Chitosan-based buccal mucoadhesive patches to enhance the systemic bioavailability of tizanidine.

Tizanidine hydrochloride (TZN) is a muscle relaxant used to treat a variety of disorders such as painful muscle spasms and chronic spasticity. TZN has low oral bioavailability due to extensive first-pass metabolism and is used orally at a dose of 6-24 mg per day. In the present study, buccal patches were prepared by solvent casting method using chitosan glutamate (Chi-Glu) and novel chitosan azelate (Chi-Aze) which was synthesised in-house for the first time, to enhance the bioavailability of TZN by bypassing first-pass metabolism. The characterisation, mucoadhesion and drug release studies were performed. Chi-Aze patches retained their integrity longer in the buccal medium and showed higher ex vivo drug permeability compared to that prepared with Chi-Glu. In vivo studies revealed that buccal formulation fabricated with Chi-Aze (3%) showed approx 3 times more bioavailability than the orally administered commercial product. Results of the studies indicate that Chi-Aze, prepared by conjugation of chitosan and a fatty acid, the patch formulation is a promising buccal mucoadhesive system due to the physical stability in buccal medium, the good mucoadhesiveness and the high TZN bioavailability. Moreover, Chi-Aze patch might be an alternative to oral formulations of TZN to reduce the dose and frequency of drug administration.

New Era on Combining Both Imaging and Drug Delivery to Treat Cancer.

It is well documented that cancer is one of the leading causes of death worldwide. During the pandemic, cancer screening was suspended, and only symptomatic patients were referred for screening. It is believed that deaths related to various cancer types have increased by around 10%, and the screening suspension was assumed as the main reason. It is well documented that the early diagnosis of cancer is important for the outcome; last decades, the introduction of nanotechnology-based carriers, which can serve as both imaging and therapeutic modalities, has risen. Although the combination of imaging and drug delivery for targeting cancer is a hopeful field, it is still under investigation and has not met clinical standards. Nanotheranostics, as they are also referred to, can combine both imaging and delivery and improve the survival rates and overall quality of life of patients. Would cancer patients have a chance to live a normal life if nano theranostics were incorporated into the daily clinical oncology practice? This review tries to answer this question by providing the most current applications of nanotheranostics targeting different types of cancer and summarizing their most significant characteristics.

Polymer based Gels: Recent and Future Applications in Drug Delivery Field.

BACKGROUND: Currently, there is ongoing research in the pharmaceutical technology field to develop innovative drug delivery systems with improved therapeutic efficacy. OBJECTIVES: Although there is a high need for new drug molecules, most scientists focus on the advancement of novel pharmaceutical formulations since the present excipients lack important properties such as low release rate leading to repeated dosing. Aside from this, pharmaceutical technologists aim to develop drug formulations that can target specific organs and tissues, lowering the possibility of adverse effects. METHODS: This review aims to cover the different polymer-based gel types, the development and characterization methods, as well as applications thereof. Finally, the recent advancements and future perspectives focusing on radiolabeled gels will be addressed. RESULTS: In the last decades, polymer based pharmaceutical gels have shown attractive properties and therefore have raised the attention of pharmaceutical scientists. Gels are either chemically or physically cross-linked networks that can absorb fluids such as water (hydrogels), oil (organogels) and even air(aerogels). A variety of polymers, either synthetic or natural, have been employed as components for the gels. Stimuli-responsive gels based on stimuli-sensitive polymers are among the most studied gel class of last years. CONCLUSION: The use of polymer-based gels as drug delivery systems would be beneficial for targeting numerous diseases.

Phytochemical Compounds Loaded to Nanocarriers as Potential Therapeutic Substances for Alzheimer's Disease-Could They be Effective?

Alzheimer's disease accounts for a high percentage of dementia cases in elderly individuals. This type of brain disease is caused by damage to the brain cells affecting the ability of the patients to communicate, as well as their thinking, behavior, and feelings. Although numerous research laboratories focus on advancements in treating Alzheimer's disease, the currently approved pharmacological approaches seem to only alleviate the symptoms. Consequently, there is an urgent need for alternative pharmacological options that can prevent the progressive impairment of neurons. Natural substances were used in ancient times to treat various disorders given their biological activities such as antioxidant, anti-inflammatory, and antiapoptotic properties. Besides, their cost-effectiveness and accessibility to anyone who needs them are their most significant characteristics. Therefore, the possible use of phytochemical compounds for the possible management or even prevention of Alzheimer's disease is currently under investigation. This review article summarizes the present status of Alzheimer's disease diagnosis and underlying mechanisms, the potential phytochemicals and their carriers, along with future perspectives. In the future, natural substances can play a role as an adjunct therapy for neurodegenerative forms of dementia, such as Alzheimer's disease.

Current update on nanoplatforms as therapeutic and diagnostic tools: A review for the materials used as nanotheranostics and imaging modalities.

In the last decade, the use of nanotheranostics as emerging diagnostic and therapeutic tools for various diseases, especially cancer, is held great attention. Up to date, several approaches have been employed in order to develop smart nanotheranostics, which combine bioactive targeting on specific tissues as well as diagnostic properties. The nanotheranostics can deliver therapeutic agents by concomitantly monitor the therapy response in real-time. Consequently, the possibility of over- or under-dosing is decreased. Various non-invasive imaging techniques have been used to quantitatively monitor the drug delivery processes. Radiolabeling of nanomaterials is widely used as powerful diagnostic approach on nuclear medicine imaging. In fact, various radiolabeled nanomaterials have been designed and developed for imaging tumors and other lesions due to their efficient characteristics. Inorganic nanoparticles as gold, silver, silica based nanomaterials or organic nanoparticles as polymers, carbon based nanomaterials, liposomes have been reported as multifunctional nanotheranostics. In this review, the imaging modalities according to their use in various diseases are summarized, providing special details for radiolabeling. In further, the most current nanotheranostics categorized via the used nanomaterials are also summed up. To conclude, this review can be beneficial for medical and pharmaceutical society as well as material scientists who work in the field of nanotheranostics since they can use this research as guide for producing newer and more efficient nanotheranostics.

Promising Polymeric Drug Carriers for Local Delivery: The Case of in situ Gels.

BACKGROUND: At present, the controlled local drug delivery is a very promising approach compared to systemic administration, since it mostly targets the affected tissue. In fact, various drug carriers for local delivery have been prepared with improved therapeutic efficacy. OBJECTIVE: in situ polymer gels are drug delivery systems that not only present liquid characteristics before their administration in body, but once they are administered, form gels due to gelation. Their gelation mechanism is due to factors such as pH alteration, temperature change, ion activation or ultraviolet irradiation. in situ gels offer various advantages compared to conventional formulations due to their ability to release drugs in a sustainable and controllable manner. Most importantly, in situ gels can be used in local drug delivery applications for various diseases. METHODS: This review includes the basic knowledge and theory of in situ gels as well as their various applications according to their administration route. RESULTS: Various natural, semisynthetic, and synthetic polymers can produce in situ polymeric gels. For example, natural polysaccharides such as alginic acid, chitosan, gellan gum, carrageenan etc. have been utilized as in situ gels for topical delivery. Besides the polysaccharides, poloxamers, poly(Nisopropylacrylamide), poly(ethyleneoxide)/ (lactic-co-glycolic acid), and thermosensitive liposome systems can be applied as in situ gels. In most cases, in situ polymeric gels could be applied via various administration routes such as oral, vaginal, ocular, intranasal and injectable. CONCLUSION: To conclude, it can be revealed that in situ gels could be a promising alternative carrier for both chronic and immediate diseases.

In vitro-in vivo evaluation of tetrahydrozoline-loaded ocular in situ gels on rabbits for allergic conjunctivitis management.

Ocular allergy is one of the most common disorders of the eye surface. The conventional eye drops lack of therapeutic efficacy due to low ocular bioavailability and decreased drug residence time on eye surface. Hence, the present research work aimed to formulate, optimize, and evaluate the in situ gel for ophthalmic drug delivery. The prepared in situ gel formulations were evaluated for clarity, pH, gelling capacity, viscosity, osmolality, in vitro release study, and kinetic evaluation. ex vivo corneal permeation/penetration study using goat and in vivo studies on rabbits were also performed. Fourier-transformed infrared spectroscopy was also applied to study possible interactions between drug and polymers. The formulations found to be stable, nonirritant, and showed sustained release of the drug for a period of up to 24 hr with no ocular damage. The developed in situ gels loaded with tetrahydrozoline are alternative and promising ocular candidates for the treatment of allergic conjunctivitis.

Design and characterization of nanocarriers loaded with Levofloxacin for enhanced antimicrobial activity; physicochemical properties, in vitro release and oral acute toxicity

Inorganic and carbon based nanomaterials are widely used against several diseases, such as cancer, autoimmune diseases as well as fungi and bacteria colonization. In this work, Santa Barbara Amorphous mesoporous silica (SBA), Halloysite Nanotubes (HNTs) and Multiwalled Carbon Nanotubes (CNTs) were loaded with fluoroquinolone Levofloxacin (LVF) to be applied as antimicrobial agents. The prepared via adsorption nanocarriers were characterized by Fourier-Transformed Spectroscopy, Scanning Electron Microscopy as well as High Pressure liquid Chromatography. In vitro release studies were carried out using Simulated Body Fluid at 37oC and data analyzed by various kinetic models showing slow dissolution over 12-24 hours. Antimicrobial studies showed improved antibacterial activity against Escherichia coli, Enterococcus faecalis, Listeria monocytogenes, Staphylococcus aureus, and Staphylococcus epidermidis compared to neat nanomaterials. CNTs were found to be the most promising candidates for LVF delivery and they were chosen to be further studied for their acute oral toxicity and histopathological examination using C57/Black mice. Histological examination depicted that drug loading did not affect mice organs morphology as well as hepatocyte degeneration, central vein degeneration and parenchymal necrosis scores. To conclude, the prepared nanomaterials present significant characteristics and can act as antimicrobial drug carriers; CNTs found to be safe candidates when orally fed to mice.

OPHTHALMIC APPLICATIONS of SLN and NLC.

BACKGROUND: The eyes are among the most readily accessible organs in terms of location in the body, yet drug delivery to eye tissues is particularly problematic. The anatomy, physiology and biochemistry of the eye limit the ophthalmic delivery of drugs. Numerous strategies in ophthalmic drug delivery have been made to expand the bioavailability and to prolong the remaining time of drugs treated topically to eye. METHODS: Designing a novel delivery vehicles that can proficiently target the diseased eye tissue, generate high drug levels, and keep sustained and effective concentrations with no or minimum side effects is the main concentration of present examination. One of the encouraging approaches currently is the use of lipidic nanoparticle vehicles categorized by a submicron-meter dimension. Due to their properties and numerous advantages, solid lipid nanoparticles and nanostructure lipid carriers are promising systems for ocular drug delivery. CONCLUSION: The focus of this review is on the recent developments in ophthalmic lipid nanoparticles, the rationale for their use, drug loaded SLNs and NLCs, and the characteristic advantages, limitations of this system and recent studies.

Hypertension in 2017: Update in Treatment and Pharmaceutical Innovations.

Hypertension can be referred to as modern scourge in 2017 and although, it seems that an improvement has been done during the passage of time, the full treatment still remains an unmet achievement for clinicians. Hypertension incidence in Mediterranean countries, especially Greece and Turkey, seems to be increasing irrespective of the expected protective effect of Mediterranean diet. The changed lifestyle and dietary habits of both populations led to advanced cardiovascular events and arteriosclerosis both of which are linked with high blood pressure. From statistic aspect, as in this work reviewed, it has been found out that gender, age, sociodemographic characteristics and geographical location could promote the hypertension prevalence. Given the above, as well as the fact that the current pharmaceutical formulations do not present the optimal results on hypertension management, summing up the ongoing research on hypertension field is in high demand. Consequently, the development of novel solutions for high blood pressure management either with new synthesized drugs or fascinated drug delivery systems is required. Moreover, adopting healthy lifestyle and diet also plays a crucial role against hypertension. This review is aimed at assisting researchers working on hypertension management by summarizing update guidelines, various case reports describing hypertension related with other diseases, current medications and newly synthesized drug delivery systems recently found in literature.

Assessment of Aprotinin Loaded Microemulsion Formulations for Parenteral Drug Delivery: Preparation, Characterization, in vitro Release and Cytotoxicity Studies.

The object of the current study was to prepare novel microemulsion formulations of aprotinin for parenteral delivery and to compare in vitro characteristics and release behaviour of different Technetium-99m ((99m)Tc)-Aprotinin loaded microemulsion formulations. In addition, cytotoxicity of microemulsion formulation was evaluated with cell culture studies on human immortalized pancreatic duct epithelial-like cells. For this aim, firstly, pseudo-ternary phase diagrams were plotted to detect the formulation region and optimal microemulsions were characterized for their thermodynamic stability, conductivity, particle size, zeta potential, viscosity, pH and in vitro release properties. For in vitro release studies aprotinin was labelled with (99m)Tc and labelling efficiency, radiochemical purity and stability of the radiolabeled complex were determined by several chromatography techniques. Radiolabeling efficiency of (99m)Tc-Aprotinin was found over than 90% without any significant changes up to 6 hours after labelling at room temperature. After that, in vitro release studies of (99m)Tc-Aprotinin loaded microemulsions were performed with two different methods; dissolution from diffusion cells and dialysis bags. Both methods showed that release rate of (99m)Tc- Aprotinin from microemulsion could be controlled by microemulsion formulations. Drug release from the optimized microemulsion formulations was found lower compared to drug solution at the end of six hours. According to stability studies, the optimized formulation was found to be stable over a period of 12 months. Also, human immortalized pancreatic duct epithelial-like cells were used to evaluate the cytotoxicity of optimum formulation. Developed microemulsion did not reveal cytotoxicity. In conclusion the present study indicated that the M1-APT microemulsion is appropriate for intravenous application of aprotinin.