Exploring Novel Strategies for Lipid-Based Drug Delivery

Currently, the concept of lipid-based drug delivery systems has gained much interest because of their capability to deliver drugs which dissolve sparingly in water or insoluble in nature. Several methods of lipid-based drug delivery exist, and each method has its own advantages as well as limitations. The primary objective of the formulation development is to improve the bioavailability of the drug. The nano-sized lipid-based drug delivery systems have enough potential to do so. This article addresses the various barriers to the transportation of drugs through certain routes and also the common excipients which used to develop the lipid-based drug delivery systems. It provides a thorough overview of the lipid formulation classification scheme (LFCS) and also deals with several formulation & evaluation aspects of lipid-based drug delivery system. Further, it focuses on the formulations which are already available in the market and their regulatory concerns, respectively.

Overview of Multicomponent Solid Forms

Multi-drug therapy involves the simultaneous or sequential administration of two or more drugs with similar or different mechanisms of action and is efficient in combating various ailments such as cancer, diabetes, and rheumatoid arthritis. It has emerged advantageous due to larger therapeutic benefits, an increase in patient compliance, lower administrative costs, and reduced number of prescriptions. In the recent past, the clinical success of the Novartis product Entresto (sacubitril, disodium valsartan and water) and Esteve product E-58425 (tramadol and celecoxib) has boosted the development of multi-drug . The present article is hence designed to provide an overview of different multicomponent addicts which provide option of combining the drugs at a supramolecular level (nano-sized level). Key features of multi-drug cocrystal, co-amorphous system and eutectics are described with major emphasis on screening tools, preparation methods, characterization techniques, biopharmaceutical aspects and scale up.

Interaction of Riboflavin-5-Phosphate With Liposome Bilayers

Riboflavin presents tremendous potential as a photosensitizing agent for photodynamic therapy (PDT) for treating microbial infection and cancer therapy. Encapsulation of riboflavin can improve its bioavailability and stability while making the clinical applications more efficient. The authors' detailed study on cellular inhibition of liposome encapsulated riboflavin-5-phosphate investigation, and the effect of unencapsulated riboflavin on liposome bilayers aims to improve the efficiency of cellular delivery of riboflavin. Nano-sized liposomes composed of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and cholesterol were used in this study. Cell studies demonstrate high inhibition rates for the lipsome-encapsualted high concentration riboflavin formulations in the presence of blue light, despite the lower encapsulation lading.

A Computational Study of the Combustion of Hydrazine with Dinitrogen Tetroxide

In this article, density functional theory (DFT) based on ab initio molecular dynamics (AIMD) is used to study the combustion reaction of a specific rocket fuel, hydrazine (N2H4), accomplished by using dinitrogen tetroxide (N2O4) as the oxidant. The atomic model consists of 1:1 ratio of N2H4 and N2O4 molecules. Nano droplets of fuel and oxidizer are injected into the combustion chamber which experience collision, mixture, and chemical interaction. The AIMD simulation of chemical reaction of fuel and oxidizer is performed under the initial conditions of high temperature and pressure. In the AIMD trajectory, one observes several energetically favorable products such as NO, NO2, and H2O. The mechanism for the formation of H2O and other toxic and non-toxic products are proposed based on simulation results.

Nanomaterials in Medical Devices: Regulations' Review and Future Perspectives

This article gives a brief description of the existing regulations related to biomaterials safety that need to be considered before it is introduced into EU market. According to these regulations, the risk analysis should include two characteristics: probability of occurrence of harm, and severity. Identified user-related harm should be reduced by managing the risk. Additionally, the review presents an overview of engineered biomaterials (EBMs), which in combination with nanoscale components (NPs) have shown promises in Advanced Therapy Medicinal Products (ATMP) and Medical Devices (MD). In this article, recent challenges, objectives and perspectives in risk assessment and risk management of ATMP and MD composed of nanobiomaterials were also highlighted.

Comparison of Freeze and Spray Drying to Obtain Primaquine-Loaded Solid Lipid Nanoparticles

This article describes how the spray drying and freeze drying of various nanosized Solid Lipid Nanoparticle (SLN) and the physicochemical attributes of the acquired particles were examined. Primaquine loaded Solid Lipid Nanoparticles dried by the two strategies is examined. Particles were characterised by determination of size, drug loading, encapsulation efficiency and surface morphology. In vitro and kinetic drug discharge models were also considered. Preparation parameters have no impact on the molecule morphology and properties, and the main parameter deciding the molecule attributes in the drug substance of the nanoparticle, either in the spraying or in the freezing technique of drying. The drug release profile of spray dried SLN is superior to that of the freeze dried SLN.

Development and Validation of a GC-MS Method for the Quantitation of Nanoformulated Primaquine in Whole Blood and Plasma of Mouse Model

A Gas chromatography-mass spectrometry (GC/MS) method was developed and validated for the quantitation of the antimalarial drug, nanoformulated Primaquine (PQ), in whole blood and plasma. The analyte was extracted using a protein precipitation method followed by chromatographic separation on a Waters Xterra, RP C8, 2.5µm, 50mm x 4.6mm analytical column with a mobile phase consisting of A: 0.5% Formic acid in 20mM NH4COOH, B: Methanol pH adjusted to 3.0 with FA at a ratio of 3:7 (v/v), delivered at a constant flow rate of 0.5 ml/min. Mefloquine (MEF) was used as the internal standard. Compound reaction monitoring was performed using 260.4 Da for precursor ion and 175. 2 and 379.2 Da for product ions for the quantification of PQ and 379.2 Da for precursor ion and 175.2 and 379.2 Da for product ions for the quantification, respectively. Calibration curves were constructed over the concentration range 16.7–4300 ng/ml. The mean intra- and inter-assay accuracy values for the analysis of PQ in WB was 104% (%CV = 5.6) and 98.6% (%CV = 5.7), respectively. The mean intra- and inter-assay accuracy values for the analysis of PQ in plasma was 92.7% (%CV = 3.7) and 93.7% (%CV = 5.4), respectively. No significant matrix effect was observed during the method validation. The validated method was applied to an absorption study in mice, to determine and compare PQ concentrations in whole blood and plasma samples. Results of the statistical analysis using a linear mixed effects growth curve model concluded that there was no significant difference (p-value = 0.688) between WB and plasma PQ concentrations. This method utilizes a small sample volume of 20 µl, facilitating low blood collection volumes and a short chromatographic run time of 3 min which allows for high sample through put analysis.

Drug-Nanoparticle Composites

Polymeric nanoparticles represent attractive targets for the controlled delivery of therapeutic drugs. Drug-nanoparticle conjugates are convenient targets to enhance solubility and membrane permeability of drugs, prolong circulation time and minimize non-specific uptake. The behavior of drugs-loaded nanoparticles is governed by various factors. Understanding of these effects is very important for design of drug-nanoparticle systems, that could be suitable for treating the particular diseases. The aim of the current study is a complementary molecular docking followed by quantitative structure-activity relationships modeling for drugs payload on polymeric nanoparticles. Twenty-one approved drugs were considered. Docking of drugs was performed towards a simplified polymeric surface. Binding energies agreed well with the observed mass loading. Quantitative structure-activity relationships model supported this data. Effects of electronegativity and hydrophobicity were discussed. Developed model may contribute to the development of other useful nano-sized polymeric drug carriers to deliver a spectrum of therapeutic and imaging agents for medical purposes.

Assessment of Crystal Morphology on Uptake, Particle Dissolution, and Toxicity of Nanoscale Titanium Dioxide on Artemia Salina

Knowledge of nanomaterial toxicity is critical to avoid adverse effects on human and environment health. In this study, the influences of crystal morphology on physico-chemical and toxic properties of nanoscale TiO2 (n- TiO2) were investigated. Artemia salina were exposed to anatase, rutile and mixture polymorphs of n-TiO2 in seawater. Short-term (24 h) and long-term (96 h) exposures were conducted in 1, 10 and 100 mg/L suspensions of n-TiO2 in the presence and absence of food. Anatase form had highest accumulation followed by mixture and rutile. Presence of food greatly reduced accumulation. n-TiO2 dissolution was not significant in seawater (p<0.05) nor was influenced from crystal structure. Highest toxic effects occurred in 96h exposure in the order of anatase>mixture>rutile. Mortality and oxidative stress levels increased with increasing n-TiO2 concentration and exposure time (p<0.05). Presence of food in the exposure medium alleviated the oxidative stress, indicating deprivation from food could promote toxic effects of n-TiO2 under long-term exposure.

Exploring Simple, Interpretable, and Predictive QSPR Model of Fullerene C60 Solubility in Organic Solvents

Buckminsterfullerene (C60) and its derivatives have currently been used as promising nanomaterial for diagnostic and therapeutic agents. They are applied in pharmaceutical industry due to their nanostructure characteristics, stability and hydrophobic character. Due to its sparingly soluble nature, the solubility of C60 has been of enormous attention among carbon nanostructure investigators owing to its fundamental importance and practical interest in nanotechnology and medical industry. In order to study the diverse role of C60 and its derivatives the dependence of fullerene's solubility on molecular structure of the solvent must be understood. Current study was dedicated to the exploration of the solubility of fullerene C60 in 156 organic solvents using simple, interpretable and predictive 1D and 2D descriptors employing quantitative structure-property relationship (QSPR) technique. The authors employed genetic algorithm followed by multiple linear regression analysis (GA-MLR) to generate the correlation models. The best performance is accomplished by the four-variable MLR model with internal and external prediction coefficient of Q2 = 0.86 and R2pred = 0.89. The study identified vital properties and structural fragments, particularly valuable for guiding future synthetic as well as prediction efforts. The model generated with the highest number of organic solvents to date with simple descriptors can be reproduced in no time to predict the solubility of C60 in any new or existing organic solvents. This approach can be used as an efficient predictor for fullerenes' solubility in various organic solvents.