 1972. Since then, several novel pharmacological activities based on the well-known properties of the sesquiterpene lactone structure with the oxepane ring and an endoperoxide bridge have been unravelled. Beyond malaria, artemisinin and its derivatives(artemisinins) exert profound activities towards other protozoans(Leishmania, Trypanosoma, amoebas, Neospora caninum, and Eimeria tenella), trematodes(Schistosoma, liver flukes), and viruses(human cytomegalovirus, hepatitis B and C viruses). Less clear is the effect against bacteria and fungi. Based on the promising results of artemisinin and the first generation derivatives(artesunate, artemether, arteether), novel drug development strategies have been pursued.These included the synthesis of acetal-and non-acetal-type artemisinin dimeric molecules as well as developing nanotechnological approaches, e.g.artemisinin-based liposomes, niosomes, micelles, solid lipid nanocarriers, nanostructured lipid carriers, nanoparticles, fullerenes and nanotubes. The current review presents an overview on different aspects of artemisinins, including sources, chemistry, biological/pharmacological properties, types of infectious pathogens that are susceptible to artemisinins in vitro and in vivo, in addition to the advancement in their drug delivery systems utilizing pharmaceutical technology. It would be expected that different therapeutic strategies based on the second and third generation artemisinin derivatives and artemisinin-based drug technologies would be available in the near future to treat specific infectious diseases.