Therapeutic applications of capsaicin in humans to target conditions of the respiratory system: A scoping review.

BACKGROUND: Various studies have explored potential therapeutic applications of capsaicin in human medicine, for example in pain, obesity, cancer, cardiovascular and respiratory disease. The aim of this scoping review was to identify and chart available evidence on therapeutic applications of capsaicin in humans using any mode of capsaicin delivery to treat conditions of the respiratory system. METHODS: Electronic bibliographic databases (Web of Science, PubMed, Medline, ScienceDirect, Embase, Scopus) were searched from inception to 2021 to identify experimental studies reporting clinical outcomes of therapeutic applications of capsaicin. Studies with or without control group published in peer-reviewed journals were included. Animal studies, studies of human cell lines, and physiological proof of concept studies were excluded. Reviewer pairs independently double-screened 2799 search results for inclusion. RESULTS: Twenty-three original studies were included. Capsaicin has been investigated for the treatment of non-allergic rhinitis (n = 15), nasal polyposis (n = 3), allergic rhinitis (n = 2), unexplained chronic cough (n = 2), and prevention of aspiration pneumonia (n = 1). Modes of delivery included intranasal application (nasal spray, soaked pads, solution), inhalation, ingestion, and aural ointment. Seventeen studies reported positive effects of capsaicin on clinical outcomes for rhinitis, nasal polyposis, chronic cough, and pneumonia. Sixteen studies reported on the safety of capsaicin, with no reports of significant adverse events and overall fair to good patient acceptability. CONCLUSION: While the evidence identified in this review has limited implications for clinical practice, studies support the general safety of capsaicin as administered in these studies and highlight emerging strands of research and clinical hypotheses which warrant further examination.

Fructose malabsorption: causes, diagnosis and treatment.

This review intends to act as an overview of fructose malabsorption (FM) and its role in the aetiology of diseases including, but not limited to, irritable bowel syndrome (IBS) and infantile colic and the relationship between fructose absorption and the propagation of some cancers. IBS results in a variety of symptoms including stomach pains, cramps and bloating. Patients can be categorised into two groups, depending on whether the patients' experiences either constipation (IBS-C) or diarrhoea (IBS-D). FM has been proposed as a potential cause of IBS-D and other diseases, such as infantile colic. However, our knowledge of FM is limited by our understanding of the biochemistry related to the absorption of fructose in the small intestine and FM's relationship with small intestinal bacterial overgrowth. It is important to consider the dietary effects on FM and most importantly, the quantity of excess free fructose consumed. The diagnosis of FM is difficult and often requires indirect means that may result in false positives. Current treatments of FM include dietary intervention, such as low fermentable oligo-, di-, monosaccharides and polyols diets and enzymatic treatments, such as the use of xylose isomerase. More research is needed to accurately diagnose and effectively treat FM. This review is designed with the goal of providing a detailed outline of the issues regarding the causes, diagnosis and treatment of FM.

3DP Printing of Oral Solid Formulations: A Systematic Review.

Three-dimensional (3D) printing is a recent technology, which gives the possibility to manufacture personalised dosage forms and it has a broad range of applications. One of the most developed, it is the manufacture of oral solid dosage and the four 3DP techniques which have been more used for their manufacture are FDM, inkjet 3DP, SLA and SLS. This systematic review is carried out to statistically analyze the current 3DP techniques employed in manufacturing oral solid formulations and assess the recent trends of this new technology. The work has been organised into four steps, (1) screening of the articles, definition of the inclusion and exclusion criteria and classification of the articles in the two main groups (included/excluded); (2) quantification and characterisation of the included articles; (3) evaluation of the validity of data and data extraction process; (4) data analysis, discussion, and conclusion to define which technique offers the best properties to be applied in the manufacture of oral solid formulations. It has been observed that with SLS 3DP technique, all the characterisation tests required by the BP (drug content, drug dissolution profile, hardness, friability, disintegration time and uniformity of weight) have been performed in the majority of articles, except for the friability test. However, it is not possible to define which of the four 3DP techniques is the most suitable for the manufacture of oral solid formulations, because the selection is affected by different parameters, such as the type of formulation, the physical-mechanical properties to achieve. Moreover, each technique has its specific advantages and disadvantages, such as for FDM the biggest challenge is the degradation of the drug, due to high printing temperature process or for SLA is the toxicity of the carcinogenic risk of the photopolymerising material.

Additive Manufacturing Technologies for Drug Delivery Applications.

Patient to patient variability is one of the issues when administering medications to individuals with different health conditions, pharmacokinetic, age, fitness, gender, and race. This requires introducing smart and personalised drug delivery systems with controlled release profile manufactured using novel approaches. Additive manufacturing (AM) provides opportunities such as full customisation, design freedom, and on-site manufacturing, and materials recycling. As a result, the academic and industrial demand for additive manufacturing for drug delivery has been continuously increasing and showing impressive results for a wide range of products. This paper provides an extensive overview of AM technologies and their applications for drug delivery. The review discusses AM technologies including their working principles, processed materials, as well as current progress in drug delivery to produce personalized dosages for every patient with controlled release profile. AM potentials, industrial scale, and challenges are investigated with regards to practice and industrial applications. The paper covers novel possibilities of AM technologies and their pharmaceuticals applications, which indicate a promising healthcare future.

Adherence of Pseudomonas aeruginosa onto surfactant-laden contact lenses.

There is an immense research interest to utilise contact lens (CLs) as a popular platform for ocular drug delivery. However, CLs are the major predisposing factors of bacterial keratitis which is commonly caused by adhesion of microbes such as Pseudomonas aeruginosa and Staphylococcus epidermidis. The aim of the current study is to explore the effect of surfactants; Poloxamer 188, Polysorbate 80 and Tetronic® 90R4 (at 0.25% - 3% v/v) on the characteristics of CLs and on the adhesion abilities of Pseudomonas aeruginosa to the lenses' surfaces. CLs were formulated using a hydrophilic monomer; 2-hydroxyethyl methacrylate (HEMA) together with silicone-based polymer such as Poly dimethyl siloxane (PDMS) or 3,3,3-trifluoropropylsilane (FSA) then lenses were polymerized under UV light. The formulated CLs with surfactants were found to have an increased equilibrium water content (EWC) due to hydrophilic moiety present in surfactants. A relationship was deduced between EWC and surface contact angle of lenses containing surfactants; where an increased EWC was associated with a decrease in contact angle reflecting a more hydrophilic surfaces of CLs. Apart from the 3% Polysorbate 80 (p < .0001) CLs, all other formulations had light transmission values over 80%. Lenses with surfactants were found to have lower bacterial ATP concentration than lenses without surfactants. Poloxamer 188 in FSA lenses reduced bacterial adhesion from 4.22 × 10-4 ±â€¯1.30 × 10-4 pM to 1.03 × 10-4 ±â€¯4.86 × 10-5 pM, a reduction by 75.59% when compared to the control lenses (p = .002). Moreover, 1% Tetronic® 90R4 in PDMS showed a reduction by 57.17% in ATP concentration. Polysorbate 80 in FSA exhibited the least bacterial adhesion with an average bacterial ATP concentration of 3.85 × 10-5 ±â€¯2.61 × 10-5 pM; i.e 90.88% less bacterial ATP than control lenses (p = .001). Bioluminescence studies demonstrated a decrease in Pseudomonas aeruginosa adhesion to CLs containing surfactants without impairing the optical and mechanical characteristics of the lenses.

Stainless steel with tailored porosity using canister-free hot isostatic pressing for improved osseointegration implants.

Porous biomedical implants hold great potential in preventing stress shielding while improving bone osseointegration and regeneration. In this paper, a novel approach is introduced to control the porosity of 316L stainless steel implants by using canister-free hot isostatic pressing (CF-HIPing). The proposed approach uses cold isostatic pressing (CIPing) to generate powder compacts with various particle sizes, followed by CF-HIPing. 316L stainless steel samples with controlled porosity, and mechanical and biological properties were successfully achieved. The results showed a significant increase in the samples' porosity with increasing powder size. Porous structures with a strength of 108-360 MPa, Vickers hardness of 25-49 HV and elastic modulus between 17 and 50 GPa were produced using a particle size range of 5-50 µm. The effect of samples with various porosities on the in vitro response of mouse pre-osteoblastic cells in terms of toxicity and proliferation was studied. All samples showed that they had a minimal toxic effect on the osteoblasts. Samples with low porosity, prepared using a particle size of 5 µm, were believed to hinder the transport of nutrients and oxygen to the cells and hence had lower proliferation. In addition, samples prepared using a particle size range of 16-50 µm were associated with an increased proliferation and are therefore expected to improve the rate of bone osseointegration.

Genomic evaluation during permeability of indomethacin and its solid dispersion.

Drug resistance was first identified in cancer cells that express proteins known as multidrug resistance proteins that extrude the therapeutic agents out of the cells resulting in alteration of pharmacokinetics, tissue distribution, and pharmacodynamics of drugs. To this end studies were carried out to investigate the role of pharmacological inhibitors and pharmaceutical excipients with a primary focus on P-glycoprotein (P-gp). The aim of this study was to investigate holistic changes in transporter gene expression during permeability upon formulation of indomethacin as solid dispersion. Initial characterization studies of solid dispersion of indomethacin showed that the drug was dispersed within the carrier in amorphous form. Analysis of permeability data across Caco-2 monolayers revealed that drug absorption increased by 4-fold when reformulated as solid dispersion. The last phase of the work involved investigation of gene expression changes of transporter genes during permeability. The results showed that there were significant differences in the expression of both ATP-binding cassette (ABC) transporter genes as well as solute carrier transporter (SLC) genes suggesting that the inclusion of polyethylene glycol as well as changes in molecular form of drug from crystalline to amorphous have a significant bearing on the expression of transporter network genes resulting in differences in drug permeability.

Systems biology approach to study permeability of paracetamol and its solid dispersion.

Physiological changes that take place at cellular level are usually reflective of their level of gene expression. Different formulation excipients have an impact on physiological behavior of the exposed cells and in turn affect transporter genes, enterocyte-mediated metabolism and toxicity biomarkers. The aim of this study was to prepare solid dispersion of paracetamol and evaluate genetic changes that occur in Caco-2 cell lines during the permeability of paracetamol alone and paracetamol solid dispersion formulations. Paracetamol-PEG 8000 solid dispersion was prepared by melt fusion method and the formulation was characterised using differential scanning calorimetry (DSC), scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR). Formulation of solid dispersion resulted in the conversion of crystalline drug into an amorphous form. Permeability studies showed that paracetamol absorption was higher from the solid dispersion formulation. DNA microarrays analysis was carried out in order to investigate the involvement of any efflux/uptake transporters in paracetamol or its solid dispersion permeability. Neither transporter carriers nor efflux proteins were found to be involved in the absorption of paracetamol or its PEG solid dispersion. Gene expression analysis established that paracetamol toxicity was potentially reduced upon formulation into solid dispersion when ATP binding cassette (ABC) and solute carrier transporter (SLC) genes were analyzed.