Pharmaceutical Nanotechnology - Volume 8, Issue 3, 2020

Coordinative interactions between multivalent metal ions and drug derivatives with Lewis base functions give rise to nanoscale coordination polymers (NCPs) as delivery systems. As the pharmacologically active agent constitutes a main building block of the nanomaterial, the resulting drug loadings are typically very high. By additionally selecting metal ions with favorable pharmacological or physicochemical properties, the obtained NCPs are predominantly composed of active components which serve individual purposes, such as pharmacotherapy, photosensitization, multimodal imaging, chemodynamic therapy or radiosensitization. By this approach, the assembly of drug molecules into NCPs modulates pharmacokinetics, combines pharmacological drug action with specific characteristics of metal components and provides a strategy to generate tailorable multifunctional nanoparticles. This article reviews different applications and recent examples of such highly functional nanopharmaceuticals with a high ‘material economy’. Lay Summary: Nanoparticles, that are small enough to circulate in the bloodstream and can carry cargo molecules, such as drugs, imaging or contrast agents, are attractive materials for pharmaceutical applications. A high loading capacity is a generally aspired parameter of nanopharmaceuticals to minimize patient exposure to unnecessary nanomaterial. Pharmaceutical agents containing Lewis base functions in their molecular structure can directly be assembled into metal-organic nanopharmaceuticals by coordinative interaction with metal ions. Such coordination polymers generally feature extraordinarily high loading capacities and the flexibility to encapsulate different agents for a simultaneous delivery in combination therapy or ‘theranostic’ applications.

Background: Nanofibers are used in topical medication for various skin diseases like wound healing, skin cancer and others. Non-melanoma skin cancers (NMSCs) are the most widely distributed diseases in the world, of which 99% of people are affected by either basal cell carcinomas (BCCs) or squamous cell carcinomas (SCCs) of the skin. Skin malignancy is caused by direct sun exposure and regular application of unsafe restorative items on the skin. Objective: This review presents the use of nanofibers in skin cancer treatment and advances made in skin cancer treatment. Methods: There are various methods used in the production of nanofibers such as bicomponent extrusion, phase separation, template synthesis, drawing, electrospinning, and others. Electrospinning is the most widely used technique for nanofiber fabrication. The nanofibers are produced in nanometer size range and mostly used in medication because of their low thickness, large surface area per unit mass and porosity. Nanofibers are also used as drug delivery system for sustaining the action of drugs or medicaments. Results: Nanofibers enhance the permeation and availability of those drugs having low bioavailability and low permeability. Nanofibers increase the sustainability of the drugs up to 10 days. Conclusion: Skin cancer is the abnormal growth of skin cells in the body influencing people of all colours and skin. In this review paper, the definition and production techniques of nanofibers and drugs used in skin cancer treatment and the relation between skin cancer and nanofiber are illustrated in detail. With the help of different techniques and drugs, the risk of non-melanoma skin cancer is reduced. Lay Summary: The risk of skin cancer and other skin problems is increasing day by day. In a previous study we found that the nanofibers are less used as a topical delivery system. We have studied the nanofibers as a drug delivery system in the treatment of skin cancer by using different drugs. According our study nanofibers are most useful in skin drug delivery and if the nanofiber, are merging with other drug delivery system like nanoparticles, it may maximize the output of drug into skin. The significance of this study is, to explain all information about nanofibers in skin cancer.

Background: Carvedilol (CD), a non-selective beta-blocker, is indicated for the management of mild to moderate congestive heart failure. After oral administration, CD is rapidly absorbed with an absolute bioavailability of 18-25% because of low solubility and extensive first-pass metabolism. Objective: The present investigation focused on enhanced oral delivery of CD using supersaturated self-emulsifying drug delivery (SEDDS) system. Methods: Optimized SEDDS consisted of a blend of Oleic acid and Labrafil-M2125 as an oil-phase, Cremophor-RH40, polyethylene glycol-400 and HPMC-E5 as a surfactant, co-surfactant and supersaturation promoter respectively. Formulations were characterized for physical characteristics, invitro release in simulated and biorelevant dissolution media, intestinal permeability and bioavailability studies in Wistar rats. Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) analysis, scanning electron microscopy (SEM) studies were used to confirm the crystalline nature and shape of the optimized formulation. Results: DSC and XRD, SEM studies showed that the drug was in amorphous form, and droplets were spherical in shape. Dissolution studies clearly showed distinct CD release in compendial and biorelevant dissolution media. The results from permeability and in-vivo studies depicted 2.2-folds and 3.2-folds increase in permeability and bioavailability, respectively from supersaturated SEDDS in comparison with control. Conclusion: The results conclusively confirmed that the SEDDS formulation could be considered as a new alternative delivery vehicle for the oral supply of CD. Lay Summary: Carvedilol (CD) is a non-selective antihypertensive drug with poor oral bioavailability. Previously, various lipid delivery systems were reported with enhanced oral delivery. We developed suprsaturable SEDDS formulation with immediate onset of action. SEDDS formulation was developed and optimized as per the established protocols. The optimized SEDDS formulation was stable over three months and converted to solid and supersaturated SEDDS. The results from permeability and in-vivo studies demonstrated an enhancement in permeability and bioavailability from supersaturated SEDDS in comparison with control. The results conclusively confirmed that the SEDDS formulation could be considered as a new alternative delivery vehicle for the oral administration of CD.

Background: Excessive use of diazinon, as an organophosphate pesticide (OP), contributes to cytotoxic and pathologic cellular damage and, in particular, oxidative stress. However, metal-oxide nanoparticles (NPs), such as cerium oxide (CeO2) and yttrium oxide (Y2O3), with the property of free radical scavenging demonstrated beneficial effects in the alleviation of oxidative stress biomarkers. Objective: The aims of this study include evaluating beneficial effects of CeO2 NPs, Y2O3 NPs, and their combination against diazinon-induced oxidative stress in different tissues of brain, heart, lung, kidney, liver, and spleen. Methods: Eight randomized groups of 6 adult male Wistar rats were formed. Each group of rats administered a different combination of diazinon, CeO2 and Y2O3 NPs daily and levels of oxidative stress markers, such as reactive oxygen species (ROS), lipid peroxidation (LPO), total thiol molecules (TTM) and total anti-oxidant power (TAP) and catalase enzyme, were measured after 2 weeks of the treatment. Results: Measurements of the mentioned markers in the brain, heart, lung, kidney, liver, and spleen showed that the administration of NPs could significantly alleviate the oxidative stress induced by diazinon. However, the findings of this study illustrated that the combination of both CeO2 and Y2O3 NPs led to a better reduction in oxidative stress markers. Conclusion: Sub-acute exposure of diazinon in rats led to increased levels of oxidative stress markers in pivotal tissues such as the brain, heart, lung, kidney, liver, and spleen. CeO2 and Y2O3 NPs neutralize the oxidative stress to compensate diazinon-induced tissue damages. Lay Summary: Organophosphate pesticides (OPs), which are mainly used for pest control, are responsible for the entry of pesticides into the human food cycle. Organophosphate such as diazinon increases the molecular biomarkers of oxidative stress inside the cells of vital tissues such as the heart, liver, lungs, etc. Metal oxide nanoparticles (NPs) such as cerium oxide (CeO2) and yitrium oxide (Y2O3) can have free radical scavenging potential under oxidative stress and through various mechanisms. Although these nanoparticles reduce oxidative stress, it should be borne in the design of the study that additional doses of these substances reverse the beneficial effects.

Background: Insulin, like most peptides, is classified as a hydrophilic and macromolecular drug that is considered as a low permeable and unstable compound in the gastrointestinal (GI) tract. The acidic condition of the stomach can degrade insulin molecules. Moreover, the presence of proteolytic activities of some enzymes such as trypsin and chymotrypsin can hydrolyze amide-bonds between various amino-acids in the structures of peptides and proteins. However, due to its simplicity and high patient compliance, oral administration is the most preferred route of systemic drug delivery, and for the development of an oral delivery system, some obstacles in oral administration of peptides and proteins including low permeability and low stability of the proteins in GI should be overcome. Objective: In this study, the effects of orally insulin nanoparticles (INPs) prepared from quaternerized N-aryl derivatives of chitosan on the biochemical factors of the liver in diabetic rats were studied. Methods: INPs composed of methylated (amino benzyl) chitosan were prepared by the PEC method. Lyophilized INPs were filled in pre-clinical capsules, and the capsules were enteric-coated with Eudragit L100. Twenty Male Wistar rats were randomly divided into four groups: group1: normal control rats, group 2: diabetic rats, group 3: diabetic rats received capsules INPs(30 U/kg/day, orally), group 4: the diabetic rats received regular insulin (5 U/kg/day, subcutaneously). At the end of the treatment, serum, liver and kidney tissues were collected. Biochemical parameters in serum were measured using spectrophotometric methods. Also, oxidative stress was measured in plasma, liver and kidney. Histological studies were performed using H and E staining . Results: Biochemical parameters, and liver and kidney injury markers in serum of the diabetic rats that received INPs improved significantly compared with the diabetic group. INPs reduced oxidative toxic stress biomarkers in serum, liver and kidney of the diabetic treated group. Furthermore, a histopathological change was developed in the treated groups. Conclusion: Capsulated INPs can prevent diabetic liver and oxidative kidney damages (similar regular insulin). Therefore oral administration of INPs appears to be safe. Lay Summary: Although oral route is the most preferred route of administration, but oral delivery of peptides and proteins is still a challenging issue. Diabetes Mellitus may lead to severe complications, which most of them are life-threatening. In this study, we are testing the toxicity of oral insulin nanoparticles in kidney and liver of rats. For this investigation, we will prepare insulin nanoparticles composed of a quaternized derivative of chitosan. The nanoparticles will be administered orally to rats and the level of oxidative stress in their liver and kidney will be determined. The data will be compared to the subcutaneous injection of insulin.