Exploring Innovative Approaches in Type-2 Diabetes Management: A Comprehensive Review on Nano-carriers and Transdermal Drug Delivery.

Diabetes is a chronic metabolic disorder characterized by elevated blood sugar levels and encompasses various types like type 1, type 2, gestational, and prediabetes. This review delves into the intricacies of type-2 diabetes mellitus and its ideal management. Presently, a spectrum of herbal and synthetic drugs is employed for type-2 diabetes mellitus management. We gathered information about diabetes mellitus from articles published up to 2024 and listed in PubMed, Web of Science, Elsevier, Google Scholar, and similar databases. The keywords used in our search included "diabetes", "herbal drugs", "nano-carriers", "transdermal drug delivery", etc. By carefully analyzing the research on type-2 diabetes-mellitus, it was found that there is an increase in diabetes-based research, which can be demonstrated by contemplating the PubMed search engine results using transdermal delivery for type-2 diabetes-mellitus as a keyword. The oral consumption of these drugs is associated with numerous side effects, including obesity, pancreatic cancer, and hormonal imbalances. To surmount these challenges, the utilization of nano-carriers and transdermal drug delivery systems emerges as a promising avenue aiming to enhance the therapeutic efficacy of drugs. Nano-carriers represent a revolutionary approach, integrating cutting-edge technologies, inventive strategies, and methodologies to deliver active molecules in concentrations that are both safe and effective, thereby eliciting the desired pharmacological response. This review critically examines the constraints associated with traditional oral administration of anti-diabetic drugs and underscores the manifold initiatives undertaken to revolutionize drug delivery. This review focuses on the limitations associated with the conventional oral administration of anti-diabetic drugs and the many initiatives made so far for the effective and safe delivery of drugs using innovative constituents and techniques.

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.

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.

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.

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.

Identification of impurities in polymyxin B and colistin bulk sample using liquid chromatography coupled to mass spectrometry.

The European Pharmacopoeia (Ph. Eur.) describes liquid chromatography-ultraviolet (LC-UV) methods using C(18) stationary phases for the analysis of polymyxin B and colistin. Several unknown impurities were detected in commercial samples of those polypeptide complexes. However, the Ph. Eur. does not specify any related substances for polymyxin B and colistin. Since both methods use non-volatile buffers, the mobile phases were incompatible with mass spectrometry (MS). For the identification of related substances in bulk samples by LC/MS, volatile mobile phase systems were developed. However, the LC/MS methods (with volatile additives) showed inferior chromatographic separation compared to the LC-UV method (with non-volatile additives). Moreover, previously identified impurities by LC/MS could not be assigned in LC-UV methods as the separation in both systems was different. In this study, known impurities were traced in the LC-UV methods and new impurities present in polymyxin B and colistin bulk samples were characterized. To achieve this, each peak from the non-volatile system was collected separately and reinjected into an LC system with a volatile mobile phase coupled to MS. This way, collected impurity peaks were rechromatographed on a reversed phase column in order to separate the analyte from the buffer salts. Using this method, out of 39 peaks, five novel related substances were characterized in a polymyxin B bulk sample. Fourteen impurities, which were already reported in the literature were traced as good as possible in the LC-UV method. In the case of colistin, a total of 36 peaks were investigated, among which four new compounds. Additionally, 30 known impurities were traced in the LC-UV method.

Potential prospects of chitosan derivative trimethyl chitosan chloride (TMC) as a polymeric absorption enhancer: synthesis, characterization and applications.

In recent years, researchers have been working extensively on various novel properties of polymers to develop increased efficiency of drug delivery and improve bioavailability of various drug molecules, especially macromolecules. Chitosan, a naturally occurring polysaccharide, because of its protonated/polymeric nature, provides effective and safe absorption of peptide and protein drugs. Its transmucosal absorption is, however, limited to acidic media because of its strong intermolecular hydrogen bonds. A new partially quaternized chitosan derivative, N-trimethyl chitosan chloride (TMC), has been synthesized with improved solubility, safety and effectiveness as an absorption enhancer at neutral pH and in aqueous environment. It enhances the absorption, especially of peptide drugs, by reversible opening of tight junctions in between epithelial cells, thereby facilitating the paracellular diffusion of peptide drugs. This derivative thus opens new perspectives as a biomaterial for various pharmaceutical applications/drug delivery systems. This review deals with the potential use of the quaternized chitosan derivative as a permeation enhancer for the mucosal delivery of macromolecular drugs along with its other biomedical applications.