Bioadhesive Microparticles and Liposomes of Anti-Parkinson Drugs for Nasal Delivery

The nasal route is highly promising for the delivery of drugs exerting local effects in the nose or for therapeutic molecules having systemic or CNS effect. This is attributed to the fact that the nasal epithelium is highly vascularized and permeable, which ensures rapid absorption of the drug. The limitation of short residence time of the formulations in the nose and poor bioavailability of hydrophilic drugs could be overcome by the inclusion of bioadhesive agents into formulation. The main objective of this study was to develop novel bioadhesive microspheres and liposomes entrapping the anti-Parkinson drugs ropinirole hydrochloride (RH). The microspheres were prepared via spray drying in combination with chitosan or sodium alginate and the liposomes were prepared using the ethanol-based proliposome method. This study has investigated the potential of powdered mucoadhesive microparticles and liquid liposomes for nasal delivery via Miat® nasal insufflator and nasal spray devices respectively. Optimum mucoadhesive chitosan microparticles were prepared by co-spray drying of chitosan glutamate and ropinirole hydrochloride (90:10 w/w). Characterization studies have revealed that the drug following spray drying was amorphous and the microparticles were spherical and offered drug entrapment efficiency values in the range of 93 - 99%. The optimum formulation provided maximum swelling capacity and slowest drug release. Ex vivo toxicity study using isolated sheep nasal mucosa proved the safety of the optimized formulations for intranasal delivery. Investigation of powder delivery demonstrated that the Miat® nasal insufflator could deliver 90% of the dose with the first puff regardless of the loading weight used to fill the capsule fitted into the nasal device. The spray cloud had elongated shape and was homogenous; this is expected to enhance the impaction of the formulation in the nose following delivery from the nasal device. The properties of sodium alginate microparticles prepared via spray drying were highly dependent on inlet temperature of the spray drier, affecting particle morphology and product yield percent. The best performing particles were obtained when the inlet temperature was 140oC. Alginate to RH ratio had marked effect on particle size (2.60 - 4.37µm), entrapment efficiency (101 – 109%), physical state of the encapsulated RH, and morphology and surface smoothness of the particles as shown by scanning electron microscopy (SEM). In vitro drug release profile showed the amount of sodium alginate in formulations has controlled the rate of drug release. Results revealed that RH-alginate microparticles in 90:10 w/w polymer to drug ratio was the best performing spray dried formulation. Toxicity study proved safety of RH loaded sodium alginate for intranasal delivery. In contrast to RH-chitosan microparticles, particle trajectories was found from the cloud generated from emitted powder and laser diffraction demonstrated that powder was less likely to deposit in the lower respiratory tract owing to particle agglomeration. Ethanol-based proliposome technology produced oligolamellar liposomes from lipid ethanolic solutions as revealed by transmission electron microscopy (TEM). The resultant liposomes entrapped approximately 23.30% of the drug. Using five different bioadhesive agents, inclusion of any of these agents (0.2% w/v) caused a decrease in drug entrapment except for carboxymethyl chitosan which had no effect on the drug entrapment (25.97%). Investigation of aerosolized liposome dispersion using a range of nasal spray devices demonstrated integrity of liposomes were not changed (i.e particle size, Span, and drug entrapment efficiency were unaffected) and RH-loaded liposomes were efficiently delivered from the devices. In conclusion, the finding of this study explored mucoadhesive microspheres entrapped the anti-Parkinson drug, RH, and can potentially be applicable for nasal delivery to enhance nose to brain transport using nasal insufflator for improvement of the symptoms of Parkinson disease and Restless legs syndrome. Similar findings using nasal sprays were found for liposomes. In vivo studies are required in the future to determine the amount of the drug that may reach the blood circulation and brain

Spray-Dried Alginate Microparticles for Potential Intranasal Delivery of Ropinirole Hydrochloride: Development, Characterization and Histopathological Evaluation

Ropinirole hydrochloride (RH) is an anti-Parkinson drug with relativity low oral bioavailability owing to its extensive hepatic first pass metabolism. Spray-dried mucoadhesive alginate microspheres of RH were developed and characterized followed by histopathological evaluation using nasal tissue isolated from sheep. Spherical microparticles having high product yield (around 70%) were obtained when the inlet temperature of spray drying was 140 °C. Fourier Transform Infrared (FTIR) studies revealed the compatibility of the drug with the polymer, and scanning electron microscopy (SEM) showed that drug-loaded microparticles were spherical, and the apparent surface roughness was inversely related to the ratio of polymer to drug. Furthermore, size of the spray-dried particles were in the range of 2.5 - 4.37 µm, depending on formulation. All formulations had high drug encapsulation efficiencies (101 - 106%). Drug loaded into the polymeric particles was in the amorphous state and drug molecules were molecularly dispersed in the polymeric matrix of the microparticles which were revealed by X-ray diffraction and differential scanning calorimetry (DSC), respectively. The in vitro drug release was influenced by polymer concentration. Histopathological study demonstrated that RH-loaded sodium alginate microparticles was safe to nasal epithelium. In conclusion, spray drying of RH using sodium alginate polymer has produced microparticles of suitable characteristics for potential intranasal administration

Spray-Dried Proliposome Microparticles for High-Performance Aerosol Delivery Using a Monodose Powder Inhaler

Proliposome formulations containing salbutamol sulphate (SS) were developed using spray drying, and the effects of carrier type (lactose monohydrate (LMH) or mannitol) and lipid to carrier ratio were evaluated. The lipid phase comprised soy phosphatidylcholine (SPC) and cholesterol (1:1), and the ratios of lipid to carrier were 1:2, 1:4, 1:6, 1:8 or 1:10 w/w. X-ray powder diffraction (XRPD) revealed an interaction between the components of the proliposome particles, and scanning electron microscopy (SEM) showed that mannitol-based proliposomes were uniformly sized and spherical, whilst LMH-based proliposomes were irregular and relatively large. Using a two-stage impinger (TSI), fine particle fraction (FPF) values of the proliposomes were higher for mannitol-based formulations, reaching 52.6%, which was attributed to the better flow properties when mannitol was used as carrier. Following hydration of proliposomes, transmission electron microscopy (TEM) demonstrated that vesicles generated from mannitol-based formulations were oligolamellar, whilst LMH-based proliposomes generated 'worm-like' structures and vesicle clusters. Vesicle size decreased upon increasing carrier to lipid ratio, and the zeta potential values were negative. Drug entrapment efficiency (EE) was higher for liposomes generated from LMH-based proliposomes, reaching 37.76% when 1:2 lipid to carrier ratio was used. The in vitro drug release profile was similar for both carriers when 1:6 lipid to carrier ratio was used. This study showed that spray drying can produce inhalable proliposome microparticles that can generate liposomes upon contact with an aqueous phase, and the FPF of proliposomes and the EE offered by liposomes were formulation-dependent

Electronic bandgap miniaturized UWB antenna for near-field microwave investigation of skin

Near-field microwave investigation and tomography has many practical applications, especially where the trend of fields and signals in different environments is vital. This article shows an elliptical patch ultra-wideband antenna fed by a transmission line for the near-field characterization of cancerous cells in the skin. The antenna comprises an elliptical patch, stub loading to shift the band to lower bands, and an electronic bandgap structure on the ground side. Even though the antenna has a low profile of 15 × 15 mm2, the proposed antenna has more promising results than recent studies. Furthermore, both simulated near-field and far-field results show a broad bandwidth of 3.9–30 GHz and a resonance at 2.4 GHz applicable for industrial, scientific, and medical band applications. The proposed antenna also illustrates a peak gain of 6.48 dBi and a peak directivity of 7.09 dBi. Free space and skin (on a layer of breast fat and a tumor with a diameter of 4 mm at the boundary of skin and breast) are used as test environments during the simulation and measurement of near-field and far-field investigations while considering a phantom breast shape. Both far-field and near-field microwave investigations are performed in Computer Simulation Technology studio, and results are then compared with the measured data. The simulated and measured results are in good agreement, and the focused energy around the tumor is completely reconstructed. Therefore, the proposed antenna can be an adequate candidate for the differentiation of breast skin and tumor to reconstruct the tumor’s image

Advances in nasal drug delivery systems

Nasal drug delivery has been around for centuries and employed both leisure and recreations and also for the treatment of various conditions such as migraine, decongestion, sinusitis, rhinitis, and in emergency. The route is convenient and popular. It has numerous advantages such as direct delivery to the (central nervous system) CNS, high bioavailability, large surface area, needles are not used, and no special skills are required to deliver the drug. The method is non-invasive and provides direct drug transfer from nose to brain via olfactory nerve, hence it bypasses the blood-brain barrier for CNS effect and first pass effect while drug absorbed via nasal mucosa for systemic effect. It is also suitable for drugs that are unstable in an acid environment. The two main mechanisms in nasal drug delivery are discussed along with various factors involved such as physicochemical properties of the drug, formulations factors, and the physiological and anatomical characteristics. Various barriers effecting nasal drug delivery are also discussed. The delivery of microspheres and liposome formations using various nasal devices is also discussed

Bayesian machine learning analysis with Markov Chain Monte Carlo techniques for assessing characteristics and risk factors of Covid-19 in Erbil City-Iraq 2020–2021

The study aims to showcase machine learning techniques in the application of medical datasets for improving identification of correlations and relationships between variables, which will lead to more informed decision-making. Unlike other studies, intensive statistical modelling is used to understand and find the effective of variables cause to lead death due to Covid-19. Due to large dataset, not common approaches derive us to ideal conclusion. Furthermore, Bayesian technique is applied to generate predictive posterior distributions of the unknown parameters in the model in neural network as well as logistic regression, which helps us to avoid overfitting in machine learning applications and have additional measurements in assessing fitted model performance. According to the results extracted from the statistical analysis, the Bayesian neural network demonstrated superior performance in terms of classification measurements such as AUC (84.66%), F1 (87.11%), Precision (88.29%), and Recall (85.96%). The Bayesian logistic regression also performed well, but with slightly lower scores, achieving AUC (83.07%), F1 (85.59%), Precision (84.55%), and Recall (85.59%). In contrast, logistic regression (MLE) technique had the worst performance with very low scores (AUC = 52.38%, F1 = 57.55%, Precision = 57.01%, Recall = 58.10%). Regarding the variables' association with mortality, stepwise forward selection helped to identify seven significant variables. Age was found to be the most significant variable in predicting the probability of dying, with patients in the age group of (18–44) having 12 times higher odds, patients in the age group of (45–64) having 123 more odds, and patients above 65 years old having 436 times more chance to die compared to patients below 18 years old. Severe coughing was also significant with 7.26 odds, and patients suffering from diabetes had 2.82 times more chance to die. Moreover, SpO2 contributed to a decrease of 20% in the relative risk of dying from Covid-19 disease. Gender and Smoking did not show a significant association with mortality. Finally, the Bayesian approach showed higher sensitivity and specificity than the classic neural network