Emerging molecular mechanisms and genetic targets for developing novel therapeutic strategies for treating bladder diseases

Bladder diseases affect millions of patients worldwide and compromise their quality of life with a substantial economic impact. The not fully understood aetiologies of bladder diseases limit the current diagnosis and therapeutic options to primarily symptomatic treatment. In addition, bladder targeted drug delivery is challenging due to its unique anatomical features and its natural physiological function of urine storage and frequent voiding. Therefore, current treatment options often fail to provide a highly effective, precisely targeted and long-lasting treatment. With the growing maturity of gene therapy, comprehensive studies are needed to provide a better understanding of the molecular mechanisms underpinning bladder diseases and help to identify novel gene therapeutic targets and biomarkers for treating bladder diseases. In this review, molecular mechanisms involved in pathology of bladder cancer, interstitial cystitis and overactive bladder syndrome are reviewed, with focus on establishing potential novel treatment options. Proposed novel therapies, including gene therapy combined with nanotechnology, localised drug delivery by nanoparticles, and probiotics, are discussed in regard to their safety profiles, efficacy, treatment lenght, precise targeting, and in comparison to conventional treatment methods

Microfluidics for pharmaceutical nanoparticle fabrication: the truth and the myth

Using micro-sized channels to manipulate fluids is the essence of microfluidics which has wide applications from analytical chemistry to material science and cell biology research. Recently, using microfluidic-based devices for pharmaceutical research, in particular for the fabrication of micro- and nano-particles, has emerged as a new area of interest. The particles that can be prepared by microfluidic devices can range from micron size droplet-based emulsions to nano-sized drug loaded polymeric particles. Microfluidic technology poses unique advantages in terms of the high precision of the mixing regimes and control of fluids involved in formulation preparation. As a result of this, monodispersity of the particles prepared by microfluidics is often recognised as being a particularly advantageous feature in comparison to those prepared by conventional large-scale mixing methods. However, there is a range of practical drawbacks and challenges of using microfluidics as a direct micron- and nano-particle manufacturing method. Technological advances are still required before this type of processing can be translated for application by the pharmaceutical industry. This review focuses specifically on the application of microfluidics for pharmaceutical solid nanoparticle preparation and discusses the theoretical foundation of using the nanoprecipitation principle to generate particles and how this is translated into microfluidic design and operation

Development of polymeric nanoparticles for gene delivery applications

Recent years have witnessed growing attention toward synthesising polymeric nanoparticles for pharmaceutical and biomedical applications. Therefore, microfluidics was introduced in an effort to advance nanoparticles synthesis and scaling up. However, a profound understanding of the synthesis processing parameters impact on the nanoparticle’s properties is of utmost importance to ensure their successful application. Although various research efforts have demonstrated the capacity of microfluidics to fabricate polymeric nanoparticles, there remains a need for a consistent study to examine the difference between microfluidics and the conventional synthesis methods in terms of nanoparticles properties, limitations, and ease of synthesis. Polymeric nanoparticles have been exploited for gene delivery applications due to their advantages. Therefore, several studies examined the use of polymeric nanoparticles for pDNA/miRNAs delivery to target the molecular mechanisms underlying disease development. Osteoarthritis is among these diseases with no effective treatments. Therefore, several studies have focused on explaining the molecular mechanisms underlying osteoarthritis development and the role of miRNAs to address the potential gene targets that could be targeted by miRNAs delivery. However, to the best of our knowledge, no prior studies have examined the use of polymeric NPs for targeting potential gene targets of osteoarthritis by miRNA delivery. The work presented herein offers a comprehensive description and comparison of the different synthesis methods of polymeric nanoparticles, emphasising the advantages and limitations of each synthesis method. In addition, the synthesised nanoparticles were tested for their efficacy in gene delivery applications, including pDNA delivery, to examine the impact of the nanoparticle’s properties on their transfection efficiency and miRNA-140 for targeting the molecular mechanisms underpinning osteoarthritis. The work conducted herein resulted in fabricating novel polymeric NPs that can efficiently deliver miRNA-140 to the chondrocytes to restore homeostasis by regulating the expression of FZD6, ADAMTS5, and MMP 13, three of the well-identified potential gene targets in osteoarthritis