Unlocking the role of herbal cosmeceutical in anti-ageing and skin ageing associated diseases.

The process of skin ageing is a natural biological phenomenon characterised by the emergence of wrinkles, age spots, sagging skin, and dryness over time. The increasing significance of skin in physical attractiveness has heightened skincare concerns. Anti-ageing cosmetics play a pivotal role in nurturing the skin, enhancing its quality, and promoting overall health. Today, cosmetics have evolved beyond mere aesthetics and are now integral to individual wellness. The contemporary quest for perpetual youth has intensified, prompting a deeper exploration into the skin ageing process. This comprehensive exploration delves into various elements involved in skin ageing, encompassing cells such as stem and endothelial cells, blood vessels, soft tissues, and signalling pathways. The molecular basis of skin ageing, including biochemical factors like reactive oxygen species, damaged DNA, free radicals, ions, and proteins (mRNA), is scrutinised alongside relevant animal models. The article critically analyzes the outcomes of utilising herbal components, emphasising their advantageous anti-ageing properties. The factors contributing to skin ageing, mechanistic perspectives, management approaches involving herbal cosmeceutical, and associated complications (especially cardiovascular diseases, Parkinson's, Alzheimer's, etc.) are succinctly addressed. In addition, the manuscript further summarises the recent patented innovations and toxicity of the herbal cosmeceuticals for anti-ageing and ageing associated disorders. Despite progress, further research is imperative to unlock the full potential of herbal components as anti-ageing agents.

Exploring Nanocarriers as Treatment Modalities for Skin Cancer.

Cancer is a progressive disease of multi-factorial origin that has risen worldwide, probably due to changes in lifestyle, food intake, and environmental changes as some of the reasons. Skin cancer can be classified into melanomas from melanocytes and nonmelanoma skin cancer (NMSC) from the epidermally-derived cell. Together it constitutes about 95% of skin cancer. Basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (CSCC) are creditworthy of 99% of NMSC due to the limited accessibility of conventional formulations in skin cancer cells of having multiple obstacles in treatment reply to this therapeutic regime. Despite this, it often encounters erratic bioavailability and absorption to the target. Nanoparticles developed through nanotechnology platforms could be the better topical skin cancer therapy option. To improve the topical delivery, the nano-sized delivery system is appropriate as it fuses with the cutaneous layer and fluidized membrane; thus, the deeper penetration of therapeutics could be possible to reach the target spot. This review briefly outlooks the various nanoparticle preparations, i.e., liposomes, niosomes, ethosomes, transferosomes, transethosomes, nanoemulsions, and nanoparticles technologies tested into skin cancer and impede their progress tend to concentrate in the skin layers. Nanocarriers have proved that they can considerably boost medication bioavailability, lowering the frequency of dosage and reducing the toxicity associated with high doses of the medication.

Nisin and nisin-loaded nanoparticles: a cytotoxicity investigation.

OBJECTIVE: Nisin is an antibacterial peptide with anticancer properties, but the main drawback is its rapid enzymatic degradation and limited permeation across the cell membrane. This research aims to overcome these drawbacks by developing nisin-loaded nanoparticles (NPN) with improved cytotoxic effects. SIGNIFICANCE: PLGA nanoparticles are one of the most effective biodegradable and biocompatible drug delivery carriers. In the present study, nisin-loaded nanoparticles showed enhanced anticancer effects. METHODS: NPN was prepared by a double emulsion solvent evaporation method and characterized for different parameters. The cytotoxic investigation of NPN was carried out on various cell lines, including A549, SW-620, HT-29, PC-3, MDA-MB-231, MCF-7, MiaPaca-2, and fR2 by sulforhodamine B (SRB) assay. Mechanistic investigation of cellular cytotoxicity was performed by using bright-field microscopy, DAPI staining, intracellular reactive oxygen species (ROS), changes in mitochondrial membrane potential (ΔΨm), Western blotting and cellular uptake study. A comparative cytotoxicity study of nisin and NPN was performed on normal breast epithelial cells (fR2). RESULTS: NPN showed spherical shape, 289.09 ± 3.63 nm particle size, and 63.37 ± 3.12% entrapment efficiency. NPN was more cytotoxic to the MDA-MB-231 cell line, showing higher nuclear fragmentation, ROS generation, depletion of ΔΨm, and enhanced intracellular uptake with apoptosis signs compared with nisin and with no cytotoxicity on normal cells. CONCLUSIONS: The findings suggest that nisin delivery via PLGA nanoparticles can be used to treat cancer without significant effects on healthy cells.

Carbopol-olive oil-based bigel drug delivery system of doxycycline hyclate for the treatment of acne.

OBJECTIVE: The objective of this study was to prepare and evaluate the doxycycline hyclate containing bigel for the effective treatment of acne. METHODS: Bigels are biphasic systems formed by water-based hydrogels and oil-based organogel. Carbopol 940 was used to prepare the hydrogel phase, whereas Span-60 and olive oil for the oleogel phase. RESULTS: The microstructure of bigel confirmed the oil in water type emulsion formation. The average droplet size of formulations was found 15-50 µm, and a bell-shaped droplet distribution curve, rheological, or viscosity studies suggested that the consistency and stability of bigel decrease with high organogel concentration. Three formulations (F1, F2, and F3) of the different ratios of hydrogel:oleogel (60:40, 70:30, and 80:20) were prepared in which F1 was less stable compared to F2 and F3. The drug content of F2 and F3 was respectively 79.94 and 71.33%. Formulation F2 was found more effective as compared to F3 based on in vitro drug release studies. Bigel also showed better results during in vivo studies at the rabbit ear model, which reduce acne diameter up to 1.10 mm from 4.9 mm while gel reduced it up to 1.20 mm.

Lectin-Conjugated Clarithromycin and Acetohydroxamic Acid-Loaded PLGA Nanoparticles: a Novel Approach for Effective Treatment of H. pylori.

Helicobacter pylori infection remains challenging as it mainly colonized beneath the deep gastric mucosa and adheres to epithelial cells of the stomach. Concanavalin-A (Con-A)-conjugated gastro-retentive poly (lactic-co-glycolic acid) (PLGA) nanoparticles of acetohydroxamic acid (AHA) and clarithromycin (CLR) were prepared and evaluated under in vitro conditions. Solvent evaporation method was employed for preparation of nanoparticles and characterized for particle size distribution, surface morphology, percent drug entrapment, and in vitro drug release in simulated gastric fluid. Optimized nanoparticles were conjugated with Con-A and further characterized for Con-A conjugation efficiency and mucoadhesion and tested for in vitro anti-H. pylori activity. The conjugation with Con-A further sustained the drug release over a period of 8 h when compared to non-conjugated nanoparticles of AHA and CLR. In vitro anti H. pylori study confirmed that Con-A-conjugated nanoparticles containing both drugs, i.e., CLR and AHA, had shown maximum zone of inhibition compared to other formulations. In a nut shell, results suggest that the developed systems could be used for better therapeutic activity against H. pylori infection.

Cationic nanocarriers: A potential approach for targeting negatively charged cancer cell.

Cancer, a widespread and lethal disease, necessitates precise therapeutic interventions to mitigate its devastating impact. While conventional chemotherapy remains a cornerstone of cancer treatment, its lack of specificity towards cancer cells results in collateral damage to healthy tissues, leading to adverse effects. Thus, the quest for targeted strategies has emerged as a critical focus in cancer research. This review explores the development of innovative targeting methods utilizing novel drug delivery systems tailored to recognize and effectively engage cancer cells. Cancer cells exhibit morphological and metabolic traits, including irregular morphology, unchecked proliferation, metabolic shifts, genetic instability, and a higher negative charge, which serve as effective targeting cues. Central to these strategies is the exploitation of the unique negative charge characteristic of cancer cells, attributed to alterations in phospholipid composition and the Warburg effect. Leveraging this distinct feature, researchers have devised cationic carrier systems capable of enhancing the specificity of therapeutic agents towards cancer cells. The review delineates the underlying causes of the negative charge in cancer cells and elucidates various targeting approaches employing cationic compounds for drug delivery systems. Furthermore, it delves into the methods employed for the preparation of these systems. Beyond cancer treatment, the review also underscores the multifaceted applications of cationic carrier systems, encompassing protein and peptide delivery, imaging, photodynamic therapy, gene delivery, and antimicrobial applications. This comprehensive exploration underscores the potential of cationic carrier systems as versatile tools in the fight against cancer and beyond.

Inulin: Unveiling its potential as a multifaceted biopolymer in prebiotics, drug delivery, and therapeutics.

In recent years, inulin has gained much attention as a promising multifunctional natural biopolymer with numerous applications in drug delivery, prebiotics, and therapeutics. It reveals a multifaceted biopolymer with transformative implications by elucidating the intricate interplay between inulin and the host, microbiome, and therapeutic agents. Their flexible structure, exceptional targetability, biocompatibility, inherent ability to control release behavior, tunable degradation kinetics, and protective ability make them outstanding carriers in healthcare and biomedicine. USFDA has approved Inulin as a nutritional dietary supplement for infants. The possible applications of inulin in biomedicine research inspired by nature are presented. The therapeutic potential of inulin goes beyond its role in prebiotics and drug delivery. Recently, significant research efforts have been made towards inulin's anti-inflammatory, antioxidant, and immunomodulatory properties for their potential applications in treating various chronic diseases. Moreover, its ability to reduce inflammation and modulate immune responses opens new avenues for treating conditions such as autoimmune disorders and gastrointestinal ailments. This review will attempt to illustrate the inulin's numerous and interconnected roles, shedding light on its critical contributions to the advancement of healthcare and biomedicine and its recent advancement in therapeutics, and conclude by taking valuable insights into the prospects and opportunities of inulin.

Blockchain technology: A potential tool for the management of pharma supply chain.

BACKGROUND: The pharma supply chain comprises various parties including distributors, manufacturers, raw material suppliers, regulators, pharmacies, hospitals, and patients. Due to the product's complexity and transaction flows, an efficient traceability system is needed in the pharma supply chain to identify the current and all previous product owners. Digitizing the track and trace process significantly improves regulatory oversight and guarantees product quality. A distributed platform for shared data that is immutable, trustworthy, accountable, and transparent in the pharmaceutical supply chain could be built using blockchain-based drug traceability. OBJECTIVE: This review aims to shed light on blockchain technology's significance and necessity for pharmaceutical supply chain management systems. METHOD: A comprehensive literature review was performed between January 2017 and September 2023. The search was conducted to elaborate on blockchain technology. Blockchain is a software-based technology that logs and records transactions using a block structure arranged chronologically. Cryptography technology links and secures these blocks on a peer-to-peer network. Blockchain is anticipated to transform the pharmaceutical supply chain by giving all participants access to a single, straightforward system that provides transparency, security, and oversight of the end-to-end delivery of goods. RESULT: In all, various literature data were included in this review. Using a supply chain powered by blockchain has many benefits. To begin with, it gives a thorough account of the entire procedure from start to finish. A single piece of software can manage the entire supply chain. Additionally, it increases communication between parties with permission. The enhanced security and traceability that blockchain offers is another important benefit. A blockchain system can track, trace, and recall products. CONCLUSION: Blockchain-based pharmaceutical supply chain management enables the tracking of medicinal drug transactions from raw materials suppliers to end consumers. The pharma blockchain has the potential to enhance the security, integrity, data provenance, and functionality of the supply chain due to its transparency, immutability, and auditability.

Transethosomes: A Promising Challenge for Topical Delivery Short Title: Transethosomes for Topical Delivery.

Skin provides an excellent barrier to molecular transport, as the stratum corneum is the most formidable barrier to the passage of most pharmaceuticals. Various attempts have been made to improve drug administration into the body through intact skin. Though very few routes are as attractive as the topical route, drug transport through the skin is challenging. To overcome the challenges, researchers have found a system in which the drug is encapsulated into the vesicle, penetrating deeper into the skin to hit the target site. Vesicular systems like transethosome, an ultra- deformable vesicle (UDV), tend to accumulate in the skin layers. Since transethosomes have small particle size and can easily alter the shape of vesicles compared to other vesicular systems, they can penetrate through the layers of skin. Hence, the drug encapsulated into transethosomes can easily reach the target site. Transethosomes consist of ethanol and phospholipids along with an edge activator. Ethanol and edge activator help to enhance the skin permeation of transethosomes. Various methods of preparation of transethosomes, comparison of transethosomes with other lipid vesicles, characterization of transethosomes, and application of transethosomes have been covered in this review. Transethosomes can deliver a different variety of drugs, such as anticancer, corticosteroids, proteins and peptides, analgesics.

Development and optimization of transethosomal gel of apigenin for topical delivery: In-vitro, ex-vivo and cell line assessment.

The main aim of this study was to optimize the transethosomes of apigenin formulated by the thin film hydration method using surfactant Span 80. Response surface Box-Behnken design with three levels of three factors was used to design and optimize the formulations. The prepared transethosomal formulations were characterized for entrapment efficiency, vesicle size, and flux to obtain the optimized formulation batch. The optimized batch was further incorporated into the gel and characterized for the in-vitro, ex-vivo, and cytotoxic studies. The result showed the optimized transethosomes were smooth, nanosized, unilamellar, and spherical with an entrapment efficiency of 78.75 ± 3.14 %, a vesicle size of 108.75 ± 2.31 nm, and a flux of 4.10 ± 0.63 µg/cm2/h. In-vitro cumulative drug release of transethosomal gel of apigenin (TEL gel) and the conventional gel was 92.25 ± 3.5 % and 53.40 ± 3.10 %, respectively, after 24 h study. Ex-vivo permeation of TEL gel and conventional gel showed 86.20 ± 3.60 % and 51.20 ± 3.20 % permeation of apigenin at 24 h, respectively. A cytotoxic study confirmed that TEL gel significantly reduces cell viability compared to conventional gel. The results suggested that topical application of apigenin transethosomal gel may be a better treatment strategy for skin cancer because of the prolonged sustained release of the drug and the better permeability of apigenin through the skin.

Design and Evaluation of SLNs Encapsulated Curcumin-based Topical Formulation for the Management of Cervical Cancer.

OBJECTIVE: Curcumin has the propensity to inhibit cancer growth, slow cancer development, increase chemotherapy effectiveness, and shield healthy cells from radiation treatment harm. As a result of curcumin's ability to block several signaling pathways, cervical cancer cells can once again proliferate normally. To optimize topically applied curcumin-loaded solid lipid nanoparticles (SLNPs) for the treatment of cervical cancer, this study set out to establish the relationship between design variables and experimental data. It also performed in vitro characterizations to determine the formulation's efficacy and safety. METHODS: Curcumin-loaded SLNPs were constructed and optimized using a systematic design of experiment (DoE) technique. SLNPs that were loaded with curcumin were produced utilizing a cold emulsification ultrasonication process. Using the Box Behnken Design, it was determined how independent variables (factors) like the quantity of lipid (A), the quantity of phospholipid (B), and the concentration of surfactant (C) affected the responses of the dependent variables (responses), such as particle size (Y1), polydispersity index (PDI) (Y2), and entrapment efficiency (EE) (Y3) (BBD). RESULTS: The ideal formulation (SLN9) was chosen using the desirability technique based on 3-D surface response graphs. Using polynomial equations and three-dimensional surface plots, the influence of independent factors on the dependent variables was evaluated. The observed responses were almost equal to the levels that the optimal formulation expected. The improved SLNP gel's shape and other physicochemical characteristics were also assessed, and they were determined to be ideal. The sustained release profile of the produced formulations was validated by in vitro release tests. Studies on hemolysis, immunogenic response, and in vitro cell cytotoxicity demonstrate the efficacy and safety of the formulations. CONCLUSION: To improve the treatment effect, chitosan-coated SLNPs may carry encapsulated curcumin to the desired location and facilitate its localization and deposition in the desired vaginal tissue.

Critical parameters for design and development of multivalent nanoconstructs: recent trends.

A century ago, the groundbreaking concept of the magic bullet was given by Paul Ehrlich. Since then, this concept has been extensively explored in various forms to date. The concept of multivalency is among such advancements of the magic bullet concept. Biologically, the concept of multivalency plays a critical role in significantly huge numbers of biochemical interactions. This concept is the sole reason behind the higher affinity of biological molecules like viruses to more selectively target the host cell surface receptors. Multivalent nanoconstructs are a promising approach for drug delivery by the active targeting principle. Designing and developing effective and target-specific multivalent drug delivery nanoconstructs, on the other hand, remain a challenge. The underlying reason for this is a lack of understanding of the crucial interactions between ligands and cell surface receptors, as well as the design of nanoconstructs. This review highlights the need for a better theoretical understanding of the multivalent effect of what happens to the receptor-ligand complex after it has been established. Furthermore, the critical parameters for designing and developing robust multivalent systems have been emphasized. We have also discussed current advances in the design and development of multivalent nanoconstructs for drug delivery. We believe that a thorough knowledge of theoretical concepts and experimental methodologies may transform a brilliant idea into clinical translation.

COVID-19 Infection: Targeting Possibilities for Treatment.

The outbreak of novel coronavirus (nCoV) or severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in December 2019 in Wuhan, China, has posed an international public health emergency worldwide and forced people to be confined in their homes. This virus is of high-risk category and is declared a pandemic by the World Health Organization (WHO). The worldwide researchers and various health professionals are working together to determine the best way to stop its spread or halt this virus's spread and circumvent this pandemic condition threatening millions of human lives. The absence of definitive treatment is possible to explore to reduce virus infection and enhance patient recovery. Along with off-label medicines, plasma therapy, vaccines, the researchers exploit the various plants/herbs and their constituents to effectively treat nCoV infection. The present study aimed to present brief and most informative salient features of the numerous facts regarding the SARS-CoV-2, including the structure, genomic sequence, recent mutation, targeting possibility, and various hurdles in research progress, and off-labeled drugs, convalescent plasma therapy, vaccine and plants/herbs for the treatment of coronavirus disease-2019 (COVID-19). Results showed that off-labeled drugs such as hydroxychloroquine, dexamethasone, tocilizumab, antiviral drug (remdesivir, favipiravir), etc., give positive results and approved for use or approved for restricted use in some countries like India. Future research should focus on these possibilities that may allow the development of an effective treatment for COVID-19.

Recent advances in tumor microenvironment associated therapeutic strategies and evaluation models.

As per a report of the world health organization, an estimated 9.6 million people died due to cancer in 2018, globally. Most of the cancer death attributed to the lack of early detection and effective treatment. In the case of solid tumors, various factors such as leaky vasculature, angiogenesis, interstitial fluid pressure and lymphatic drainage are important in cancer chemotherapy. The poor penetration and retention of the drug/drug delivery system in tumor tissue are most critical issues in the way of effective treatment. In this scenario, the challenges are to design the specific nano-therapeutics with the potential to penetrate inside the adverse condition of tumor microenvironment (TME) including high interstitial pressure region and abnormal vasculature. The modification of nanocarriers surfaces with enzymes, peptides, pH-responsive moieties, antibodies etc. could be a promising strategy to improve the nanocarriers penetration inside the solid tumor. The priming with the drug before the administration of nanotherapeutics may also represents an efficient approach for solid tumor treatment. Further, the growth factors including fibroblast growth factor (FGF), platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF) and their pathways could offer potential targeting opportunities for anticancer treatment. Recently, there is a surge in various approaches and formulation design directed towards abnormal TME for more effective cancer therapy. In this review, various factors related to the poor penetration, retention and specific delivery of chemotherapeutics inside tumor cells/tissues are discussed. The emerging formulations strategies directed to the TME and various methodologies for evaluation of their efficacy are also included in this review.

Drug resistance in cancer: mechanisms and tackling strategies.

Drug resistance developed towards conventional therapy is one of the important reasons for chemotherapy failure in cancer. The various underlying mechanism for drug resistance development in tumor includes tumor heterogeneity, some cellular levels changes, genetic factors, and others novel mechanisms which have been highlighted in the past few years. In the present scenario, researchers have to focus on these novel mechanisms and their tackling strategies. The small molecules, peptides, and nanotherapeutics have emerged to overcome the drug resistance in cancer. The drug delivery systems with targeting moiety enhance the site-specificity, receptor-mediated endocytosis, and increase the drug concentration inside the cells, thus minimizing drug resistance and improve their therapeutic efficacy. These therapeutic approaches work by modulating the different pathways responsible for drug resistance. This review focuses on the different mechanisms of drug resistance and the recent advancements in therapeutic approaches to improve the sensitivity and effectiveness of chemotherapeutics.

Surface modified silk fibroin nanoparticles for improved delivery of doxorubicin: Development, characterization, in-vitro studies.

Silk fibroin nanoparticles possess the hydrophobic nature which assists them to become a good substrate for reticulo-endothelial system (RES) and macrophageal uptake. Surface coating of these nanoparticles with hydrophilic stabilizers, like Tween-80 make them long circulating and facilitate their uptake by low density lipoprotein (LDL) receptors to cross blood brain barrier (BBB). Surface modified silk fibroin nanoparticles bearing anti-cancer agent doxorubicin (DOX) were fabricated by desolvation method and coated with Tween-80 as surface modifier. The prepared nanoparticles were characterized for various physicochemical parameters, like particle size, surface charge, surface morphology by scanning electron microscope (SEM) and transmission electron microscopy (TEM), and in vitro drug release along with in vitro cell cytotoxicity, flow cytometry and cellular uptake studies by flourocytometry on glioblastoma cell lines. Entrapment efficiency for the silk fibroin nanoparticles were found to be >85% for coated and uncoated nanoparticles. Nanoparticles with average diameter less than 150 nm having negative charge were found to show no toxicity of its own. The pro-inflammatory response of nanoparticles was observed by determining the cytokines level, such as TNF-α and IL-1ß. Sustained drug release pattern from the nanoparticles with better cytotoxicty as compared to free drug was observed, signifying their potential ability to work as a drug delivery system.

Molecular determinants as therapeutic targets in cancer chemotherapy: An update.

It is well known that cancer cells are heterogeneous in nature and very distinct from their normal counterparts. Commonly these cancer cells possess different and complementary metabolic profile, microenvironment and adopting behaviors to generate more ATPs to fulfill the requirement of high energy that is further utilized in the production of proteins and other essentials required for cell survival, growth, and proliferation. These differences create many challenges in cancer treatments. On the contrary, such situations of metabolic differences between cancer and normal cells may be expected a promising strategy for treatment purpose. In this article, we focus on the molecular determinants of oncogene-specific sub-organelles such as potential metabolites of mitochondria (reactive oxygen species, apoptotic proteins, cytochrome c, caspase 9, caspase 3, etc.), endoplasmic reticulum (unfolded protein response, PKR-like ER kinase, C/EBP homologous protein, etc.), nucleus (nucleolar phosphoprotein, nuclear pore complex, nuclear localization signal), lysosome (microenvironment, etc.) and plasma membrane phospholipids, etc. that might be exploited for the targeted delivery of anti-cancer drugs for therapeutic benefits. This review will help to understand the various targets of subcellular organelles at molecular levels. In the future, this molecular level understanding may be combined with the genomic profile of cancer for the development of the molecularly guided or personalized therapeutics for complete eradication of cancer.

Models for acne: A comprehensive study.

Acne vulgaris (AV) is the familiar chronic skin ailment affecting most of the individuals. This multifarious, disease involves the bacterium gram-positive, anaerobic Propionibacterium acnes (P. acnes) which resides on skin microflora, and participated in acne inflammation and acne lesions. The object of this review is to discuss presently available in vitro, ex vivo, and in vivo models to evaluate the cosmetic formulations that are developed for dealing and prevention of acne formation. These various available models offer new chances for further research on biologically active materials, drugs & pharmaceutical as well as cosmetics for acne treatment.