Current Nanomedicine - Current Issue

This work is the third part of our initiative to fully describe the internal protein nano environments (NEs) for the three existing types of secondary structure elements (SSE). In our previous work, the NE of both the α-helix and the β-sheet were analyzed. The focus of this and previous research is improving our understanding of the SSEs: α-helices, β-sheets and turns, within protein structures. We found that the structural similarities between turns and α-helices are very high and turns may be considered as the “incomplete” initiation of α-helices. The knowledge we were able to compile during this work might be essential for predicting a tertiary structure of proteins, with higher precision and subsequently being in a more favourable position with regard to designing drugs for certain protein structure/function related diseases. Considering that the formation of secondary structure elements is a crucial step in the general folding of protein 3D structure, an important contribution of this work is augmenting the efficiency of estimating if modelled structures, for example, are predicting SSEs in full agreement to necessary/required/sufficient values of respective SSEs nanoenvironment descriptors. During exactly that modelling phase, preceding the more precise final 3D protein structure construction, our Dictionary of Most Relevant Nanoenvironment Descriptors is able to answer some fundamental questions regarding SSE correctness with regard to nanoenvironment characteristics found to be generally required. Expanding this vision, our current work is part of an effort by our laboratory to create a “dictionary of internal protein nanoenvironments” - DIPN. The ten most studied internal protein nanoenvironments are described in DIPN in physicochemical and structural terms, and this knowledge is now available to be used to aid drug design - probably the most important area of application for the results we are presenting here.

In the current paper, STING´s database of physical-chemical and structural descriptors was used to gather the necessary information to characterize the NE of loops, or, as they are often called, turns. Given that approximately 20% of all protein-type residues form turns, research in this field is essential, and analysis of the obtained results will further contribute to our comprehension of how proteins fold. In addition, the results in this paper will contribute to the better training of algorithms that evaluate the degree of overall protein structure quality and, consequently, structure prediction. This is currently very important given we are witnessing a revolution in algorithms employing artificial intelligence for protein structure prediction. Powered by the STING’s database (wide-ranging protein structure information source), statistical testing was used to retrieve a set of descriptors that fully delineate the NE of turns. By collecting such data, it is then possible to list the variances with respect to the NE of α-helices and β-sheets and, by doing so, establish the most relevant NE descriptors (MRND) for each of the three SSEs.

The results show that the α-helical and β-sheet Nes, as well as the amino acid residue composition, all behave in a similar fashion as a “key and lock” system. In other words, it is necessary for a set of specific descriptors to assume respective specific values (within the bounds of a very definite value region) to construct the specific secondary structure element NE at a certain protein location.

Consequently, there is a set of descriptors that act together and are required to satisfy specific conditions for secondary structure element occurrences. The very same requirement, we found, occurs in the case of turns.

Considering the success of dental implant treatments and their long-term effectiveness, it is important to prevent a series of biological complications such as peri-implant diseases. The development of antimicrobial coatings is known as a promising strategy to overcome these challenges. This study aimed to investigate the durability of simvastatin-loaded gelatin nanoparticle coating on titanium healing abutments.

40 titanium healing abutments were prepared in two groups, including the test group (titanium healing abutments coated with simvastatin nanoparticles, n=20) and the control group (titanium healing abutments without simvastatin nanoparticle coating, n=20). The dip-coating process was then applied to cover the surface of the healing-abutments. The morphology and composition of coatings were evaluated by Scanning Electron Microscope (SEM) and X-Ray Diffraction analysis (XRD), respectively.

The resulting data from SEM and XRD confirmed the successful coating of simvastatin-loaded gelatin nanoparticles on the implant. Based on the Sidak test results, it was observed that the average weight before coating and immediately after coating had a significant difference. Also, the average weight between the initial time (after coating) and the time of 1 day after coating and 30 days after coating was not statistically significant. It means that the coating has been stable for at least 30 days. The difference between the initial weight (after coating) and 60 days after plating was significant. This means that the durability of the coating has decreased until the 60th day.

The resulting data showed that the coating of gelatinous nanoparticles containing simvastatin on the titanium healing abutments was successful, and the durability of the coating lasted for at least 1 month.

Iloperidone is a second-generation antipsychotic drug approved by USFDA for the treatment of acute schizophrenia in adults. Iloperidone shows poor oral bioavailability of about 36% as it undergoes extensive presystemic elimination. Benefits of nasal delivery, as an alternative approach, include non-invasiveness, accessibility, ease of administration and better compliance as compared to intravenous route. Delivery in small nasal volumes can be strengthened using drug nanosuspensions.

The objective of this study is to develop and evaluate Iloperidone nanosuspensions for nasal delivery to improve effectiveness in treating schizophrenia.

Iloperidone nanosuspensions containing Poloxamer 188 as stabilizer, Methocel K15M as mucoadhesive polymer and Gellan gum as in situ gelling agent were prepared by wet milling. Process parameters such as the number of zirconium beads and rotations per minute were optimized to prepare nanosuspensions. The nanosuspensions were evaluated for particle size distribution, polydispersity, zeta potential, in vitro release, ex-vivo permeation and motor activity using animal models.

The developed Iloperidone nanosuspensions showed average particle size and polydispersity index of 268.1 ± 2 nm and 0.362 ± 0.2, respectively and zeta potential of -19.2 ± 0.2 mV. In vitro release studies exhibited more than 80% drug release at the end of 6 hours, while ex-vivo studies indicated a greater percentage of drug from the nanosuspensions permeating across excised goat nasal mucosa. Studies in animal models depicted significant activity with improved motor response for Iloperidone nasal nanosupensions as compared to oral suspensions.

The present study demonstrated the successful development of Iloperidone nanosuspensions for nasal delivery in the management of schizophrenia and proposed to have commercial potential.

An antibiotic called doxorubicin is produced by the Streptomyces peucetius bacterium, which is a member of the anthracycline drug class and is used in chemotherapy. Usually, doxorubicin is employed to cure solid tumors in children and adult patients. The physical and biological stability of the medicine can be increased by encasing it in nanoparticles, which increases the active pharmaceutical ingredient's bioavailability.

This study aimed to create lungs targeting doxorubicin-loaded biodegradable polymeric nanoparticulate system by utilizing an appropriate method and conducting its evaluation.

The polymeric nanoparticles using biodegradable polymers were prepared by the emulsion polymerization method. Franz- diffusion cells were utilized to conduct in-vitro drug diffusion investigations.

Based on the outcomes of the experiments carried out for the research, polymeric nanoparticles of doxorubicin were prepared utilizing different concentrations of chitosan, Sodium alginate, and PLGA. The visual appearance of doxorubicin polymeric nanoparticles shows homogeneous dispersion with no phase separation form. The percentage yield, % entrapment efficiency, and drug content obtained for the final formulation were 93.43 ± 1.776, 87.31 ± 1.075, and 91.98 ± 0.493, respectively. A size dimension of 174.51 nm with a PDI of 0.242 and zeta potential value of -36.1 mV of prepared nanoparticles demonstrate the stability of the formulation. The presentation of the PNPs of the optimized formulation having 310mg Tween 80 showed in vitro diffusion of 98.93% ± 0.296% and an increased flux rate. Based on the determination coefficients, the Higuchi model (K0 = 20.43 and R²= 0.982) was determined to have the best fit for the release data.

Based on the trials conducted during the investigation, it was determined that the emulsion polymerization technique was best for the fabrication of the polymeric nanoparticles by utilizing different concentrations of chitosan, Sodium alginate, and PLGA. The formulation F6 containing 310 mg Tween 80 suggested improved in vitro diffusion following the Higuchi model throughout all formulations. The findings suggest that a sustained process was responsible for the drug's release from the doxorubicin polymeric nanoparticles.