Fabrication and in vitro characterization of curcumin film-forming topical spray: An integrated approach for enhanced patient comfort and efficacy.

Background: Curcumin, known for its anti-inflammatory properties, was selected for the developing consumer friendly film forming spray that offers precise delivery of curcumin and and improves patient adherence. Methods: An optimized film-forming solution was prepared by dissolving curcumin (1%), Eudragit RLPO (5%), propylene glycol (1%), and camphor (0.5%) in ethanol: acetone (20:80) as the solvent. The solution was filled in a spray container which contained 70% solutions and 30% petroleum gas. In-vitro characterization was performed. Results: Potential anti-inflammatory phytoconstituents were extracted from the PubChem database and prepared as ligands, along with receptor molecules (nsp10-nsp16), for molecular docking using Autodock Vina. The docking study showed the lowest binding energy of -8.2 kcal/mol indicates better binding affinities. The optimized formulation consisted of ethanol:acetone (20:80) as the solvent, Eudragit RLPO (5%) as the polymer, propylene glycol (1%) as the plasticizer, and camphor oil (0.5%) as the penetration enhancer. The optimized formulation exhibited pH of 5.8 ± 0.01, low viscosity, low film formation time (19.54 ± 0.78 sec), high drug content (8.243 ± 0.43 mg/mL), and extended ex vivo drug permeation (85.08 ± 0.09%) for nine hours. Consequently, the formulation was incorporated into a container using 30% liquefied petroleum gas, delivering 0.293 ± 0.08 mL per actuation, containing 1.53 ± 0.07 mg of the drug. The film-forming spray exhibited higher cumulative drug permeation (83.94 ± 0.34%) than the marketed cream formulation and pure drug solution after 9 h, with an enhancement ratio of 14. Notably, the film-forming spray exhibited no skin irritation and remained stable for over three months. Conclusions: The developed curcumin film-forming system is promising as a carrier for wound management because of its convenient administration and transport attributes. Further in vivo studies are required to validate its efficacy in wound management.

Simultaneous quantification of 4-hydroxytamoxifen and hesperidin in liposomal formulations: Development and validation of a RP-HPLC method.

Breast cancer treatment options are diverse, with tamoxifen commonly used as a selective estrogen receptor modulator (SERM) for hormone receptor-positive breast cancer. However, tamoxifen can have adverse systemic effects. Local transdermal therapy offers a potential solution by delivering the drug directly to the breast and minimizing systemic exposure. Hesperidin, a flavonoid, exerts synergistic effects when combined with anticancer agents. This combination therapy may be a more effective approach to breast cancer management. Analytical methods have been developed to quantify 4-Hydroxytamoxifen (4-HT) and hesperidin separately; however, no method currently exists for their simultaneous quantification in pharmaceutical formulations. This study aimed to develop and validate a reverse-phase high-performance liquid chromatography (RP-HPLC) method for the simultaneous quantification of 4-HT and hesperidin in liposomal formulations. A Design of Experiments (DoE) approach was employed using a Box-Behnken design (BBD) to optimize the RP-HPLC method. BBD allowed for a reduction in the number of required tests by creating a statistical model to estimate the significance of various factors and interactions. The methanol concentration, flow rate, and injection volume were considered as independent variables for optimization. A mobile phase (90:10 ratio of methanol: 0.1% v/v orthophosphoric acid) with a flow rate of 0.4 mL/min, and an injection volume of 10 µL was selected as optimized chromatographic condition. 4-HT showed a retention time (Rt) of 5.05 min and hesperidin showed an Rt of 7.11 min using an optimized analytical method and was detected at 275 nm. The developed RP-HPLC method was validated according to the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) guidelines, confirming its accuracy, precision, linearity, selectivity, and robustness. The validated method was then successfully applied to determine the entrapment efficiency and permeation of 4-HT and hesperidin into loaded liposomes. This study fills a gap in the literature by providing a simple and reliable RP-HPLC method for the simultaneous quantification of 4-HT and hesperidin in liposomal formulations.

Non-systemic Approaches for Ductal Carcinoma In Situ: Exploring the Potential of Ultra-flexible Combisomes as a Novel Drug Delivery Strategy-a Review.

Ductal carcinoma in situ (DCIS) is currently treated through breast-conserving surgery (lumpectomy), radiation therapy, breast-removing surgery (mastectomy), and hormone therapy to prevent further progression into invasive breast cancer and recurrence. Discrepancies concerning the prognosis of DCIS have sparked controversy about adequate treatment. Considering the severe medical and psychological consequences of mastectomy, developing a treatment approach that arrests the progression of DCIS to the invasive stage without affecting the non-cancerous cells is of utmost importance. In the current review, the problems associated with the diagnosis and management of DCIS have been thoroughly discussed. A summary of the route of administration and drug delivery systems to manage DCIS was also provoked. Innovative ultra-flexible combisomes were also proposed for the effective management of DCIS. Prevention is essential in managing the risk of DCIS and reducing the risk of progression to invasive breast cancer. While prevention is vital, it is not always possible to prevent DCIS, and in some cases, treatment may be necessary. Hence, this review recommends that ultra-flexible combisomes administered as a topical gel provide a non-systemic approach for managing DCIS and thus significantly minimize the side effects and costs associated with existing therapies.

Cyclin-dependent kinases as potential targets for colorectal cancer: past, present and future.

Colorectal cancer (CRC) is a common cancer in the world and its prevalence is increasing in developing countries. Deregulated cell cycle traverse is a hallmark of malignant transformation and is often observed in CRC as a result of imprecise activity of cell cycle regulatory components, viz. cyclins and cyclin-dependent kinases (CDKs). Apart from cell cycle regulation, some CDKs also regulate processes such as transcription and have also been shown to be involved in colorectal carcinogenesis. This article aims to review cyclin-dependent kinases as potential targets for CRC. Furthermore, therapeutic candidates to target CDKs are also discussed.

SARS-CoV 2 spike protein S1 subunit as an ideal target for stable vaccines: A bioinformatic study.

The Covid-19 a pandemic infectious disease and affected life across the world resulting in over 188.65 million confirmed cases across 223 countries, territories and areas with 4.06 million deaths. It is caused by a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and spike (S) protein of SARS-CoV-2, which plays a key role in the receptor recognition and cell membrane fusion process, is composed of two subunits, S1 and S2. The S1 subunit contains a receptor-binding domain (RBD) that recognizes and binds to the host receptor angiotensin-converting enzyme 2 (ACE2), while the S2 subunit mediates viral cell membrane fusion. Hence, it is a key target for developing neutralizing antibodies. Here, we have performed phylogenetic analysis and structural modeling of the SARS-CoV-2 spike glycoprotein, which is found highly conserved. The overall percent protein sequence identity from the SARS-CoV-2 spike protein sequences from the NCBI database was 99.68%. The functional domains of the S protein reveal that the S1 subunit was highly conserved (99.70%) than the S2 subunit (99.66%). Further, the 319-541 residues (RBD) of amino acids within the S1 domain were 100% similar among the spike protein. The 3D modeling of SARS-CoV-2 spike glycoprotein indicated that S protein has four domains with five protein units and the S1 subunit from 1 to 289 amino acid of domain 1 is highly conserved without any change in the ligand interaction site. This analysis clearly suggests that the S1 subunit (RBD 319-541) can be used as a target region for stable and safe vaccine development.

Intercellular adhesion molecule-1 is a surrogate biomarker for subclinical atherosclerosis in Type 2 diabetes mellitus.

Aim: We aimed to investigate biomarkers of inflammation, oxidative stress as surrogate markers of subclinical atherosclerosis in patients with Type 2 diabetes mellitus (T2DM). Materials & methods: Subjects were grouped based on carotid intima media thickness (CIMT). Group 1: healthy controls (CIMT <0.57 mm); Group 2: T2DM without subclinical atherosclerosis (CIMT <0.57 mm); Group 3: T2DM with subclinical atherosclerosis (CIMT ≥0.57 mm). Results: Significantly higher MDA, Hs-CRP, Ox-LDL, PTX-3, IL-6, ICAM-1 and lower FRAP, IL-10 levels in T2DM groups compared with controls (p = 0.001). Changes were more significant in Group 3 compared with Group 2. ICAM-1 had the highest sensitivity and specificity at a cut-off value of >40.34 ng/ml compared with Ox-LDL and PTX-3 (p < 0.001). Conclusion: ICAM can be considered as an alternate surrogate biomarker of CIMT.