Pharmaceutical Nanotechnology - Volume 8, Issue 4, 2020

Dry eye disease (DED) is a common multifactorial disease linked to the tears/ocular surface leading to eye discomfort, ocular surface damage, and visual disturbance. Antiinflammatory agents (steroids and cyclosporine A), hormonal therapy, antibiotics, nerve growth factors, essential fatty acids are used as treatment options of DED. Current therapies attempt to reduce the ocular discomfort by producing lubrication and stimulating gland/nerve(s) associated with tear production, without providing a permanent cure for dry eye. Nanocarrier systems show a great promise to revolutionize drug delivery in DED, offering many advantages such as site specific and sustained delivery of therapeutic agents. This review presents an overview, pathophysiology, prevalence and etiology of DED, with an emphasis on preclinical and clinical studies involving the use of nanocarrier systems in treating DED. Lay Summary: Dry eye disease (DED) is a multifactorial disease associated with tear deficiency or excessive tear evaporation. There are several review articles that summarize DED, disease symptoms, causes and treatment approaches. Nanocarrier systems show a great promise to revolutionize drug delivery in DED, offering many advantages such as site specific and sustained delivery of therapeutic agents. Very few review articles summarize the findings on the use of nanotherapeutics in DED. In this review, we have exclusively discussed the preclinical and clinical studies of nanotherapeutics in DED therapy. This information will be attractive to both academic and pharmaceutical industry researchers working in DED therapeutics.

Self-emulsifying drug delivery system (SEDDS) is a kind of solid or liquid formulation composed of drugs, oil, surfactant and cosurfactant. It could form a fine emulsion (micro/nano) in the gastrointestinal tract after oral administration. Later on, the formed emulsion is absorbed through the lymphatic pathway. The oral bioavailability of drugs in SEDDS would be improved for bypassing the first-pass effect of the liver. Therefore, SEDDS has become a vital strategy to increase the oral bioavailability of poor watersoluble drugs. In addition, there is no aqueous phase in SEDDS, thus SEDDS is a homogeneous system, consequently being suitable for large-scale production and more stable than conventional emulsion. However, the role of formulation aspects in the biological property of SEDDS is not fully clear. In order to prepare the satisfying SEDDS to improve oral drug bioavailability, we need to fully understand the various factors that affect the in vivo behavior of SEDDS. In this review, we would explore the role of ingredient (drugs, oils, surfactant and cosurfactant) of SEDDS in increasing oral drug bioavailability. We would also discuss the effect of physicochemical property (particle size and zeta potential) of SEDDS on the oral drug bioavailability enhancement. This review would provide an approach to develop a rational SEDDS to improving oral drug bioavailability. Lay Summary: Self-emulsifying drug-delivery system (SEDDS) has been proven to be promising in ameliorating the oral bioavailability of poor water-soluble drugs. This review highlighted the influence of excipients and physicochemical property of SEDDS on the formation of emulsion and the oral absorption of drugs in the body.

Background: Indomethacin (IND) is a class of non-steroidal, anti-inflammatory drugs, which is used to treat various kinds of ocular inflammation, and has been reported to prevent posterior capsule opacification (PCO) by inhibiting the mitosis and collagen synthesis of human lens epithelial cells (LECs). In addition, the specific absorption spectrum of indomethacin shows the effect of absorbing short-wavelength blue-violet light. Objective: We prepared an indomethacin-loaded hydrogel as a potential intraocular lens (IOLs) material to prevent endophthalmitis, PCO and filter harmful blue light. Methods: Indomethacin prodrugs (HEMA-IND) (HI) were prepared by esterification of indomethacin and 2-hydroxyethyl methacrylate (HEMA), and poly (HEMA-co-MAA-co-MMA-co- HI) (HAMI) hydrogels were prepared by free-radical polymerization of 2-hydroxyethyl methacrylate (HEMA), methyl methacrylate (MMA), methacrylic acid (MAA) and HI. The physical and chemical properties of obtained hydrogel were detected, including optical, morphology, thermomechanical and surface properties, equilibrium water content, drug release behaviors and cytotoxicity. Results: HAMI hydrogels can filter harmful short-wavelength blue light and show other necessary properties like visible light transparency, glass transition temperatures, mechanical strength, and biocompatibility for making intraocular lenses. Meanwhile, MAA increases the hydrophilicity of the hydrogels, resulting in a lower water contact angle and controllable drug release from the hydrogels. Conclusion: In summary, HAMI hydrogels show a great potential as IOL biomaterials that can maintain the sustained release of indomethacin and filter harmful blue light after cataract surgery. Lay Summary: People with cataract surgery can be at high risk of postoperative complications, such as PCO and postoperative endophthalmitis. Moreover, early IOLs allowed all ultraviolet (UV) and visible light to pass through retina without restriction, thus to damage the retina and the retinal pigment epithelium, which may lead to retinopathy and age-related macular degeneration (AMD). Herein, we sought to design and prepare a kind of IOLs loaded with indomethacin to mitigate those postoperative complications and filter harmful blue light to improve the treatment prognosis.

Background: Hypertension and hypercholesterolemia are two main physiological risk factors of cardiovascular disease, and commonly occur in combination. Multicompound combination therapy is rational for the treatment of concurrent hypertension and hypercholesterolemia, while telmisartan and pitavastatin calcium can be used as a potential drug combination. Objective: The aim of this paper is to study the intestinal absorption and absorption interaction of telmisartan and pitavastatin calcium. Methods: An HPLC method was developed and validated to determine telmisartan and pitavastatin calcium in intestinal perfusate simultaneously. The in situ single-pass perfusion in rats was utilized to investigate the effects of concentrations, intestinal segment (duodenum, jejunum, ileum and colon) and co-administrated drugs on absorption. Results: The effective permeability coefficient and the absorption rate constant of telmisartan were higher in the duodenum as compared to other intestinal segments. However, the intestinal absorption of pitavastatin calcium was not segmental dependent. The effective permeability coefficient and absorption rate constant have no significant difference among three concentrations of telmisartan, pitavastatin calcium individually and their combination. Conclusion: The results showed that telmisartan and pitavastatin calcium were transported passively, and telmisartan and pitavastatin calcium could be absorbed well in all intestinal segments. The intestinal absorption parameters revealed the absence of any intestinal absorption interaction when co-administered. Lay Summary: Co-administration of telmisartan and pitavastatin calcium can provide a potential therapeutic strategy for the treatment of concurrent hypertension and hypercholesterolemia. We are investigating the intestinal interaction of these two drugs in rats using the developed HPLC method and in situ single-pass perfusion technology. We will calculate some parameters after administrating two types of drugs either separately or together, which help reflect changes regarding intestinal absorption and penetration. Compared with telmisartan and pitavastatin calcium administrated separately, if parameters significantly change after co-administration, it proves the existence of the intestinal interactions. Moreover, the results might contribute to clinic drug monitoring.

Background: The newly emerged coronavirus SARS-CoV-2, first reported in December 2019, has infected about five and a half million people globally and resulted in nearly 9063264 deaths until the 24th of June 2020. Nevertheless, the highly contagious virus has instigated an unimaginably rapid response from scientific and medical communities. Objectives: Pioneering research on molecular mechanisms underlying the viral transmission, molecular pathogenicity, and potential treatments will be highlighted in this review. The development of antiviral drugs specific to SARS-CoV-2 is a complicated and tedious process. To accelerate scientific discoveries and advancement, researchers are consolidating available data from associated coronaviruses into a single pipeline, which can be readily made available to vaccine developers. Methods: In order to find studies evaluating the COVID-19 virus epidemiology, repurposed drugs and potential vaccines, web searches and bibliographical bases have been used with keywords that matches the content of this review. Results: The published results of SARS-CoV-2 structures and interactomics have been used to identify potential therapeutic candidates. We illustrate recent publications on SARS-CoV-2, concerning its molecular, epidemiological, and clinical characteristics, and focus on innovative diagnostics technologies in the production pipeline. This objective of this review is to enhance the comprehension of the unique characteristics of SARS-CoV-2 and strengthen future control measures. Lay Summary: An innovative analysis is evaluating the nature of the COVID-19 pandemic. The aim is to increase knowledge of possible viral detection methods, which highlights several new technology limitations and advantages. We have assessed some drugs currently for patients (Lopinavir, Ritonavir, Anakinra and Interferon beta 1a), as the feasibility of COVID-19 specific antivirals is not presently known. The study explores the race toward vaccine development and highlights some significant trials and candidates in various clinical phases. This research addresses critical knowledge gaps by identifying repurposed drugs currently under clinical trials. Findings will be fed back rapidly to the researchers interested in COVID 19 and support the evidence and potential of possible therapeutics and small molecules with their mode of action.