Sun exposure has been coupled with numerous types of acute and chronic reactions in skin, for example, sun burns, photoimmune suppression, photoaging, and skin cancer. In scrutiny of growing understanding of the potentially unfavorable long-term side effects of solar irradiation, there is a universal call for harmless and effective photoprotectants. Photoprotective agents are used for protection against ultraviolet (UV) radiations. In support of best photoprotective measures, now sunscreens are in great demand. Safeguard from UVB is quantified as a minimal erythema dose-based sun protection factor (SPF). UVA protection testing methods include evaluation of persistent pigment darkening (PPD) and critical wavelength. The rationale of this review is to present the contemporary information on the cutaneous pathophysiology of photooxidative stress, to study different UV filters with their UV spectrum and various commercially available sunscreens, with special emphasis on their active ingredients and SPFs. The characterization of different parameters to evaluate the efficacy of sunscreens, for example, SPF, immune suppression factor, photostability, and water resistance, have been described on the basis of findings from different researchers.
This study was designed for investigating the effect of soybean (SS) extract and chitosan (CTN) in facilitating the permeation of carvedilol (CDL) across rat epidermis.Transdermal flux of carvedilol through heat-separated rat epidermis was investigated in vitro using vertical Keshary-Chien diffusion cells. Biophysical and microscopic manifestations of epidermis treated with SS-extract, CTN, and SS extract-CTN mixture were investigated by using DSC, TEWL, SEM, and TEM. Biochemical estimations of cholesterol, sphingosine, and triglycerides were carried out for treated excised as well as viable rat epidermis. The antihypertensive activity of the patches in comparison to that after oral administration of carvedilol was studied in deoxycorticosterone acetate-induced hypertensive rats.The solubility of CDL was found to be maximum in the presence of 1% (w/v) SS extract. The K(IPM/PB) of CDL decreased with increase in concentration of SS extract. The in vitro permeation of CDL across rat epidermis increased and was maximum with combination of SS extract and chitosan (CTN). Biochemical and microscopic studies revealed the initiation of reversal of barrier integrity after 12 hours. Furthermore, the application of patches containing SS extract-CTN mixture resulted in sustained release of carvedilol, which was able to control the hypertension in deoxycorticosterone acetate (DOCA) induced hypertensive rats through 24 hours. CTN was found to potentiate the permeation enhancing activity of SS extract.The developed transdermal patches of CDL containing SS extract-CTN mixture exhibited better performance as compared to oral administration in controlling hypertension in rats.
Cytochrome P450 1B1, a tumor-specific overexpressed enzyme, significantly impairs the pharmacokinetics of several commonly used anticancer drugs including docetaxel, paclitaxel and cisplatin, leading to the problem of resistance to these drugs. Currently, there is no CYP1B1 inhibition-based adjuvant therapy available to treat this resistance problem. Hence, in the current study, exhaustive in-silico studies including scaffold hopping followed by molecular docking, three-dimensional quantitative structure-activity relationships (3D-QSAR), molecular dynamics and free energy perturbation studies were carried out to identify potent and selective CYP1B1 inhibitors. Initially, scaffold hopping analysis was performed against a well-reported potent and selective CYP1B1 inhibitor (i.e. compound 3n). A total of 200 scaffolds were identified along with their shape and field similarity scores. The top three scaffolds were further selected on the basis of these scores and their synthesis feasibility to design some potent and selective CYP1B1 inhibitors using the aforementioned in-silico techniques. Designed molecules were further synthesized to evaluate their CYP1B1 inhibitory activity and docetaxel resistance reversal potential against CYP1B1 overexpressed drug resistance MCF-7 cell line. In-vitro results indicated that compounds 2a, 2c and 2d manifested IC50 values for CYP1B1 ranging from 0.075, 0.092 to 0.088 μM with at least 10-fold selectivity. At low micromolar concentrations, compounds 1e, 1f, 2a and 2d exhibited promising cytotoxic effects in the docetaxel-resistant CYP1B1 overexpressed MCF-7 cell line. In particular, compound 2a is most effective in reversing the resistance with IC50 of 29.0 ± 3.6 μM. All of these discoveries could pave the way for the development of adjuvant therapy capable of overcoming CYP1B1-mediated resistance.
In vivo skin permeation studies are considered gold standard but are difficult to perform and evaluate due to ethical issues and complexity of process involved. In recent past, a useful tool has been developed by combining the computational modeling and experimental data for expounding biological complexity. Modeling of percutaneous permeation studies provides an ethical and viable alternative to laboratory experimentation. Scientists are exploring complex models in magnificent details with advancement in computational power and technology. Mathematical models of skin permeability are highly relevant with respect to transdermal drug delivery, assessment of dermal exposure to industrial and environmental hazards as well as in developing fundamental understanding of biotransport processes. Present review focuses on various mathematical models developed till now for the transdermal drug delivery along with their applications.
The transdermal route of drug delivery has attracted researchers due to many biomedical advantages associated with it. However, excellent impervious nature of skin is the greatest challenge that has to be overcome for successfully delivering drug molecules to the systemic circulation by this route. Various formulation approaches used to systemically deliver drug molecules include use of prodrugs/lipophilic analogs, permeation enhancers, sub saturated systems and entrapment into vesicular systems. Further, the adhesive mixture, physical system of the delivery system and release liner influence drug release and its permeation across the skin. In addition, great strides in designing delivery systems for maximizing percutaneous drug permeation without comprising with ease of therapy cannot be neglected in improving functionality of transdermal drug delivery systems. This article deals with the innovations pertaining to formulation and techniques as described in recent patents. Keywords: Transdermal drug delivery, transcutaneous permeation, percutaneous permeation, adhesive, microblades, microporation, electroporation, iontophoresis, sonophoresis, microneedles
The main aim of this chapter is the detailed analysis of the Mesodyn module and how it is beneficial in the pharmaceuticals or drug delivery systems. These models are the generalization of a coarse-grained model in mesoscopic dynamics which is used for the field-based simulations of complex systems. A set of functional Langevin equations characterize the system’s behavior. These computer-based simulation tools have been proven effective for providing information at molecular and mesoscopic scales and also for overcoming the limitations of wet lab experiments. So, this chapter will discuss the potential use of Mesodyn simulations in pre-formulations and various other applications for the rational designing of drug delivery systems after providing a brief theoretical background.
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