Recent Patents on Anti-Infective Drug Discovery - Volume 13, Issue 2, 2018

Background: Acne is a multifactorial skin disease associated with pilosebaceous unit and caused by bacteria Propionibacterium acnes and Acne vulgaris. Near about 95% people throughout the world suffer from acne at some point in their life span. This disease is more prominent in adults compared to neonates and prepubescent children. Conventionally it is treated with either creams or gels having large number of side effects on patients. Methods: We searched about recent advancements in the use of nanotechnological carriers for effective treatment of acne. We focused on the use of liposomes, niosomes, microemulsions, microsponge, microspheres, and nanoparticles to improve anti-acne therapy. Patents regarding use of nanocarrier systems to eliminate acne were also discussed in this review. Results: The encapsulation of anti-acne drugs in various nanotechnological carriers improve their efficacy and reduce side effects. These carriers show controlled drug release and improved drug penetration even upto pilosebaceous unit of skin. Local tolerability of anti-acne molecules can be improved by adjusting the concentration in nanotechnological carriers. Conclusions: Nanotechnological carriers have opened a new window to design novel, effective and low dose systems for effective eradication acne disease. However, very few nanocarrier based formulations are available in market for topical use and much progress is required in this field to improve anti-acne therapy.

Background: Topical infections, involving a number of diseases such as impetigo, eczema, pustular acne, psoriasis and infected seborrheic dermatitis are one among the many challenges to health which stand out for their profound impact on human species. The treatment of topical infections has always been a difficult proposition because of the lack of efficacy of existing anti-infectives, longer period of treatment and yet incomplete recovery. The increasing emergence of antibiotic resistant bacterial strains like Staphylococcus aureus, Methicillin-Resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa undermines the need for the development of new delivery systems to enhance the therapeutic efficacy of existing topical anti-infectives. Methods: The application of nanotechnology to medicine, or nanomedicine, is rapidly becoming a major driving force behind ongoing changes in the anti-infective field because of its interaction at the sub-atomic level with the skin tissue. The latter, in the current scenario, points towards vesicular carriers like liposomes, lipidic nanoparticles and silver nanoparticles. as the most promising drug delivery solutions for topical infection disorders. These have exhibited immense significance owing to their uniqueness to facilitate the interactions at interfaces with the barrier membranes. Results: The present review summarizes the emerging efforts in combating topical infections particularly using nanomedicine based delivery systems as new tools to tackle the current challenges in treating infectious diseases. Besides, compiling various research reports, this article also includes formulation considerations, mechanisms of penetration and patents reported. Conclusion: Despite the new emerging technologies and delivery systems, efforts are still needed in the right direction to combat this global challenge.

Background: According to the World Health Organization, skin cancer is the most common malignancy for the population. Conventional skin cancer treatment includes surgery and chemotherapy, but many of the chemotherapeutic agents used present undesirable properties. There are a number of patents on topical nano formulation like nanoparticle (US9757453; US9457041), liposomes (US2018177726 (A1), has been covered in this review in the treatment of skin cancer. Methods: Encapsulated drugs are advantageous due to such properties as high stability, better bioavailability, controlled drug release, a long blood circulation time, selective organ or tissue distribution, a lower total required dose, and minimal toxic side effects. Today, researchers are constantly developing new formulations to meet unmet needs in the delivery of therapeutic agents for cancer therapy and diagnosis, respectively. Results: Of particular interest here are lipid-based nanoformulations that are formulated from varieties of lipid and other chemical components that act collectively to overcome biological barriers, in order to preferentially accumulate in or around disease-target cells for the functional delivery of therapeutic agents. The article deals with the recent development of nano-sized topical lipid formulation approaches to treat skin cancer. Conclusion: We focus especially on the topical lipid formulation approaches combined with chemotherapy, a field which specialises in target specificity, drug release control, and realtime monitoring with the goal being to diminish unwanted side effects and their severity, achieving a cheaper treatment and a generally more efficient chemotherapy.

Background: Hospital wastewater has a high amount of both organic and inorganic matter, as well as high densities of living organisms, including pathogenic, and environmental bacteria. It has been suggested that genes encoding resistance to an antibiotic can be located together with heavy metals resistance genes on either the same genetic structure (plasmid) or different genetic structures within the same bacterial strain. Resistance transfer is mainly attributed to conjugation since many antimicrobial resistance genes are situated on mobile elements, such as plasmids and conjugative transposons, whereas renovation and transduction are usually more limited. Our study confirmed the flow of resistance genes between indigenous and foreign organisms and indicated the possibility of resistance transfer from environmental reservoirs to pathogenic strains, which should be underlined in the future. The recent patents on drug resistance (US20030130169, WO/2001/060387, WO/2016/151092) and gene transfer (JP2003189855, JP2010094090), helped in this study. Methods: Water samples were collected from three different sites of hospital wastewater. Isolation of Gram-negative bacteria from hospital wastewater samples was done using the standard microbial procedure. The heavy metal resistance was determined by the minimum inhibitory concentration (MIC) against the test bacterial strain by spot plate method. The antibiotic resistance was determined by a standard disc diffusion technique. The bacterial resistance transfer studies were determined between donor and recipient strain in nutrient as well as wastewater. The antibiogram and MIC of the donors and transconjugants were studied by above-described methods. Results: A high number of Gram-Negative Bacterial Isolates (GNB) exhibited antibiotic and metal resistance transfer into E. coli K-12 and similar GNB isolates in nutrient broth as compared to wastewater. The microbial conjugation experiments showed that a high percentage of multi-resistant GNB (75% and 66%) was able to transfer their single or multidrug resistance patterns to E. coli K-12 among antibiotic while 58%, 66% of the multiresistant isolates were able to transfer their single or multi-metal resistance patterns to E. coli K-12 among metal in nutrient medium and wastewater, respectively. In the present conjugation study, 97.5% and 70% of the total tested GNB isolates were able to transfer an antibiotic-resistant marker to recipient GNB in both the medium (nutrient medium and wastewater), whereas 92.5% and72.5% of the isolates were able to transfer metal resistant marker to recipient GNB in nutrient medium and wastewater from all the site tested. The higher (6.8x10-1 and 5.9x10-1) frequency of transfer was observed among antibiotic and metal while the lower frequency of transfer was (7.0x10-3 and 2.0x10-3) exhibited against antibiotic and metal in both the medium from the entire site tested, respectively. Conclusion: We can recommend that the hospital water is heavily polluted with several types of antibiotics, toxic metals as well as the potentially hazardous bacterial flora because of their capacity to resist one or the other well known antibiotic and chemotherapeutic agents. These studies provide evidence that a wide variety of clinically important antibiotic and metal resistance genes is mobile within aquatic bacterial communities one step ahead of the above, we can envisage the alarming situation prevailing in our system and surrounding in the light of transmissible nature of R-plasmids.

Background: Rising rates of antimicrobial resistance among Enterobacteriaceae limit the use of reliably active forms of available drugs. The aim of this study was to investigate the prevalence of fosfomycin (US6794490B2) resistance gene among ESBL producing isolates in Iran. Method: We tested 355 isolates of Enterobacteriacea collected from various clinical samples including urine, wounds, blood and other sources during June 2016 to July 2017. Antibiotic sensitivity and Extended Spectrum Beta Lactamase (ESBL) production were tested using agar dilution method according to the Clinical and Laboratory Standards Institute (CLSI) guidelines. ESBL genes (blaTEM, bla SHV,bla CTX-M), plasmid-encoded fosfomycin resistance genes (fosA, fosB, fosA3 and fosC2) and chromosomal mutations (murA, glpT, uhpT) were detected by Polymerase Chain Reaction (PCR). Results: In this study, 151 of the 355 isolates were ESBL-positive. blaCTX-M (77%) was the most common gene followed by blaSHV (70%) and blaTEM (58%), either alone or in combination. Eighty nine percent (132/151) of the ESBL-positive isolates were MDR. Antimicrobial susceptibility rates were higher for fosfomycin (92.8%) and imipenem (35.5%) among ESBL-positive isolates. None of the ESBL- positive isolates harbored any mutations or plasmid-mediated fosfomycin resistance determinants. Conclusion: In conclusion, fosfomycin showed good antimicrobial activity against multidrug resistance ESBL- positive Enterobacteriaceae.