Therapeutic Potential of Nanocarrier Mediated Delivery of Peptides for Wound Healing: Current Status, Challenges and Future Prospective.

Wound healing presents a complex physiological process that involves a sequence of events orchestrated by various cellular and molecular mechanisms. In recent years, there has been growing interest in leveraging nanomaterials and peptides to enhance wound healing outcomes. Nanocarriers offer unique properties such as high surface area-to-volume ratio, tunable physicochemical characteristics, and the ability to deliver therapeutic agents in a controlled manner. Similarly, peptides, with their diverse biological activities and low immunogenicity, hold great promise as therapeutics in wound healing applications. In this review, authors explore the potential of peptides as bioactive components in wound healing formulations, focusing on their antimicrobial, anti-inflammatory, and pro-regenerative properties. Despite the significant progress made in this field, several challenges remain, including the need for standardized characterization methods, optimization of biocompatibility and safety profiles, and translation from bench to bedside. Furthermore, developing multifunctional nanomaterial-peptide hybrid systems represents promising avenues for future research. Overall, the integration of nanomaterials made up of natural or synthetic polymers with peptide-based formulations holds tremendous therapeutic potential in advancing the field of wound healing and improving clinical outcomes for patients with acute and chronic wounds.

Nanotechnology in Orthodontics: Unveiling Pain Mechanisms, Innovations, and Future Prospects of Nanomaterials in Drug Delivery.

Orthodontic pain is characterized by sensations of tingling, tooth discomfort, and intolerance. According to the oral health report, over forty percent of children and adolescents have undergone orthodontic treatment. The efficacy of orthodontic treatment involving braces can be compromised by the diverse levels of discomfort and suffering experienced by patients, leading to suboptimal treatment outcomes and reduced patient adherence. Nanotechnology has entered all areas of science and technology. This review provides an overview of nanoscience, its application in orthodontics, the underlying processes of orthodontic pain, effective treatment options, and a summary of recent research in Nano-dentistry. The uses of this technology in healthcare span a wide range, including enhanced diagnostics, biosensors, and targeted drug delivery. The reason for this is that nanomaterials possess distinct qualities that depend on their size, which can greatly enhance human well-being and contribute to better health when effectively utilized. The field of dentistry has also experienced significant advancements, particularly in the past decade, especially in the utilization of nanomaterials and technology. Over time, there has been an increase in the availability of dental nanomaterials, and a diverse array of these materials have been extensively studied for both commercial and therapeutic purposes.

Biopolymer based nanoparticles and their therapeutic potential in wound healing - A review.

Nanoparticles (NPs) have been extensively investigated for their potential in nanomedicine. There is a significant level of enthusiasm about the potential of NPs to bring out a transformative impact on modern healthcare. NPs can serve as effective wound dressings or delivery vehicles due to their antibacterial and pro-wound-healing properties. Biopolymer-based NPs can be manufactured using various food-grade biopolymers, such as proteins, polysaccharides, and synthetic polymers, each offering distinct properties suitable for different applications which include collagen, polycaprolactone, chitosan, alginate, and polylactic acid, etc. Their biodegradable and biocompatible nature renders them ideal nanomaterials for applications in wound healing. Additionally, the nanofibers containing biopolymer-based NPs have shown excellent anti-bacterial and wound healing activity like silver NPs. These NPs represent a paradigm shift in wound healing therapies, offering targeted and personalized solutions for enhanced tissue regeneration and accelerated wound closure. The current review focuses on biopolymer NPs with their applications in wound healing.

Microbubbles: Revolutionizing Biomedical Applications with Tailored Therapeutic Precision.

BACKGROUND: Over the past ten years, tremendous progress has been made in microbubble-based research for a variety of biological applications. Microbubbles emerged as a compelling and dynamic tool in modern drug delivery systems. They are employed to deliver drugs or genes to targeted regions of interest, and then ultrasound is used to burst the microbubbles, causing site-specific delivery of the bioactive materials. OBJECTIVE: The objective of this article is to review the microbubble compositions and physiochemical characteristics in relation to the development of innovative biomedical applications, with a focus on molecular imaging and targeted drug/gene delivery. METHODS: The microbubbles are prepared by using various methods, which include cross-linking polymerization, emulsion solvent evaporation, atomization, and reconstitution. In cross-linking polymerization, a fine foam of the polymer is formed, which serves as a bubble coating agent and colloidal stabilizer, resulting from the vigorous stirring of a polymeric solution. In the case of emulsion solvent evaporation, there are two solutions utilized in the production of microbubbles. In atomization and reconstitution, porous spheres are created by atomising a surfactant solution into a hot gas. They are encapsulated in primary modifier gas. After the addition of the second gas or gas osmotic agent, the package is placed into a vial and sealed after reconstituting with sterile saline solution. RESULTS: Microbubble-based drug delivery is an innovative approach in the field of drug delivery that utilizes microbubbles, which are tiny gas-filled bubbles, act as carriers for therapeutic agents. These microbubbles can be loaded with drugs, imaging agents, or genes and then guided to specific target sites. CONCLUSION: The potential utility of microbubbles in biomedical applications is continually growing as novel formulations and methods. The versatility of microbubbles allows for customization, tailoring the delivery system to various medical applications, including cancer therapy, cardiovascular treatments, and gene therapy.

A Comprehensive Review on Drug Therapies and Nanomaterials used in Orthodontic Treatment.

Orthodontic treatment typically requires an extended duration of 1-2 years to complete the treatment. Accelerating the rate of tooth movement during orthodontic treatment is essential for shortening the overall treatment duration. After the completion of orthodontic treatment, a prominent concern arises in the form of orthodontic relapse, where the teeth tend to revert to their original positions. This issue affects approximately 60% of the global population, underscoring the importance of implementing effective measures to address orthodontic relapse. An approach in this regard involves the targeted administration of herbal and synthetic drugs applied directly to the specific area of interest to facilitate tooth movement and prevent orthodontic relapse. Apart from this, researchers are investigating the feasibility of utilizing different types of nanoparticles to improve the process of orthodontic tooth movement. In recent years, there has been a noticeable increase in the number of studies examining the effects of various drugs on orthodontics. However, the currently available literature does not provide significant evidence relating to orthodontic tooth movement. In this review, the authors provide valuable information about the drugs and nanomaterials that are capable of further enhancing the rate of orthodontic tooth movement and reducing the risk of orthodontic relapse. However, a notable hurdle remains, i.e., there is no marketed formulation available that can enhance orthodontic tooth movement and reduce treatment time. Therefore, researchers should try herbal-synthetic approaches to achieve a synergistic effect that can enhance orthodontic tooth movement. In this nutshell, there is an urgent need to develop a non-invasive, patient-compliant, and cost-effective formulation that will provide quality treatment and ultimately reduce the treatment time. Another critical issue is orthodontic relapse, which can be addressed by employing drugs that slow down osteoclastogenesis, thereby preventing tooth movement after treatment. Nevertheless, extensive research is still required to overcome this challenge in the future.

Marine-derived polysaccharides and their therapeutic potential in wound healing application - A review.

Polysaccharides originating from marine sources have been studied as potential material for use in wound dressings because of their desirable characteristics of biocompatibility, biodegradability, and low toxicity. Marine-derived polysaccharides used as wound dressing, provide several benefits such as promoting wound healing by providing a moist environment that facilitates cell migration and proliferation. They can also act as a barrier against external contaminants and provide a protective layer to prevent further damage to the wound. Research studies have shown that marine-derived polysaccharides can be used to develop different types of wound dressings such as hydrogels, films, and fibres. These dressings can be personalised to meet specific requirements based on the type and severity of the wound. For instance, hydrogels can be used for deep wounds to provide a moist environment, while films can be used for superficial wounds to provide a protective barrier. Additionally, these polysaccharides can be modified to improve their properties, such as enhancing their mechanical strength or increasing their ability to release bioactive molecules that can promote wound healing. Overall, marine-derived polysaccharides show great promise for developing effective and safe wound dressings for various wound types.

Nano-platform Strategies of Herbal Components for the management of Rheumatoid Arthritis: A Review on the Battle for Next-Generation Formulations.

INTRODUCTION: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that initially affects small joints and then spreads to the bigger joints. It also affects other organs of the body such as the lungs, eyes, kidneys, heart, and skin. In RA, there is destruction of cartilage and joints, and ligaments and tendons become brittle. Damage to the joints leads to abnormalities and bone degradation, which may be quite painful for the patient. METHOD: The nano-carriers such as liposomes, phytosomes, nanoparticles, microcapsules, and niosomes are developed to deliver the encapsulated phytoconstituents to targeted sites for the better management of RA. RESULTS: The phytoconstituents loaded nano-carriers have been used in order to increase bioavailability, stability and reduce the dose of an active compound. In one study, the curcumin-loaded phytosomes increase the bioavailability of curcumin and also provides relief from RA symptoms. The drug-loaded nano-carriers are the better option for the management of RA. CONCLUSION: In conclusion, there are many anti-arthritic herbal and synthetic medicine available in the market that are currently used in the treatment of RA. However, chronic use of these medications may result in a variety of side effects. Because therapy for RA is frequently necessary for the rest of ones life. The use of natural products may be a better option for RA management. These phytoconstituents, however, have several disadvantages, including limited bioavailability, low stability, and the need for a greater dosage. These problems can be rectified by using nano-technology.

Therapeutic Potential of Nanocarrier-Mediated Delivery of Phytoconstituents for Wound Healing: Their Current Status and Future Perspective.

The treatment of wounds is a serious problem all over the world and imposes a huge financial burden on each and every nation. For a long time, researchers have explored wound dressing that speeds up wound healing. Traditional wound dressing does not respond effectively to the wound-healing process as expected. Therapeutic active derived from plant extracts and extracted bioactive components have been employed in various regions of the globe since ancient times for the purpose of illness, prevention, and therapy. About 200 years ago, most medical treatments were based on herbal remedies. Especially in the West, the usage of herbal treatments began to wane in the 1960s as a result of the rise of allopathic medicine. In recent years, however, there has been a resurgence of interest in and demand for herbal medicines for a number of reasons, including claims about their efficacy, shifting consumer preferences toward natural medicines, high costs and negative side effects of modern medicines, and advancements in herbal medicines brought about by scientific research and technological innovation. The exploration of medicinal plants and their typical uses could potentially result in advanced pharmaceuticals that exhibit reduced adverse effects. This review aims to present an overview of the utilization of nanocarriers in plant-based therapeutics, including its current status, recent advancements, challenges, and future prospects. The objective is to equip researchers with a comprehensive understanding of the historical background, current state, and potential future developments in this emerging field. In light of this, the advantages of nanocarriers based delivery of natural wound healing treatments have been discussed, with a focus on nanofibers, nanoparticles, nano-emulsion, and nanogels.

Biocompatible phospholipid-based nanovesicular drug delivery system of ketoprofen: Systematic development, optimization, and preclinical evaluation.

The present work involved development of phospholipid-based permeation enhancing nanovesicles (PENVs) for topical delivery of ketoprofen. Screening of phospholipids and process parameters was performed. Central composite design was used for optimization of factors, that is, amount (%, w/w) of phospholipid and ethanol at three levels. The optimized nanovesicles (NVs) were loaded with different terpenes and then incorporated into a gel base. Optimized NVs exhibited 69% entrapment efficiency, 51% transmittance, 328 nm mean vesicle size, and polydispersity index of 0.25. In vitro release kinetics evaluation indicated best fitting as per Korsemeyer-Peppa's model and drug release via Fickian-diffusion mechanism. The optimized NVs loaded with mint terpene showed minimal degree of deformability and maximal elasticity as compared with the conventional NVs and liposomes. Rheology and texture analysis indicated pseudoplastic flow and smooth texture of the vesicle gel formulation. Ex vivo permeation studies across Wistar rat skin indicated low penetration (0.43-fold decrease) and high skin retention (4.26-fold increase) of ketoprofen from the optimized PENVs gel vis-à-vis the conventional gel. Skin irritancy study indicated lower scores for PENVs gel construing its biocompatible nature. Stability studies confirmed cold storage is best suitable for vesicle gel, and optimized PENVs were found to be suitable for topical delivery of ketoprofen.

Preservatives in Pharmaceuticals: Are They Really Safe?

Preservatives are the ingredients that are utilized in order to improve the shelf life of products (Medicines, food). These tend to slow down or stop the degradation or decomposition processes, therefore, enhance the shelf life of the products. These agents either interfere with the chemical reaction or check the growth of microorganisms in the products. Preservatives are classified according to the mode of action or source or chemical nature. The preservation efficacy can be affected by various factors, e.g., interaction with other components, nature of preservatives, type of containers, type of micro-organism, and pH. Despite being vital for various types of products, these chemicals are not safe, if not used appropriately. The review will provide an updated detail of different types of preservatives along with their safety aspect. This review also highlighted the maximum safe concentration of preservatives that can be required to develop a formulation with maximum safety and low toxicity.

Microbiome Medicine: Microbiota in Development and Management of Cardiovascular Diseases.

The gut microbiome consists of trillions of bacteria and other microbes whose metabolic activities and interactions with the immune system go beyond the gut itself. We are all aware that bacteria and other microorganisms have a significant impact on our health. Also, the health of the bacteria directly reflects the health status of the body where they reside. Eventually, alterations in the microbiome at different sites of a body are associated with many different diseases such as obesity, IBD, malnutrition, CVD, etc. Microbiota directly or indirectly affects the heart with the formation of plaques in the blood vessels, and cell walls become prone to lesion development. This ultimately leads to heightening the overall inflammatory status via increased bacterial translocation. Metabolites derived from the gut microbial metabolism of choline, phosphatidylcholine, and L-carnitine directly contribute to CVD pathology. These dietary nutrients have trimethylamine (TMA) moiety, which participates in the development of atherosclerotic heart disease. The objective of this review was to examine various metabolic pathways regulated by the gut microbiome that appear to alter heart function and lead to the development and progression of cardiovascular diseases, as well as how to target the gut microbiome for a healthier heart. In this review, we also discussed various clinical drugs having crosstalk between microbiota and heart and clinical trials for the gut-heart microbiome.

Plant based Bioavailability Enhancers.

Many of the synthetic and herbal drugs, despite their notable in vitro findings, demonstrate insignificant in vivo activity, the majority of the time due to poor bioavailability. As per Biopharmaceutical Classification System (BCS), one of the main concerns is low solubility and/or permeation of drugs resulting in reduced absorption and poor bioavailability. To overcome these issues, various strategies have been adopted, including the use of permeation enhancers which are also known as bioenhancers. Bioenhancers are synthetic or natural compounds that increase the bioavailability of drugs and nutrients such as vitamins, amino acids, minerals, etc., into the systemic circulation and at the site of action for exhibiting improved therapeutic action. By improving bioavailability, bioenhancers can reduce drug dose, decrease the treatment period, and circumvent the problem of drug resistance. Although numerous studies have reported the application of synthetic bioenhancers, plant based bioenhancers can serve as a better alternative owing to their natural origin. Literature reviews have revealed that plant-based bioenhancers have been used in a wide variety of antibiotics, antiviral, and anti-cancer therapeutics. These can be categorized based on their sources and mechanism of action. This review will provide a systematic and detailed overview of the various plant based bioenhancers and their applications.

Evaluation of efficacy and safety of a novel lipogel containing diclofenac: A randomized, placebo controlled, double-blind clinical trial in patients with signs and symptoms of osteoarthritis.

BACKGROUND: Effectiveness and safety of pharmaceuticals is the prime concern of every osteoarthritis (OA) treatment. Chronic administration of NSAIDs, especially in case of geriatrics, through oral route tend to compromise the patient's safety, whereas topical treatments are not found to be effective owing their poor ability to deliver drug molecules.Thus, the present study deals with a randomized, double-blind, controlled trial conducted on patients with knee osteoarthritis (OA) for comparing the performance of a novel topical gel (liposomal gel) of diclofenac with a placebo and a marketed gel. METHODS: The patients were treated and evaluated for 6 weeks as per the Western Ontario McMaster Universities (WOMAC) Index for OA. Patients were also observed for any adverse events. All the results were analyzed statistically using Kruskal-Wallis test, followed by Student's t-test at p ≤ 0.05. RESULTS: Patients treated with liposomal gel showed statistically significantly improvements in treatment in comparison to the other tested formulations. All the treatments were found to be well tolerated with no report of adverse event. The results unequivocally demonstrated the superiority of the diclofenac liposomal gel, in the relieving the symptoms of OA of the knee, in comparison to placebo and marketed gel. CONCLUSION: From above results it was revealed that the drug in liposome have higher therapeutic potential. Thus, this can be a safe and effective option for the management of chronic OA especially for geriatric patients.

Exploring the possibilities of capacitively coupled contactless conductivity detection in combination with liquid chromatography for the analysis of polar compounds using aminoglycosides as test case.

The analysis of highly polar (often charged) compounds which lack a strong UV absorbing chromophore is really challenging. Despite the numerous analytical methods published, the demand for a simple, robust and cheap technique for their analysis still persists. Here, reversed phase (RP) liquid chromatography (LC) with capacitively coupled contactless conductivity detection (C(4)D) was explored for the first time as a possible method for separation and detection of various aminoglycoside (AMG) antibiotics which were taken as typical test compounds: tobramycin (TOB), spectinomycin, streptomycin, amikacin, kanamycin A and kanamycin B. C(4)D was performed using a commercially available as well as a laboratory made cell. As ion-pairing reagents (IPR) four perfluorinated carboxylic acids were used: pentafluoropropionic acid, heptafluorobutyric acid, nonafluoropentanoic acid (NFPA) and pentadecafluorooctanoic acid (PDFOA). 0.125 mM NFPA-acetonitrile (ACN) (90:10) or 0.125 mM PDFOA-ACN (70:30) as mobile phases were suitable to detect TOB with reasonable retention times. However, NFPA was preferred for practical reasons. Its applicable concentration range in the mobile phase was strongly restricted by loss of chromatographic performance at lower levels and excessive background conductivity at higher levels. Overall repeatability and robustness of the method were rather poor which was explained by the relatively low IPR levels. Selectivity between the tested AMGs was mainly influenced by the number of protonated amino groups per molecule making it impossible to separate compounds of equal net charges. Problems encountered with gradient elution, hydrophilic interaction liquid chromatography (HILIC) and separation at high pH without IPRs are also discussed.

Development and validation of an indirect pulsed electrochemical detection method for monitoring the inhibition of Abl1 tyrosine kinase.

A new method for monitoring the enzyme inhibition of Abl1 tyrosine kinase by liquid chromatography-indirect pulsed electrochemical detection (LC-InPED) was developed. In this method, adsorption of a peptide analyte at the noble metal electrode suppresses the oxidation of polyols under alkaline condition to elicit an indirect response resulting in a negative peak of the target peptide. Among the reagents tested, D-gluconic acid sodium salt gave the best overall signal to noise (S/N) values for the indirect detection of p-Abltide, the product of Abl1 enzymatic reaction. 50 µM D-gluconic acid sodium salt dissolved in a mixture of 78% water-22% acetonitrile-0.03% trifluoroacetic acid (TFA) was used as the mobile phase. Chromatographic separation was achieved on an Alltima C18 (I.D. 5 µm; 250 mm × 4.6 mm) column with the mobile phase flow rate of 0.5 ml/min. 0.5M sodium hydroxide was added post-column to maintain alkaline conditions in the PED cell. The limit of quantification (LOQ) was 0.2 µM for p-Abltide, which was about 50-fold lower than direct PED analysis. The residual plot of the linear calibration curve indicated a good fit with a linear model within the investigated concentration range of p-Abltide. Intra- and inter-day precision was not more than 6.5% and accuracy was from -5.75% to +1.54%. The validated LC-InPED method was successfully applied for monitoring of p-Abltide in Abl1 enzyme reaction and the inhibition study of Abl1. The determined IC50 values of model inhibitors, imatinib, nilotinib and dasatinib, were 601.4 nM (R(2)=0.99), 32.3 nM (R(2)=0.99) and 1.3 nM (R(2)=0.98), respectively. These results were consistent with literature data. To the best of our knowledge this is the first time a LC-InPED method has been used to monitor an enzyme reaction.

Premenstrual syndrome, body fat and bitter taste receptor gene TAS2R38 among adult Kullu females of Himachal Pradesh, India.

OBJECTIVE: Premenstrual syndrome (PMS) is still a poorly understood and accepted condition. We evaluate the phenotypic variations at TAS2R38 gene locus in relation to PMS severity and adiposity measures among adult women. This is the first ever report describing association of PTC taste genetic locus with the PMS susceptibility. METHODS: The study was based on a cross-sectional sample of 105 adult rural women from the Kullu district, Himachal Pradesh. Retrospective approach was used to assess PMS. PTC tasting ability was assessed after Harris & Kalmus (1949). Each subject was measured for height, weight and body fat measures. RESULTS: 19.05% of the females were PTC non-tasters and 80.95% were tasters. Prevalence of PMS was 45.71%. Prevalence of severe type of PMS was very low, varying from 0-6%. Severity was highest in PMS-A type characterized by anxiety/irritability, tension, clumsiness, mood swings, nervousness, and insomnia. Females who tasted PTC bitter at lower concentrations had lowest PMS prevalence, while those who tasted PTC at higher concentration had highest PMS prevalence. Stature and body weight decreased with increase in PTC taste sensitivity. However, one-way ANOVA revealed that all the F-ratios were insignificant between the three discrete categories of low, medium and high PTC thresholds. CONCLUSION: Our results are compatible with the hypothesis that the bitter receptor gene TAS2R38 could not serve as a significant predictor of anthropometric measurements though some indirect pathways may not be ruled out, but the gene is significantly correlated with PMS susceptibility and severity.

Analysis of micronomicin by liquid chromatography with pulsed electrochemical detection.

This paper describes the separation of the main component micronomicin from its related substances using a new established liquid chromatographic method with pulsed electrochemical detection (LC-PED). The mobile phase consists of 1 volume of acetonitrile and 99 volumes of an aqueous solution containing 1.25% (v/v) trifluoroacetic acid, 0.025% (v/v) pentafluoropropionic acid and 0.85% (v/v) of 50% sodium hydroxide. The pH of the aqueous solution is adjusted to 2.6 with 0.5 M NaOH. The influence of the different chromatographic parameters on the separation was investigated. A quadruple-potential waveform was used as detection waveform. 0.5 M NaOH was added post column at a flow rate of 0.3 mL/min to raise the pH of detection to at least 12. The LOD and LOQ of micronomicin are 0.08 µg/mL (1.6 ng injected) and 0.25 µg/mL (5 ng injected), respectively. The linearity of micronomicin ranges from 0.25 to 60 µg/mL with a correlation coefficient of 0.9978. Intra-day RSD and inter-day RSD of micronomicin are 0.89% and 0.55%, respectively. This method proved to be robust and is also applicable to a wider number of C18 columns. A number of commercial samples of micronomicin sulfate were analyzed using this method and 18 peaks can be separated from the main component and from each other in one sample. Seven peaks could be identified using reference substances. The chemical structure of two unknown impurities could be characterized by LC-MS based on comparison of their fragmentation patterns with those of available reference substances.

Characterization of impurities in tylosin using dual liquid chromatography combined with ion trap mass spectrometry.

Investigation of unknown impurities in a tylosin sample was performed using liquid chromatography coupled to mass spectrometry (LC/MS). Separation was performed according to the recently described LC-UV method of Ashenafi et al. (2011) [14]. This method was reported to have a good selectivity as it was able to separate the four main components of tylosin from the already known and 23 unknown impurities. However, as this method uses a mobile phase with non-volatile constituents, direct characterization of these impurities using LC/MS was not possible. The impurity fractions were therefore first collected and then desalted before sending them to the MS. Identification of the impurities in the tylosin sample was performed with a quadruple ion trap (IT) MS, with an electrospray ionization (ESI) source in the positive ion mode. The structure of the impurities was deduced by comparing their fragmentation pattern with those of the main components of tylosin. As several peaks in the LC-UV method contained multiple compounds, using this method in total 41 new impurities were (partly) characterized.