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This study aims to develop sorafenib-loaded self-assembled nanoparticles (SFB-SANPs) using the combined approach of artificial neural network and design of experiments (ANN-DoE) and to compare it with other machine learning (ML) models. The central composite design (CCD) and ML algorithms were used to screen the effects of concentrations of both the polymers (polyethyleneimine and fucoidan) on the outcome responses, i.e., particle size and entrapment efficiency with defined constraints. The prediction from different ML models (bootstrap forest, K-nearest neighbors, artificial neural network, generalized regression-lasso and support vector machines) were compared with ANN-DoE model. The ANN-DoE model showed better accuracy and predictability and outperformed all the other models. This depicted that the concept of using ANN and DoE combination approach provided the best, uncomplicated and cost-effective way to optimized the nanoformulations. The optimized formulation generated from the ANN-DoE combined model was further evaluated for characterization and anticancer activity. The optimized SFB-SANPs were prepared using the polyelectrolyte complexation method with Polyethyleneimine (PEI) as a cationic polymer and fucoidan (FCD) as an anionic. The SFB-SANPs were nanometric in size (280.4 ± 0.089 nm) and slightly anionic in nature (zeta potential = -6.03 ± 0.92 mV) with an encapsulation efficiency of 95.56 ± 0.30 %. The drug release from SFB-SANPs was controlled and sustained in the cancer microenvironment (pH 5.0). The SFB-SANPs were compatible with red blood cells (RBCs), and the % hemolysis was found to be <5.0 %. The anticancer activity of the SFB-SANPs exhibited an IC 50 at 2.017 ± 0.516 μM against MDMB-231 cells, showing a significantly high inhibitory effect on breast cancer cell lines. Therefore, the nanocarriers developed using various ML tools inherit a huge promise in anticancer drug delivery., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: To determine the prevalence of work-related musculoskeletal disorders among dentists., Methods: The cross-sectional study was conducted in Islamabad, Pakistan, from January to March 2023 after approval from the ethics review committee of the Islamic International Dental Hospital, Islamabad, and comprised dentists associated with 4 major dental teaching hospitals in the city. Data was collected using a self-administered questionnaire adapted from literature. Prevalence of work-related musculoskeletal disorders was explored along with its association with variables, like age, gender, experience, designation and history of injury. Data was analysed using SPSS 26., Results: Of the 250 forms distributed, 188 (75.2%) were returned duly filled, while the remaining participants either did not respond or partially filled out the forms. Among the respondents, 64(34%) were males and 124(66%) were females, and the overall prevalence of work-related musculoskeletal disorders was 172(91.5%). There was no significant difference among the variables based on anatomic site-specific data, except the designation variable, with individuals having a history of injury to neck (p=0.027) or shoulder (p=0.001) and those designated as professor (p=0.040) were significantly at risk of developing pain due to work-related musculoskeletal disorders., Conclusions: A significantly high number of dentists were found to have some form of work-related musculoskeletal disorder.

Objective: This article critically reviews the recent search on the use of Small Interfering RNA (siRNA) in the process of gene regulation that has been harnessed to silence specific genes in various cell types, including those involved in diabetes complications., Significance: Diabetes, a prevalent and severe condition, poses life-threatening risks due to elevated blood glucose levels. It results from inadequate insulin production by the pancreas or ineffective insulin utilization by the body. Recent research suggests siRNA could hold promise in addressing diabetes complications., Methods: In this review, we discussed several subjects, including diabetes; its function, and common treatment options. An in-depth analysis of gene silencing method for siRNA and role of siRNA in diabetes, focusing on its impact on glucose homeostasis, diabetic retinopathy, wound healing, diabetic nephropathy and peripheral neuropathy, diabetic foot ulcers, diabetic atherosclerosis, and diabetic cardiomyopathy., Result: siRNA-based treatment has the potential to target specific genes without disrupting several other endogenous pathways, which decreases the risk of off-target effects. In addition, siRNA has the capability to provide long-term efficacy with a single dose which will reduce treatment options and enhance patient compliance., Conclusion: In the context of diabetic complications, siRNA has been explored as a potential therapeutic tool to modulate the expression of genes involved in various processes associated with diabetes-related issues such as Diabetic Retinopathy, Neuropathy, Nephropathy, wound healing. The use of siRNA in these contexts is still largely experimental, and challenges such as delivery to specific tissues, potential off-target effects, and long-term safety need to be addressed. Additionally, the development of siRNA-based therapies for clinical use in diabetic complications is an active area of research., Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-024-01405-7., Competing Interests: Competing interestsThe authors declared no financial interest., (© The Author(s), under exclusive licence to Tehran University of Medical Sciences 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Since the ground-breaking discovery of RNA interference (RNAi), scientists have made significant progress in the field of small interfering RNA (siRNA) treatments. Due to severe barriers to the therapeutic application of siRNA, nanoparticle technologies for siRNA delivery have been designed. For pathological circumstances such as viral infection, toxic RNA abnormalities, malignancies, and hereditary diseases, siRNAs are potential therapeutic agents. However, systemic administration of siRNAs in vivo remains a substantial issue due to a lack of "drug-likeness" (siRNA are relatively larger than drugs and have low hydrophobicity), physiological obstacles, and possible toxicities. This write-up covers important accomplishment in the field of clinical trials and patents specially based of siRNAs using targeting viruses. Furthermore, it offers deep insight of nanoparticle applied for siRNA delivery and strategies to improve the effectiveness of antivirals., (© 2023. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

Drug-drug cocrystalllization is a novel mechanism for effective pharmacological combination therapy. In this work, we have demonstrated the preparation of a drug-drug cocrystal of a hypertension drug (Telmisartan; TEL) with a hyperuricemia drug (Febuxostat; FEB) in 1:1 molar ratio using a solvent evaporation method for the first time. Generally, a multi-component system may yield either a eutectic, salt, and/or a cocrystal. This study adopted a methodical orthogonal framework to analyze the final solid form. A single crystal X-ray structural investigation revealed the formation of a heterosynthon with carboxylic and benzimidazole groups of FEB and TEL, respectively, in the triclinic P-1 space group. ΔpKa of the heterosynthon is ∼1.5, hence, based on the empirical rules, a salt-cocrystal continuum is hypothesized. Further, attenuated total reflectance Fourier transform infrared (ATR-FTIR), and Raman spectroscopy were employed to corroborate the hydrogen bond formation in the heterosynthon (-N---H-O-), which confirmed the propensity for cocrystal formation. An accelerated stability study and an in vitro biorelevant dissolution study of the cocrystal were performed, which demonstrated that it is physiochemically stable, but it resulted in a slower dissolution rate when compared with plain drugs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.)

Oral drug administration is the oldest and widely used method for drug administration. The objectives behind developing an oral drug delivery for the treatment of cancer are to achieve low cost treatment by utilizing novel techniques to target cancer through gut-associated lymphoid tissue (GALT) and to enhance patient comfort and compliance through a hospital-free treatment leading to "Chemotherapy at Home." Unfortunately, due to the physiological environment of the GIT and physicochemical properties of drug candidate, the efficacy of oral drug delivery methods is limited in the treatment of cancer. Due to their low hydrophilicity, high P-gp efflux and restricted intestinal permeability most of the anti-cancer drugs fail to achieve oral bioavailability. The review focuses on the efforts, challenges, opportunities and studies conducted by scientists worldwide on the oral administration of anticancer medications via nanocarriers such as liposomes, SLNs and dendrimers, because of their potential to overcome the epithelial barrier associated with GALT, as well as the applications of different polymers in targeting the cancer. The oral delivery can set newer horizons in cancer therapy to make it more patient friendly., (© 2022. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

The current study investigates the potential for topical delivery of a fluticasone propionate (FP) and levocetirizine dihydrochloride (CTZ)-loaded microemulsion (ME) for the management of atopic dermatitis. Various microemulsion components were chosen based on their solubility and emulsification capabilities, and the ternary phase diagram was constructed. A total of 12 microemulsion formulations were screened for various attributes like vesicle size, polydispersity index, ζ-potential, percent transmittance, density, and pH. The average globule size and ζ-potential of FP and levocetirizine-containing ME were 52.12 nm and -2.98 ζ-potential, respectively. Transmission electron microscopy confirmed the spherical nature of the globules. The developed system not only controlled the release of both drugs but also enhanced the efficacy of the drugs on a rodent model. Histopathological studies confirmed the safety of the developed system. The present findings provide evidence for a scalable and simpler approach for the management of atopic dermatitis., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Neglected tropical disease (NTD) is a set of 20 deadliest endemic diseases which shows its presence in most of the developing countries worldwide. Nearly 1 billion of the population are affected by it and suffered from poverty yearly. These diseases offer their own unique challenges and limitations towards effective prevention and treatment methods. Neglected tropical diseases are severe infections they may not kill the patient but debilitate the patient by causing severe skin deformities, disfigurement and horrible risks for several infections. Existing therapies for neglected diseases suffer from the loopholes like high degree of toxicity, side effects, low bioavailability, improper targeting and problematic application for affected populations. Progress in the field of nanotechnology in last decades suggested the intervention of nanocarriers to take over and drive the research and development to the next level by incorporating established drugs into the nanocarriers rather than discovering the newer drugs which is an expensive affair. These nanocarriers are believed to be a sure shot technique to fight infections at root level by virtue of its nanosize and ability to reach at cellular level. This article highlights the recent advances, rationale, targets and the challenges that are being faced to fight against NTDs and how the novel therapy tactics are able to contribute to its importance in prevention and treatment of NTDs., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Co-crystal is an attractive alternative and a new class of solid forms because that can be engineered to have desired physicochemical properties. Co-crystals have gained considerable attention from the generic pharmaceutical industry after the USFDA released its finalized guidlines in the year 2018 on the regulatory classification of co-crystals. In this review, we discussed how co-crystals could be explored as a potential alternative solid form for the development of a generic product that meets the legal, regulatory, and bioequivalence requirements. In the contents, we discussed in detail concepts such as the selection of coformers, various ways of making co-crystals, the strategy of characterization to discriminate between co-crystal and salt, polymorphism in co-crystals, the aspects of intellectual property and, finally, the regulatory aspects of co-crystals., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Inadequate cleaning of a pharmaceutical manufacturing plant or inadequate purging of the individual pieces of equipment used in multi-product manufacturing or equipment not dedicated to individual products may lead to contamination of the next batch of pharmaceutics manufactured using the same equipment. Challenges for cleaning validation are encountered especially when developing sensitive analytical methods capable of detecting traces of active pharmaceutical ingredients that are likely to remain on the surface of the pharmaceutical equipment after cleaning. A method's inability to detect some residuals could mean that either the method is not sensitive enough to the residue in question or the sampling procedure is inadequate. A sensitive and reproducible reversed-phase, high-performance liquid chromatographic method was developed for the determination of ofloxacin in swab samples. The method for determining ofloxacin residues on manufacturing equipment surfaces was validated in regard to precision, linearity, accuracy, specificity, limit of quantification, and percent recovery from the equipment surface, as well as the stability of a potential contaminant in a cleaning validation process. The active compound was selectively quantified in a sample matrix and swab material in amounts as low as 0.55 ng/mL. The swabbing procedure using cotton swabs was validated. A mean recovery from stainless steel plate of close to 85% was obtained. Chromatography was carried out on a pre-packed Merck (Dermstadt, Germany) Lichrospher model 100 Rp-18 (5.0 microm, 250 mm X 4.0 mm) column using a mixture of sodium lauryl sulfate (0.024% aqueous solution), acetonitrile, and glacial acetic acid (500:480:20,v/v) as the mobile phase at a flow rate of 1.5 mL/min with a column temperature of 35 degrees C and 294 nm detection. The assay was linear over the concentration range of 2 ng/mL to 2000 ng/mL (R approximately 0.99998). The method was validated for accuracy and precision. The stability of ofloxacin in the swab samples was also assessed. In regard to the 10-ppm acceptance criteria in the succeeding batch, the calculated limit was 437 microg/cm2 while according to the 0.1% dosing approach the calculated value was 116 microg/cm2. The calculated recovery values from swab samples were below these acceptable limits during three consecutive cleaning trials. This confirms that the desired level of cleanliness is achieved using the current cleaning procedures, which were consequently validated.