The Interplay of Lipid Signaling in Musculoskeletal Cross Talk: Implications for Health and Disease.

The intricate interplay between the muscle and bone tissues is a fundamental aspect of musculoskeletal physiology. Over the past decades, emerging research has highlighted the pivotal role of lipid signaling in mediating communication between these tissues. This chapter delves into the multifaceted mechanisms through which lipids, particularly phospholipids, sphingolipids, and eicosanoids, participate in orchestrating cellular responses and metabolic pathways in both muscle and bone. Additionally, we examine the clinical implications of disrupted lipid signaling in musculoskeletal disorders, offering insights into potential therapeutic avenues. This chapter aims to shed light on the complex lipid-driven interactions between the muscle and bone tissues, paving the way for a deeper understanding of musculoskeletal health and disease.

Nanoparticles and Their Applications in Lipid Signaling.

This chapter provides an overview of the diverse range of applications associated with nanoparticles. The application of nanoparticles in the medical field has garnered considerable attention due to their unique properties and versatile compositions. They have shown promise in the treatment of cancer, fungal and viral infections, and pain management. These systems provide numerous benefits, such as increased drug stability, improved bioavailability, and targeted delivery to specific tissues or cells. The objective of this chapter is to provide a brief analysis of the differences between nanoparticles and lipid particles, focusing particularly on the importance of nanoparticle size and composition in their interactions with lipids. Additionally, the applications of nanoparticles in lipid signaling will be discussed, considering the vital roles lipids play in cellular signaling pathways. Nanoparticles have shown immense potential in the regulation and control of medical pathways. In this case, we will focus on the manufacture of liposomes, a type of nanoparticle composed of lipids. The reason behind the extensive investigation into liposomes as drug delivery vehicles is their remarkable biocompatibility and adaptability. This section will provide insights into the methods and techniques employed for liposome formulation.

Market Needs and Methodologies Associated with Patient Lipidomic Diagnoses and Analyses.

This chapter conducts an in-depth exploration of the impact of musculoskeletal (MSK) disorders and injuries, with a specific emphasis on their consequences within the older population demographic. It underscores the escalating demand for innovative interventions in MSK tissue engineering. The chapter also highlights the fundamental role played by lipid signaling mediators (LSMs) in tissue regeneration, with relevance to bone and muscle recovery. Remarkably, Prostaglandin E2 (PGE2) emerges as a central orchestrator in these regenerative processes. Furthermore, the chapter investigates the complex interplay between bone and muscle tissues, explaining the important influence exerted by LSMs on their growth and differentiation. The targeted modulation of LSM pathways holds substantial promise as a beneficial way for addressing muscle disorders. In addition to these conceptual understandings, the chapter provides a comprehensive overview of methodologies employed in the identification of LSMs, with a specific focus on the Liquid Chromatography-Mass Spectrometry (LC-MS). Furthermore, it introduces a detailed LC MS/MS-based protocol tailored for the detection of PGE2, serving as an invaluable resource for researchers immersed in this dynamic field of study.

Detailed Protocol for Solid-Phase Extraction for Lipidomic Analysis.

Developing robust analytical techniques is a vital phase to facilitate understanding the roles and impacts of various omic profilings in cellular functions. The comprehensive analysis of various biological molecules within a biological system requires a precise sample preparation technique. Solid-Phase Extraction (SPE) has proven to be an indispensable method in lipidomic analysis, providing an uncomplicated and user-friendly technique for extraction and purification of lipid components from complex biological matrices. Of all the factors influencing the reliability and success of SPE, column or adsorbent materials, flow rate, and storage conditions are paramount in terms of their significance. In this chapter, we will discuss in detail the SPE steps for lipidomic analysis in biofluid samples (serum and plasma) and muscle tissues.

Computational Amendment of Parenteral In Situ Forming Particulates' Characteristics: Design of Experiment and PBPK Physiological Modeling.

Lipid and/or polymer-based drug conjugates can potentially minimize side effects by increasing drug accumulation at target sites and thus augment patient compliance. Formulation factors can present a potent influence on the characteristics of the obtained systems. The selection of an appropriate solvent with satisfactory rheological properties, miscibility, and biocompatibility is essential to optimize drug release. This work presents a computational study of the effect of the basic formulation factors on the characteristics of the obtained in situ-forming particulates (IFPs) encapsulating a model drug using a 21.31 full factorial experimental design. The emulsion method was employed for the preparation of lipid and/or polymer-based IFPs. The IFP release profiles and parameters were computed. Additionally, a desirability study was carried out to choose the optimum formulation for further morphological examination, rheological study, and PBPK physiological modeling. Results revealed that the type of particulate forming agent (lipid/polymer) and the incorporation of structure additives like Brij 52 and Eudragit RL can effectively augment the release profile as well as the burst of the drug. The optimized formulation exhibited a pseudoplastic rheological behavior and yielded uniformly spherical-shaped dense particulates with a PS of 573.92 ± 23.5 nm upon injection. Physiological modeling simulation revealed the pioneer pharmacokinetic properties of the optimized formulation compared to the observed data. These results assure the importance of controlling the formulation factors during drug development, the potentiality of the optimized IFPs for the intramuscular delivery of piroxicam, and the reliability of PBPK physiological modeling in predicting the biological performance of new formulations with effective cost management.

Revolutionizing bone regeneration: advanced biomaterials for healing compromised bone defects.

In this review, we explore the application of novel biomaterial-based therapies specifically targeted towards craniofacial bone defects. The repair and regeneration of critical sized bone defects in the craniofacial region requires the use of bioactive materials to stabilize and expedite the healing process. However, the existing clinical approaches face challenges in effectively treating complex craniofacial bone defects, including issues such as oxidative stress, inflammation, and soft tissue loss. Given that a significant portion of individuals affected by traumatic bone defects in the craniofacial area belong to the aging population, there is an urgent need for innovative biomaterials to address the declining rate of new bone formation associated with age-related changes in the skeletal system. This article emphasizes the importance of semiconductor industry-derived materials as a potential solution to combat oxidative stress and address the challenges associated with aging bone. Furthermore, we discuss various material and autologous treatment approaches, as well as in vitro and in vivo models used to investigate new therapeutic strategies in the context of craniofacial bone repair. By focusing on these aspects, we aim to shed light on the potential of advanced biomaterials to overcome the limitations of current treatments and pave the way for more effective and efficient therapeutic interventions for craniofacial bone defects.

Artificial intelligence-assisted development of in situ forming nanoparticles for arthritis therapy via intra-articular delivery.

Intra-articular (IA) injection is grasping much interest due to the poor drug bioavailability at the targeted site of action which minimizes the effect of the orally administered moiety. Based on the integral role of non-steroidal anti-inflammatory drugs (NSAIDs) in the treatment of Rheumatoid Arthritis (RA), much effort is exerted to develop novel localized drug delivery systems to increase their bioavailability and minimize their side effects. Artificial intelligence (AI) is acquiring an increasing role in the design of experiments being an effective tool for saving both time and resources. Hence, the aim of this work was to develop, characterize and optimize targeted in-situ forming nano particles (ISNs) for IA delivery of piroxicam using Design® Expert as an AI-based application where a 33 full factorial experimental design was adopted. Morphological investigation, injectability, rheological studies, Fourier Transform Infrared Radiation (FTIR) as well as biological, histopathological, and biochemical examinations were performed to evaluate the optimized-ISNs. The optimized formulation, exhibiting a nano-sized particle size with a dense core, showed significant improvement in the histopathological findings compared to both the oral solution and the placebo. Additionally, the once-a-week IA administration of the optimized-ISNs proved a significant reduction in the protein expression of both STAT-3 and RANKL and the levels of anti-CCP and MCP-1 by almost 54 and 73%, respectively, coupled with a marked decline in the content of IL-17, MMP-3, NF-κB and TNF-α as compared to the positive control. In conclusion, the use of ISNs for intra-articular injection has demonstrated their effectiveness in piroxicam delivery for RA treatment.