APPLICABILITY OF NANOPARTICLES-HYDROGEL COMPOSITE IN TREATING PERIODONTAL DISEASES AND BEYOND

Nanoparticles-Hydrogel Composite (nanogels) have yielded a surge in the design and development of novel drug delivery systems for the treatment of many ailments, including periodontal disease. The recent innovations in nanotechnological drug carrier systems seem promising, as it provides a means to improve the bioavailability of poorly soluble drugs, formulations of controlled and targeted drug delivery systems, drug release control base on the stimuli response, among others. Several polymeric nanoparticles-hydrogel co-formulations have been investigated during the last few years, mostly using synthetic & natural polymers. Some of the results and rewards achieved from these novel approaches are the use of bioadhesive polymers to achieve prolong drug release, the increment of intra-pocket drug penetration, the enhancement of mechanical properties using chemical crosslinkers and the possibility of loading multiple drugs in a unit delivery system.  Furthermore, these nanotechnological advances have also shown that nanoparticles (NPs) possess great potential as drug carriers in periodontal disease treatment. The future utilization of these advantages will significantly improve dental care. The co-formulation of nanoparticles-hydrogel composite will yield additional benefits that are much greater than ordinary NPs or hydrogels in delivering of drug into the periodontal pockets. The aim of this review article is to summarises updates on the current and future nanotechnological approaches that are being investigated for the treatment of periodontitis, with particular attention to the nanogels, and to identify arenas which its exploration might lead to the development of an effective intra-pocket drug delivery systems for the treatment of periodontal diseases. The review also provided brief applications of nanogels in the management of other diseases.Keywords: Nanocomposite, Hydrogels, Nanoparticles, Nanogels, Periodontal intra-pocket drug delivery system, Nanotechnological approaches

Acquisition of a natural resistance gene renders a clinical strain of methicillin-resistant Staphylococcus aureus resistant to the synthetic antibiotic linezolid.

Linezolid, which targets the ribosome, is a new synthetic antibiotic that is used for treatment of infections caused by Gram-positive pathogens. Clinical resistance to linezolid, so far, has been developing only slowly and has involved exclusively target site mutations. We have discovered that linezolid resistance in a methicillin-resistant Staphylococcus aureus hospital strain from Colombia is determined by the presence of the cfr gene whose product, Cfr methyltransferase, modifies adenosine at position 2503 in 23S rRNA in the large ribosomal subunit. The molecular model of the linezolid-ribosome complex reveals localization of A2503 within the drug binding site. The natural function of cfr likely involves protection against natural antibiotics whose site of action overlaps that of linezolid. In the chromosome of the clinical strain, cfr is linked to ermB, a gene responsible for dimethylation of A2058 in 23S rRNA. Coexpression of these two genes confers resistance to all the clinically relevant antibiotics that target the large ribosomal subunit. The association of the ermB/cfr operon with transposon and plasmid genetic elements indicates its possible mobile nature. This is the first example of clinical resistance to the synthetic drug linezolid which involves a natural resistance gene with the capability of disseminating among Gram-positive pathogenic strains

Fusidic acid/tea-tree oil nanoemulsions : a potentially safe and effective anti MRSA/MSSA topical agent for chronic wound healing

Fusidic acid (FA) is clinically used as an antibacterial agent for the treatment of Gram-positive bacterial infections. It interferes with bacterial protein synthesis, specifically by preventing the translocation of the elongation factor G on the ribosome. In the present work, oil-in-water nanoemulsion (NE) was developed as a carrier for the transdermal delivery of FA. Different oils, surfactants and co-surfactants were screened. The solubility of FA, the emulsifying capacity of the surfactants and phase diagrams for each oil and surfactant mix were constructed. From the analysis, eight stable NE formulations were chosen, and their physicochemical properties were further evaluated. The antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-sensitive Staphylococcus aureus (MSSA) were also evaluated, and cytotoxicity was conducted on HS-27 cell line to determine the safety of the formula. It was found that the NE produced from tea tree oil has the most optimal stability with promising antibacterial activity against MRSA as compared to a commercially available product. The safety profile of the NE was also comparable to the commercial product; thus, the formulated FA-NE is promising for clinical use

Jerantinine A induces tumor-specific cell death through modulation of splicing factor 3b subunit 1 (SF3B1)

Precursor mRNA (pre-mRNA) splicing is catalyzed by a large ribonucleoprotein complex known as the spliceosome. Numerous studies have indicated that aberrant splicing patterns or mutations in spliceosome components, including the splicing factor 3b subunit 1 (SF3B1), are associated with hallmark cancer phenotypes. This has led to the identification and development of small molecules with spliceosome-modulating activity as potential anticancer agents. Jerantinine A (JA) is a novel indole alkaloid which displays potent anti-proliferative activities against human cancer cell lines by inhibiting tubulin polymerization and inducing G2/M cell cycle arrest. Using a combined pooled-genome wide shRNA library screen and global proteomic profiling, we showed that JA targets the spliceosome by up-regulating SF3B1 and SF3B3 protein in breast cancer cells. Notably, JA induced significant tumor-specific cell death and a significant increase in unspliced pre-mRNAs. In contrast, depletion of endogenous SF3B1 abrogated the apoptotic effects, but not the G2/M cell cycle arrest induced by JA. Further analyses showed that JA stabilizes endogenous SF3B1 protein in breast cancer cells and induced dissociation of the protein from the nucleosome complex. Together, these results demonstrate that JA exerts its antitumor activity by targeting SF3B1 and SF3B3 in addition to its reported targeting of tubulin polymerization

Target site modifications in the ribosome as antibiotic resistance mechanisms.

Target site modifications in the ribosome as antibiotic resistance mechanisms

The methyltransferase YfgB/RlmN is responsible for modification of adenosine 2503 in 23S rRNA

A2503 in 23S rRNA of the Gram-negative bacterium Escherichia coli is located in a functionally important region of the ribosome, at the entrance to the nascent peptide exit tunnel. In E. coli, and likely in other species, this adenosine residue is post-transcriptionally modified to m2A. The enzyme responsible for this modification was previously unknown. We identified E. coli protein YfgB, which belongs to the radical SAM enzyme superfamily, as the methyltransferase that modifies A2503 of 23S rRNA to m2A. Inactivation of the yfgB gene in E. coli led to the loss of modification at nucleotide A2503 of 23S rRNA as revealed by primer extension analysis and thin layer chromatography. The A2503 modification was restored when YfgB protein was expressed in the yfgB knockout strain. A similar protein was shown to catalyze post-transcriptional modification of A2503 in 23S rRNA in Gram-positive Staphylococcus aureus. The yfgB knockout strain loses in competition with wild type in a co-growth experiment, indicating functional importance of A2503 modification. The location of A2503 in the exit tunnel suggests its possible involvement in interaction with the nascent peptide and raises the possibility that its post-transcriptional modification may influence such an interaction

The improved dissolution performance of a post processing treated spray-dried crystalline solid dispersion of poorly soluble drugs

<p><b>Context:</b> Solution-mediated transformation has been cited as one of the main problems that deteriorate dissolution performances of solid dispersion (SD). This is mainly attributed by the recrystallization tendency of poorly soluble drug. Eventually, it will lead to extensive agglomeration which is a key process in reducing the dissolution performance of SD and offsets the true benefit of SD system. Here, a post-processing treatment is suggested in order to reduce the recrystallization tendency and hence bring forth the dissolution advantage of SD system.</p> <p><b>Objectives:</b> The current study investigates the effect of a post processing treatment on dissolution performance of SD in comparison to their performances upon production.</p> <p><b>Methods:</b> Two poorly soluble drugs were spray dried into SD using polyvinyl alcohol (PVA) as hydrophilic carrier. The obtained samples were post processing treated by exposure to high humidity, i.e. 75% RH at room temperature. The physical properties and release rate of the SD system were characterized upon production and after the post-processing treatment.</p> <p><b>Results and discussion:</b> XRPD, Infrared and DSC results showed partial crystallinity of the fresh SD systems. Crystallinity of these products was further increased after the post-processing treatment at 75% RH. This may be attributed to the high moisture absorption of the SD system that promotes recrystallization process of the drug. However, dissolution efficiencies of the post-treated systems were higher and more consistent than the fresh SD. The unexpected dissolution trend was further supported by the results intrinsic dissolution and solubility studies.</p> <p><b>Conclusions:</b> An increase of crystallinity in a post humidity treated SD did not exert detrimental effect to their dissolution profiles. A more stabilized system with a preferable enhanced dissolution rate was obtained by exposing the SD to a post processing humidity treatment.</p

Liquid and Solid Self-Emulsifying Drug Delivery Systems (SEDDs) as Carriers for the Oral Delivery of Azithromycin: Optimization, In Vitro Characterization and Stability Assessment

Azithromycin (AZM) is a macrolide antibiotic used for the treatment of various bacterial infections. The drug is known to have low oral bioavailability (37%) which may be attributed to its relatively high molecular weight, low solubility, dissolution rate, and incomplete intestinal absorption. To overcome these drawbacks, liquid (L) and solid (S) self-emulsifying drug delivery systems (SEDDs) of AZM were developed and optimized. Eight different pseudo-ternary diagrams were constructed based on the drug solubility and the emulsification studies in various SEDDs excipients at different surfactant to co-surfactant (Smix) ratios. Droplet size (DS) &lt; 150 nm, dispersity (Đ) &le; 0.7, and transmittance (T)% &gt; 85 in three diluents of distilled water (DW), 0.1 mM HCl, and simulated intestinal fluids (SIF) were considered as the selection criteria. The final formulations of L-SEDDs (L-F1(H)), and S-SEDDs (S-F1(H)) were able to meet the selection requirements. Both formulations were proven to be cytocompatible and able to open up the cellular epithelial tight junctions (TJ). The drug dissolution studies showed that after 5 min &gt; 90% and 52.22% of the AZM was released from liquid and solid SEDDs formulations in DW, respectively, compared to 11.27% of the pure AZM, suggesting the developed SEDDs may enhance the oral delivery of the drug. The formulations were stable at refrigerator storage conditions