Andrzej Polski

Novel Antibacterial Compounds and their Drug Targets - Successes and Challenges

Infectious diseases are one of the most important and urgent health problems in the world. According to the World Health Organization (WHO) statistics, infectious and parasitic diseases are a cause of about 16% of all deaths worldwide and over 40% of deaths in Africa. A considerable progress that has been made during last hundred years in the fight against infectious diseases, in particular bacterial infections, can be attributed mainly to three factors: (1) the general improvement of living conditions, in particular sanitation; (2) development of vaccines and (3) development of efficient antibacterial drugs. Although considerable progress in reduction of the number of cases of bacterial infections, especially in lethal cases, has been made, continued cases and outbreaks of these diseases persist, which is caused by different contributing factors. Indeed, during last sixty years antibacterial drugs were used against various infectious diseases caused by bacterial pathogens with an undoubtable success. The most fruitful period for antibiotic development lasted from 40s to 60s of the last century and resulted in the majority of antibiotics currently on the market, which were obtained by screening actinomycetes derived from soil. Although the market for antibacterial drugs is nowadays greater than 25 billion US dollars per year, novel antibacterial drugs are still demanded due to developed resistance of many pathogenic bacteria against current antibiotics. In the last five years, one can observe a dramatic increase in cases of resistant bacteria strains (e.g. Klebsiella pneumoniae and E. coli) which are responsible for difficult to treat pneumonia and infections of urinary tract. The development of resistant bacteria strains is a side effect of antibiotic application for treatment: the infections become untreatable as a result of the existence of antibiotic-tolerant persisters. In this review, we discuss the challenges in antibacterial drug discovery, including the molecular basis of drug resistance, drug targets for novel antibacterial drugs, and new compounds (since year 2010) from different chemical classes with antibacterial activity, focusing on structure-activity relationships.

Nanocarriers for Photosensitizers for Use in Antimicrobial Photodynamic Therapy

Antimicrobial photodynamic therapy (aPDT) employs a photoreactive dye photosensitizer in combination with visible light and molecular oxygen. Following light absorption, the photochemical reactions lead to the generation of reactive oxygen species (ROS). ROS-mediated damage to proteins and lipids impairs function of the bacterial cellular structures and subsequently causes the eradication of microorganisms. aPDT is gaining increasing attention because of the multitargeted nature of the photosensitization process and resulting nonspecific mechanism of action. aPDT is effective against, e.g., bacteria, fungi, yeasts, and parasites including antibiotic-resistant strains. Numerous photosensitizers aggregate in aqueous environments, leading to attenuation of their photochemical activity and hindering of their cell internalization. Nanocarriers improve photosensitizer internalization by microbial cells and enable the biofilm barrier to be crossed, enhancing the inactivation of kinetics. Some nanocarriers improve photosensitizers’ ROS yield or act as photosensitizers themselves. This chapter aims to present the advantages of various nanoparticulate delivery systems for photosensitizers and to review different delivery strategies.

Influence of different excipients on the properties of hard gelatin capsules with metamizole sodium

Abstract Metamizole is an effective non-opioid analgesic drug used in the treatment of acute and chronic pain. Due to induced potentially life-threatening blood disorders, metamizole was withdrawn from market in many parts of the world, however, it is one of the most popular analgesics in Poland that is available as an over the counter drug. Patients tend to prefer capsules over tablets, as they are easier to swallow and taste better. The powder-filled capsules also have greater bioavailability and require less excipients, as compared to tablets. Polymic excipients are mainly used in capsule filling, and have influence upon the physico-chemical properties of the hard gelatin capsules and the powder formulation. The aim of the study was to determine whether various combinations of polymers impact the disintegration time and pharmaceutical availability of hard gelatin capsules with metamizole sodium. The results of our work demonstrated that the 80% of all active substance was released in all tested formulations within 15 minutes. Herein, the capsule containing lactose monohydrate had the longest release (4% after 2 min.), while capsules containing mannitol had the fastest release (81.2% after 2 min.). Moreover, the addition of HPMC to capsules with lactose brought about a slight increase in the metamizole release rate, while the addition of PVP 30 to capsules with microcrystalline cellulose slightly accelerated release. This data suggests that the use of different polymers in capsules formulation brings about changes in the physical properties of powders and modifies the release profile of metamizole. In our study, the most preferred formulation was one containing microcrystalline cellulose (good powder properties and fairly fast release).

The effect of a combined choline salicylate and cetalkonium chloride gel on particular strains of Pseudomonas aeruginosa, Staphylococcus spp. and Streptococcus spp.

Abstract The ongoing control of virulent bacteria strains is a challenge for today’s medicine. An example of this, is one widely used drug employed in treating less serious external oral and ocular bacterial infections. This is a gel containing both cetalkonium chloride and choline salicylate. However, whether in the era of expanding bacterial resistance this gel is still effective, is not clear. Hence, in our work, its antibacterial effect was studied against 13 strains of Pseudomonas aeruginosa, 6 strains of Staphylococcus spp. and 6 strains of Streptococcus spp. drawn from the collection of the Department of Microbiology, Virology and Immunology, Kazakh National Medical University, as well as against 30 strains of Staphylococcus spp. recently isolated from Kazakh medical students. This work demonstrated that Pseudomonas aeruginosa was insensitive to this preparation in all samples, while the sensitivity of Staphylococcus spp. and Streptococcus spp. was almost halved, compared to untreated samples. An interesting discovery was the greater resistance of strains obtained from student volunteers than from the collection. However, despite the evident resistance of some strains to the combined cetalkonium chloride and choline salicylate gel, we put forward that it can still be used in less serious external bacterial infections.

A brief analysis of patients suffering from stomach or duodenal ulcers in Almaty hospital №1

Abstract Peptic ulcers are a serious problem worldwide, and affect about 4 million people each year. Their etiology is connected with the presence of Helicobacter pylori, the act of smoking, drinking alcohol, being stress, and taking excessively nonsteroidal anti-inflammatory drugs, as well as steroids. The most common symptoms are abdominal pain, nausea, chest pain and fatigue, while less frequent symptoms include vomiting and weight loss. Helicobacter pylori is responsible for about 80% of gastric and 90% of duodenal ulcer cases. In this work, an analysis is made of a correlation between stomach or duodenal ulcer and gender, residence and number of patients hospitalized in the Almaty hospital №1, from 2009-2012, in order to learn about trends in the incidence of these diseases in Kazakhstan. A total number of 950 patients with stomach and duodenal ulcers, in 2009-2012, were questioned. The patient’s residence, gender and stomach or duodenal ulcer problem were taken into account in the study. The result of this work reveals that the largest amount of hospitalized patients suffering from stomach or duodenal ulcers came from urban areas. Moreover, more women than men suffered from peptic ulcers. Furthermore, the number of patients admitted to the hospital due to duodenal ulcers did not show any variation throughout the study. However, the least number of patients suffering from gastric ulcers was noticed in December 2009, and the greatest was in October and November 2011. The obtained data show that ulcers are a serious problem in Kazakhstan.

Release Kinetics of Papaverine Hydrochloride from Tablets with Different Excipients

Abstract The influence of excipients on the disintegration times of tablets and the release of papaverine hydrochloride (PAP) from tablets were studied. Ten different formulations of tablets with PAP were prepared by direct powder compression. Different binders, disintegrants, fillers, and lubricants were used as excipients. The release of PAP was carried out in the paddle apparatus using 0.1 N HCl as a dissolution medium. The results of the disintegration times of tablets showed that six formulations can be classified as fast dissolving tablets (FDT). FDT formulations contained Avicel PH 101, Avicel PH 102, mannitol, (3-lactose, PVP K 10, gelatinized starch (CPharmGel), Prosolv Easy Tab, Prosolv SMCC 90, magnesium stearate, and the addition of disintegrants such as AcDiSol and Kollidon CL. Drug release kinetics were estimated by the zero- and first-order, Higuchi release rate, and Korsmeyer-Peppas models. Two formulations of the tablets containing PVP (K10) (10%), CPharmGel (10% and 25%), and Prosolv Easy Tab (44% and 60%) without the addition of a disintegrant were well-fitted to the kinetics models such as the Higuchi and zero-order, which are suitable for controlled- or sustained-release.

Review on analgesic effect of co-administrated ibuprofen and caffeine

Abstract Pain is a symptom of many diseases and significantly affects the quality of life, so researchers are constantly seeking new substances to be used as analgesics. Other, easier way is to combine already known drugs which cause synergistic effects greater than additive, so that probability of drug-specific side effects can be reduced. Researchers showed that caffeine can be an effective analgesic adjuvant enhancing antinociceptive effect of ibuprofen in animals and humans. By using modern drug technology methods tablets containing well-soluble ibuprofen salt and caffeine can be easily prepared. Thanks to that combination, the therapeutic dose of ibuprofen can be lowered and the side effects may be reduced.