Hesperidin-loaded cubogel as a novel therapeutic armamentarium for full-thickness wound healing.

Wounds are a physical manifestation of injury to the skin causing it to rupture or tear. The process of wound healing naturally restores skin integrity while minimizing the extent of the damage. Hesperidin (HPN) is a natural polyphenolic flavonoid and is effective in treating wounds due to its ability to reduce inflammation and stimulate angiogenesis. However, its use is limited by its poor physicochemical attributes such as poor solubility in water. Recently, nanoparticles, particularly Cubosomes, are found to be promising candidates for advancing wound-healing therapies, owing to their unique properties. The present study was conducted to develop a hydrogel system based on Cubosomes encapsulating HPN (HPN-Cubogel), with the potential to mitigate full-thickness wounds. The therapeutic efficacy of the formulation assessed in the animal model showed that the HPN-Cubogel formulation group exhibited a wound closure rate of 98.96 ± 1.50% after 14 days post-wounding compared to 89.12 ± 2.6% in the control group suggesting superior wound contraction activity. Collagen synthesis was superior in the formulation compared to the control group, as determined through MT staining. In summary, the HPN-Cubogel formulation was found to be the most effective in enhancing full-thickness wound healing.

siRNA therapeutics: insights, challenges, remedies and future prospects.

INTRODUCTION: Among conventional and novel therapeutic approaches, the siRNA strategy stands out for treating disease by silencing the gene responsible for the corresponding disorder. Gene silencing is supposedly intended to target any disease-causing gene, and therefore, several attempts and investments were made to exploit siRNA gene therapy and advance it into clinical settings. Despite the remarkable beneficial prospects, the applicability of siRNA therapeutics is very challenging due to various pathophysiological barriers that hamper its target reach, which is the cytosol, and execution of gene silencing action. AREAS COVERED: The present review provides insights into the field of siRNA therapeutics, significant in vivo hurdles that mitigate the target accessibility of siRNA, and remedies to overcome these siRNA delivery challenges. Nonetheless, the current review also highlights the on-going clinical trials and the regulatory aspects of siRNA modalities. EXPERT OPINION: The siRNAs have the potential to reach previously untreated target sites and silence the concerned gene owing to their modification as polymeric or lipidic nanoparticles, conjugates, and the application of advanced drug delivery strategies. With such mounting research attempts to improve the delivery of siRNA to target tissue, we might shortly witness revolutionary therapeutic outcomes, new approvals, and clinical implications.

Silver-dendrimer nanocomposite as emerging therapeutics in anti-bacteria and beyond.

To develop next-generation nanomedicine, theranostic nanotherapeutic strategies are increasingly being emphasized. In recent years, it is observed that the effective lifetime of anti-bacterial and anti-cancer agent is diminishing, which undermines the economic incentives necessary for clinical development and therapeutic applications. Thus, novel formulations ought to not only kill drug resistant strains and cancerous cells but also inhibit their formation. Recently, metallic nanoparticles [for example- silver (Ag) nanoparticles] have been widely investigated for their biomedical applications. The so-called applications necessitate the inclusion of these nanoparticles inside polymeric matrices (for example- dendrimer) leading to chemical functionalization of the metallic nanoparticles. Silver and silver nanoparticles' antibacterial activity has already been well established over years. Dendrimers due to their homogeneous highly branched structure and uniform composition are perfectly suitable for the inclusion of silver nanoparticles [Ag NPs]. Recently, the increasing trend in the development of Ag-dendrimer nanocomposites is attributed to the excellent antibacterial activity of Ag as well as dendrimer's unique properties like variable functional terminal ends and potential antibacterial effect necessarily. This review provides an informative overview regarding the numerous aspects of bactericidal and other biomedical applications of Ag-dendrimer nanocomposites, particularly emphasizing analysis of existing research and prospective worth to the pharmaceutical sector in future.

Unravelling the enigma of siRNA and aptamer mediated therapies against pancreatic cancer.

Pancreatic cancer (PC) is a fatal disease that has a poor 5-year survival rate. The poor prognosis can be attributed to both troublesome detections at the initial stage, which makes the majority of the treatment options largely unsuccessful and leads to extensive metastasis, as well as to its distinct pathophysiological characteristics, such as rich desmoplastic tumours bounded by dysplastic and hypo perfused vessels restricting the mobility of therapeutic agents. Continued attempts have been made to utilise innovative measures for battling PC to increase the therapeutic effectiveness of therapies and overcome their cytotoxicity. Combined cancer targeting and gene silencing approach has shown improved outcomes in patients' survival rates and quality of life, offering a potential solution to therapeutic complications. It particularly targets various barriers to alleviate delivery problems and diminish tumour recurrence and metastasis. While aptamers, a type of single-stranded nucleic acids with strong binding affinity and specificity to target molecules, have recently surfaced as a viable PC strategy, siRNA can interfere with the expression of certain genes. By concurrently suppressing genes and boosting targeted approach, the cocktail of siRNA/Aptamer and other therapeutic drugs can circumvent the multi-drug resistance phenomena. Additionally, combination therapy with additive or synergistic effects can considerably increase the therapeutic efficacy of anti-cancer medications. This study outlines the primary difficulties in treating PC, along with recent developments in siRNA/Aptamer mediated drug delivery to solve the major hiccup of oncology field.

Lipid-based nanocarrier mediated CRISPR/Cas9 delivery for cancer therapy.

CRISPR/Cas mediated gene-editing has opened new avenues for therapies that show great potential for treating or curing cancers, genetic disorders, and microbial infections such as HIV. CRISPR/Cas9 tool is highly efficacious in revolutionizing the advent of genome editing; however, its efficient and safe delivery is a major hurdle due to its cellular impermeability and instability. Nano vectors could be explored to scale up the safe and effective delivery of CRISPR/Cas9. This review highlights the importance of CRISPR/Cas9 genome editing system in cancer treatment along with the effect of lipid-based nanoparticles in its safe delivery to cancer cells. The solid-lipid nanoparticles, nanostructured lipid carrier, lipid nanoparticles and niosomes have shown great effect in the delivery of CRISPR compounds to the cancer cells. The design and genome editing application in cancer therapy has been discussed along with the future concern and prospects of lipid nanoparticle based CRISPR/Cas9 has been focused toward the end.

Polymeric nanoparticles-siRNA as an emerging nano-polyplexes against ovarian cancer.

Ovarian cancer (OC) is considered fifth-deadliest cancer globally responsible for high mortality in women. As the conventional therapeutic and diagnostic approaches are ineffective in increasing the survival rates of advanced staged patients by more than 5 years, OC has resulted in high morbidity and mortality rates over the last two decades. As a result, there is a dire need for innovative treatment approaches to address the issues. RNAi and nanotechnology can be considered the most appropriate strategies that can be used to improve OC therapy and help circumvent the chemo-resistance. siRNA is considered highly successful in facilitating the knockdown of specific genes on entering the cytosol when administered in-vivo via inhibiting the mRNA expression responsible for translation of those specific genes through the mechanism called RNA interference (RNAi). However, the primary barrier of utmost importance in the clinical efficacy of employed siRNA for the treatment of OC is the systemic distribution to the targeted site from the administration site. As a result, nanoparticles are constructed to carry the siRNA molecules inside them to the targeted site by preventing serum degradation and enhancing the serum stability of administered siRNA. The present review assesses the developments made in the polymeric-based nanoparticle siRNA delivery for targeting particular genes involved in the prognosis of ovarian cancers and surpassing the chemo-resistance and thus improving the therapeutic potentials of administered agents.