Therapeutic Entities Research Articles

Translation of gene therapy strategies for amyotrophic lateral sclerosis.

Gene therapy (GT) can correct genetic deficiencies through the modulation of gene expression by gene replacement, addition, silencing, or editing. GT can be administered directly to the patient (in vivo), or in patient-derived cells > (ex vivo), which are then autologously transplanted to the patient. GT delivers nucleic acids [i.e., antisense oligonucleotides (ASOs) or siRNA to silence mRNA], or viral vectors [i.e., lentiviral vectors (LV) for local transduction or adeno-associated viral vectors (AAV) for stable, widespread, and safe gene expression]. Color code: gray represents diseased state, pink indicates therapeutic entities and their effects.

Computational Strategies to Identify New Drug Candidates against Neuroinflammation.

Increasing application of computational approaches in these last decades has deeply modified the process of discovery and commercialization of new therapeutic entities. This is especially true in the field of neuroinflammation, in which both the peculiar anatomical localization and the presence of the blood-brain barrier make it mandatory to finely tune the candidates' physicochemical properties from the early stages of the discovery pipeline. The aim of this review is, therefore, to provide a general overview of neuroinflammation to the readers, together with the most common computational strategies that can be exploited to discover and design small molecules controlling neuroinflammation, especially those based on the knowledge of the three-dimensional structure of the biological targets of therapeutic interest. The techniques used to describe the molecular recognition mechanisms, such as molecular docking and molecular dynamics, will therefore be discussed, highlighting their advantages and limitations. Finally, we report several case studies in which computational methods have been applied to drug discovery for neuroinflammation, focusing on the research conducted in the last decade.

G protein-coupled receptor signaling: transducers and effectors.

G protein-coupled receptors (GPCRs) are of considerable interest due to their importance in a wide range of physiological functions and in a large number of Food and Drug Administration (FDA)-approved drugs as therapeutic entities. With continued study of their function and mechanism of action, there is a greater understanding of how effector molecules interact with a receptor to initiate downstream effector signaling. This review aims to explore the signaling pathways, dynamic structures, and physiological relevance in the cardiovascular system of the three most important GPCR signaling effectors: heterotrimeric G proteins, GPCR kinases (GRKs), and β-arrestins. We will first summarize their prominent roles in GPCR pharmacology before transitioning into less well-explored areas. As new technologies are developed and applied to studying GPCR structure and their downstream effectors, there is increasing appreciation for the elegance of the regulatory mechanisms that mediate intracellular signaling and function.

Advances in hPSC expansion towards therapeutic entities: A review.

For use in regenerative medicine, large‐scale manufacturing of human pluripotent stem cells (hPSCs) under current good manufacturing practice (cGMPs) is required. Much progress has been made since culturing under static two‐dimensional (2D) conditions on feeders, including feeder‐free cultures, conditioned and xeno‐free media, and three‐dimensional (3D) dynamic suspension expansion. With the advent of horizontal‐blade and vertical‐wheel bioreactors, scale‐out for large‐scale production of differentiated hPSCs became possible; control of aggregate size, shear stress, fluid hydrodynamics, batch‐feeding strategies, and other process parameters became a reality. Moving from substantially manipulated processes (i.e., 2D) to more automated ones allows easer compliance to current good manufacturing practices (cGMPs), and thus easier regulatory approval. Here, we review the current advances in the field of hPSC culturing, advantages, and challenges in bioreactor use, and regulatory areas of concern with respect to these advances. Manufacturing trends to reduce risk and streamline large‐scale manufacturing will bring about easier, faster regulatory approval for clinical applications.

Combination of IM-Based Approaches to Unravel the Coexistence of Two Conformers on a Therapeutic Multispecific mAb.

Multispecific antibodies, which target multiple antigens at once, are emerging as promising therapeutic entities to offer more effective treatment than conventional monoclonal antibodies (mAbs). However, these highly complex mAb formats pose significant analytical challenges. We report here on the characterization of a trispecific antibody (tsAb), which presents two isomeric forms clearly separated and identified with size exclusion chromatography coupled to native mass spectrometry (SEC-nMS). Previous studies showed that these isomers might originate from a proline cis/trans isomerization in one Fab subunit of the tsAb. We combined several innovative ion mobility (IM)-based approaches to confirm the isomeric nature of the two species and to gain new insights into the conformational landscape of both isomers. Preliminary SEC-nIM-MS measurements performed on a low IM resolution instrument provided the first hints of the coexistence of different conformers, while complementary collision-induced unfolding (CIU) experiments evidenced distinct gas-phase unfolding behaviors upon activation for the two isomers. As subtle conformational differences remained poorly resolved on our early generation IM platform, we performed high-resolution cyclic IM (cIM-MS) to unambiguously conclude on the coexistence of two conformers. The cis/trans equilibrium was further tackled by exploiting the IMn slicing capabilities of the cIM-MS instrument. Altogether, our results clearly illustrate the benefits of combining state-of-the-art nMS and IM-MS approaches to address challenging issues encountered in biopharma. As engineered antibody constructs become increasingly sophisticated, CIU and cIM-MS methodologies undoubtedly have the potential to integrate the drug development analytical toolbox to achieve in-depth conformational characterization of these products.

Investigation of the Anti-Inflammatory Activity of Fusaproliferin Analogues Guided by Transcriptome Analysis.

Background: Excessive inflammation results in severe tissue damage as well as serious acute or chronic disorders, and extensive research has focused on finding new anti-inflammatory hit compounds with safety and efficacy profiles from natural products. As promising therapeutic entities for the treatment of inflammation-related diseases, fusaproliferin and its analogs have attracted great interest. However, the underlying anti-inflammatory mechanism is still poorly understood and deserves to be further investigated. Methods: For the estimation of the anti-inflammatory activity of fusaproliferin (1) and its analogs (2-4) in vitro and in vivo, lipopolysaccharide (LPS)-induced RAW264.7 macrophages and zebrafish embryos were employed. Then, transcriptome analysis was applied to guide subsequent western blot analysis of critical proteins in related signaling pathways. Surface plasmon resonance assays (SPR) combined with molecular docking analyses were finally applied to evaluate the affinity interactions between 1-4 and TLR4 and provide a possible interpretation of the downregulation of related signaling pathways. Results: 1-4 significantly attenuated the production of inflammatory messengers, including nitric oxide (NO), reactive oxygen species (ROS), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β), as well as nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), in LPS-induced RAW264.7 macrophages. Transcriptome analyses based on RNA-seq indicated the ability of compound 1 to reverse LPS stimulation and the nuclear factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPKs) signaling pathways contribute to the anti-inflammatory process. Experimental verification at the protein level revealed that 1 can inhibit the activation of inhibitor of NF-κB kinase (IKK), degradation of inhibitor of NF-κB (IκB), and phosphorylation of NF-κB and reduce nuclear translocation of NF-κB. 1 also decreased the phosphorylation of MAPKs, including p38, extracellular regulated protein kinases (ERK), and c-Jun N-terminal kinase (JNK). SPR assays and molecular docking results indicated that 1-4 exhibited affinity for the TLR4 protein with KD values of 23.5-29.3μM. Conclusion: Fusaproliferin and its analogs can be hit compounds for the treatment of inflammation-associated diseases.

The 2021 Global Lung Cancer Therapy Landscape

IntroductionThe lung cancer treatment landscape has substantially evolved over the past decade. However, a systematic analysis of the current global drug development landscape has not been conducted. MethodsWe curated and analyzed a comprehensive list of therapeutic entities (TEs) in preclinical development and clinical trials for lung cancer. ResultsOn the basis of our analysis of 707 TEs, we found a consistent forward trajectory in the development pipeline for both NSCLC and SCLC. Most of the TEs were in the advanced stages of clinical trials. Targeted therapies continue to dominate in the non–immuno-oncology space. Immuno-oncology targets are expanding beyond inhibitors of the programmed death-ligand 1 axis. ConclusionsOur analysis highlights a robust portfolio of both preclinical and clinical TEs and suggests that lung cancer treatment is going to become even more biomarker-driven.

Thiazole Scaffold: An Overview on Its Synthetic and Pharmaceutical Aspects

Thiazole and its derivatives have risen to prominence as an important scaffold, attracting the attention of researchers in the area of medicinal chemistry due to their remarkable variety of biological activities. The thiazole moiety has been identified as an essential component in the structure of therapeutic agents including Ravuconazole, Sulfathiazole, Meloxicam, and Ritonavir, and is extensively utilized as an antimicrobial, anticancer, anti-inflammatory, antioxidant, and antiretroviral agent. The thiazole moiety's versatility has already been shown by the vast use of its derivatives with anticancer, anti-HIV, antibacterial, anti-inflammatory, antiallergic, antioxidant, and analgesic actions. For its unique potential in various activities, this moiety's broad array of living response accounts has captivated numerous researchers. This study aims to further the biological potential of thiazole derivatives, whether as a core moiety or as a substituent, to eventually synthesize a diverse array of therapeutic entities.

Near infrared triggered chemo-PTT-PDT effect mediated by glioma directed twin functional-chimeric peptide-decorated gold nanoroses.

The successful application of nanomedicine against glioma is basically hooked on to the fabrication of specific and efficient glioma targeted multifunctional theranostics. Herein, through an easy synthetic methodology, we fabricated a type of novel multifunctional theranostic nanoplatform comprising of anisotropic gold nanoroses (AuNs) co-loaded with doxorubicin (DOX) and the near-infrared (NIR) active/responsive dye, indocyanine green (ICG). The tailored nanotheranostics upon being exposed to NIR laser helped in achieving combinatorial chemo-phototherapy along with optical cell imaging. BBB/glioma-targeting ability was realized by amalgamating the AuNs with a naive peptide drug with BBB-glioma targeting and anti-glioma twin functionality. Efficacy studies carried out in C6 cells and spheroids demonstrated heightened synergistic glioma chemo-PDT-PTT effect (~85% ablation in C6 cells and~88% in C6 spheroids) by the AuNDIPs as compared to the individual therapeutic entities. Here, the AuNs derived nanophototheranostics with in force targeting and on-demand drug release nature will further aid in abolishing chemotherapy associated adverse events by adopting a combinatorial approach for synergistic glioma eradication.

Beyond the Code: Noncoding RNAs in Skin Wound Healing.

An increasing number of noncoding RNAs (ncRNAs) have been found to regulate gene expression and protein functions, playing important roles in diverse biological processes and diseases. Their crucial functions have been reported in almost every cell type and all stages of skin wound healing. Evidence of their pathogenetic roles in common wound complications, such as chronic nonhealing wounds and excessive scarring, is also accumulating. Given their unique expression and functional properties, ncRNAs are promising therapeutic and diagnostic entities. In this review, we discuss current knowledge about the functional roles of noncoding elements, such as microRNAs, long ncRNAs, and circular RNAs, in skin wound healing, focusing on in vivo evidence from studies of human wound samples and animal wound models. Finally, we provide a perspective on the outlook of ncRNA-based therapeutics in wound care.

Amphiphilic Triazine-Phosphorus Metallodendrons Possessing Anti-Cancer Stem Cell Activity.

Dendritic molecules bearing metal complexes in their structure (metallodendrimers and metallodendrons) are considered prospective therapeutic entities. In particular, metallodendrons raise interest as antitumor agents for the treatment of poorly curable or drug-resistant tumors. Herein, we have synthesized amphiphilic triazine-phosphorus dendrons bearing multiple copper (II) or gold (III) complexes on the periphery and a branched hydrophobic fragment at the focal point. Due to their amphiphilic nature, metallodendrons formed single micelles (mean diameter ~9 nm) or multi-micellar aggregates (mean diameter ~60 nm) in a water solution. We have tested the antitumor activity of amphiphilic metallodendrons towards glioblastoma, a malignant brain tumor with a notoriously high level of therapy resistance, as a model disease. The metallodendrons exhibit higher cytotoxic activity towards glioblastoma stem cells (BTSC233, JHH520, NCH644, and SF188 cell lines) and U87 glioblastoma cells (IC50 was 3–6 µM for copper-containing dendron and 11–15 µM for gold-containing dendron) in comparison with temozolomide (IC50 >100 µM)—the clinical standard of care for glioblastoma. Our findings show the potential of metallodendron-based nanoformulations as antitumor entities.

Beneficial effects of seaweeds and seaweed-derived bioactive compounds: Current evidence and future prospective

Seaweeds are the ocean's living resources. Despite their widespread use in the food and feed industries, they are untapped as a nutraceutical and medicinal products despite their significant antioxidative qualities. Seaweeds contain various bioactive chemicals and secondary metabolites that can be employed in the pharmaceutical and nutraceutical industries, cosmetics, fertilizer, and food sectors. Dietary fibers, antioxidants, vital amino acids, phytochemicals, vitamins, polyunsaturated fatty acids, and minerals are abundant in seaweeds that can be majorly used in different aspects. In addition, seaweeds are the chief sources of commercially important agar, carrageenan and alginate. Seaweeds are effective as therapeutic pharmacological entities for various disorders, including dyslipidemia, obesity, diabetes, cancer, and hypertension. Along with individualized health care, a regular diet rich in seaweeds can boost the nutritional content of food. The diverse bioactive components of seaweeds and their nutritional, pharmacological, clinical, biochemical, and industrial applications for human welfare have been the focus of this review. In addition, we have explored how these seaweeds can be used as effective biofertilizers and renewable bioenergy sources in the future. • Seaweeds and seaweed-derived bioactive compounds have a great role in human as a beneficial element. • Seaweeds can be used as Nutrition, Antioxidants and can be used in ROS associated disease in human health. • Seaweeds can be used as Biofertilizer, Bioenergetics, and different industrial applications.

Improving Isolation of Extracellular Vesicles by Utilizing Nanomaterials.

Extracellular vesicles (EVs) as the new form of cellular communication have been demonstrated their potential use for disease diagnosis, prognosis and treatment. EVs are vesicles with a lipid bilayer and are present in various biofluids, such as blood, saliva and urine. Therefore, EVs have emerged as one of the most appealing sources for the discovery of clinical biomarkers. However, isolation of the target EVs from different biofluids is required for the use of EVs as diagnostic and therapeutic entities in clinical settings. Owing to their unique properties and versatile functionalities, nanomaterials have been widely investigated for EV isolation with the aim to provide rapid, simple, and efficient EV enrichment. Herein, this review presents the progress of nanomaterial-based isolations for EVs over the past five years (from 2017 to 2021) and discusses the use of nanomaterials for EV isolations based on the underlying mechanism in order to offer insights into the design of nanomaterials for EV isolations.

Current Designs of Polymeric Platforms Towards the Delivery of Nucleic Acids Inside the Cells with Focus on Polyethylenimine.

Gene delivery is a promising technology for treating diseases linked to abnormal gene expression. Since nucleic acids are the therapeutic entities in such approach, a transfecting vector is required because the macromolecules are not able to efficiently enter the cells by themselves. Viral vectors have been evidenced to be highly effective in this context; however, they suffer from fundamental drawbacks, such as the ability to stimulate immune responses. The development of synthetic vectors has accordingly emerged as an alternative. Gene delivery by using non-viral vectors is a multi-step process that poses many challenges, either regarding the extracellular or intracellular media. We explore the delivery pathway and afterwards, we review the main classes of non-viral gene delivery vectors. We further focus on the progresses concerning polyethylenimine-based polymer-nucleic acid polyplexes, which have emerged as one of the most efficient systems for delivering genetic material inside the cells. The complexity of the whole transfection pathway, along with a lack of fundamental understanding, particularly regarding the intracellular trafficking of nucleic acids complexed to non-viral vectors, probably justifies the current (beginning of 2021) limited number of formulations that have progressed to clinical trials. Truly, successful medical developments still require a lot of basic research. Advances in macromolecular chemistry and high-resolution imaging techniques will be useful to understand fundamental aspects towards further optimizations and future applications. More investigations concerning the dynamics, thermodynamics and structural parameters of polyplexes would be valuable since they can be connected to the different levels of transfection efficiency hitherto evidenced.

Identification of Active Phytochemical from Traditional Herbal Knowledge-base Targeting Pantothenate Synthetase for Anti-tuberculosis Therapy

Increased numbers of reported cases of Mycobacterium tuberculosis (Mtb) resistance to the generally used antibiotics demand to identify novel therapeutic entities for better control of Tuberculosis. Most of the Structure-based Drug Discovery (SBDD) works reported earlier had screened compounds against a single drug target to avoid any off-target binding and related complications. Because of the development of Multi-Drug Resistant and Extensively Drug-Resistant strains of Mtb and looking into the incurable pathologies, targeting the right drug target with a promising ligand data set will result in effective therapeutics. Simultaneously, traditional knowledge-based drugs have earned little success in developing anti-tuberculosis drugs in recent studies. Combining the right-target approach and traditional herbal knowledge base, this in silico drug discovery study was carried out where 1236 compounds from two plants, traditionally used for TB treatment, Camellia sinensis, Ginkgo biloba along with the antibacterial compounds of DrugBank Database have been screened against Pantothenate synthetase of Mtb, a well-known drug target for anti-TB therapeutics. Through this analytics, Epigallocatechin gallate (EGCG) of Camellia sinensis has been reported through in silico docking studies and subsequent Molecular Dynamics simulation, as a promising anti-TB candidate due to its affinity towards Pantothenate synthetase of Mtb. EGCG was subjected to ADME-Tox studies as well as 3D QSAR analysis for the detection of its drug-like properties and for the determination of IC50 value. The EGCG showed the IC50 value at 1404 nM, which is quite promising for a plant-origin compound. The selected ligand, EGCG, due to its promising affinity towards Pantothenate synthetase of Mtb with high drug-like properties, justifies its selection as a potential anti-tuberculosis compound.

Hydrogels: 3D Drug Delivery Systems for Nanoparticles and Extracellular Vesicles.

Synthetic and naturally occurring nano-sized particles present versatile vehicles for the delivery of therapy in a range of clinical settings. Their small size and modifiable physicochemical properties support refinement of targeting capabilities, immune response, and therapeutic cargo, but rapid clearance from the body and limited efficacy remain a major challenge. This highlights the need for a local sustained delivery system for nanoparticles (NPs) and extracellular vesicles (EVs) at the target site that will ensure prolonged exposure, maximum efficacy and dose, and minimal toxicity. Biocompatible hydrogels loaded with therapeutic NPs/EVs hold immense promise as cell-free sustained and targeted delivery systems in a range of disease settings. These bioscaffolds ensure retention of the nano-sized particles at the target site and can also act as controlled release systems for therapeutics over a prolonged period of time. The encapsulation of stimuli sensitive components into hydrogels supports the release of the content on-demand. In this review, we highlight the prospect of the sustained and prolonged delivery of these nano-sized therapeutic entities from hydrogels for broad applications spanning tissue regeneration and cancer treatment. Further understanding of the parameters controlling the release rate of these particles and efficient transfer of cargo to target cells will be fundamental to success.

The effectiveness of medical antibiotics and herbs as antibiotic on mouth bacterial flora

Background Plant are the oldest source of pharmacological active compounds. The Achyranthes aspera's seeds, roots and shoots are used as medicine from ancient times. Oral infections and oral disease are directly depends on the oral application of our daily lives. The present study gives information on anti-bacterial properties of this plant. The role of this plant against bacteria have been screened and confirmed by many researchers. While many people in the villages of India also use the roots of this plant as tooth brush, it still has a long way to go to be established as a recognized entity in the prevention and treatment of oral infections and oral diseases. Various studies report that the aqueous solution of A. aspera has shown antibacterial activity against Staphylococcus aureus, Streptococcus heamolyticus, and Bacillus typhosus, while alcoholic and aqueous extract of its leaves possess antibacterial activity against S. aureus and Escherichia coli. Till today, very few studies have been conducted on the antibacterial effect of the extracts of A. aspera against mouth bacterial flora and oral pathogens. Therefore, the aim of this study is to evaluate the antibacterial activities of the extracts of A. aspera against mouth bacterias like S. aureus, E-coli, Staphylococcus aureus etc. Objective The aim of this study was to evaluate the antibacterial activities of the extracts of Achyranthes aspera against mouth bacterial flora and compare it's effectiveness with common antibiotics that we generally adviced by the physician in medical field. Methods: A observation study with quantitative approach was used to conduct a comprehensive assessment of the common bacteria of the saliva of different people. With scientific perspective the data was made and analysis of it's effectiveness as anti-bacteria. The effect of broad aspectrum antibiotics were used to examine association between the effects of Achyranthes aspera on common bacterias of saliva like S. aureus, E-coli, Staphylococcus aureus in terms of zone of inhibition. Results The study showed the effect of extracts (EES, EEL, MES, MEL, IES, IEL) on mouth bacterial flora. On Pseudomonos species the highest effect showed by Ethanolic extracts of stem and Methanolic extracts of leaves. All the data that the extracts of leaves and stem of Achyranthes aspera are effective against mouth bacterial flora. The study also compares the effect of selected antibiotics with the effect of extracts of Achyranthes aspera. On E. coli, the effects of ethanolic extracts of leaf was greater than the effects of AZM and LE but lower than that of CX. Discussion These data comprehensively summarize the measurable difference between the effects of different extracts of Achyranthes aspera on bacteria and between the effect of antibiotics and effect of extracts of Achyranthes aspera. These data were collected statistically based on the objectives of the study. Recommendation In the light of the finding and personal experience of the researches, the following recommendations are put forth. The findings of the present study can be used as a guide for future study A similar study can be conducted in a large representative sample for better generalization A similar study can be conducted on individuals with some kind of oral infection to assess the efficacy of the herbs A similar study can be conducted on multidrug resistant bacteria using the same extracts A comparative study can be conducted to established differences in effects between extracts of A. aspera and other drugs used for mouth rinsing. Conclusion Much advancement in the treatment and prevention of bacterial infections has been introduced over the past century. Medicinal plants are pluripotent in nature and hence offer great therapeutic entities for the health sciences. If the strengths of the knowledge based traditional herbal medicine combined with the scientific methods of drug preparation, it can provide new and more advanced functional leads to reduce time, money and toxicity - the three main hurdles in drug development. As the result of the present study exhibited presence of antibacterial properties in the studied extracts of A. aspera, this also indicates that active bio-molecule is present in each extract. Hence, they can be utilized along with conventional medicine that can assure us of greater health in the future. Further studies can be conducted in future to assess the safety levels of this herb.

Immunomodulatory Effects of a Concoction of Natural Bioactive Compounds-Mechanistic Insights.

Natural bioactive compounds derived from plant-based products are known for their biological immunomodulatory activities. They possess systemic pleiotropic effects, minimal side effects, and very low toxicities. Plant-based bioactive compounds have tremendous potential as natural therapeutic entities against various disease conditions and act as anti-inflammatory, antioxidant, anti-mutagenic, anti-microbial, anti-viral, anti-tumour, anti-allergic, neuroprotective, and cardioprotective agents. A herbal formulation extract including five biologically active compounds: Apigenin, Quercetin, Betulinic acid, Oleanolic acid, and β-Sitosterol can impart several immunomodulatory effects. In this review, we systematically present the impact of these compounds on important molecular signaling pathways, including inflammation, immunity, redox metabolism, neuroinflammation, neutropenia, cell growth, apoptosis, and cell cycle. The review corroborates the beneficial effect of these compounds and shows considerable potential to be used as a safer, more cost-effective treatment for several diseases by affecting the major nodal points of various stimulatory pathways.

Financial liquidity and profitability of polish self-governing public health care institutions for the years 2016-2018.

Currently, Polish therapeutic entities are forced to operate in an extremely turbulent environment and pursue two main goals: economic and social. The aim of this article is to diagnose the relationship between profitability and financial liquidity in Polish self-government health care institutions by assessing basic indicators of financial liquidity and profitability. The scope of work covered 1017 self-government independent health care institutions, which systematically published their financial statements for 2016-2018. The subject of the study was to analyze the relationship between the levels of profitability and financial liquidity ratios. The study used statistical and tabular-descriptive methods. On the basis of the obtained results it can be stated that the relation between the return on sales, return on equity and return on assets and liquidity (current, fast and immediate) was positive and the strength of this relation was strong and statistically significant. There was a statistically significant negative correlation between short-term liabilities and the return on sales, assets and equity. The cash conversion cycle has a significant positive impact on profitability (and vice versa). CONCLUSION. Entities that had higher profitability also had a higher degree of liquidity. They were also more efficient in inventory management and paid their liabilities faster. Summarizing the results of the study, it can be concluded that those entities that had higher profitability also had a higher degree of liquidity. They were also more efficient in inventory management and paid their liabilities faster.

Does skin permeation kinetics influence efficacy of topical dermal drug delivery system?: Assessment, prediction, utilization, and integration of chitosan biomacromolecule for augmenting topical dermal drug delivery in skin.

Skin permeation is an integral part of penetration of topical therapeutics. Zero order in addition to Higuchi permeation kinetic is usually preferred in topical drug delivery cargo. Penetration of therapeutic entities through epidermal barrier is a major challenge for scientific fraternity. Furthermore, penetration of therapeutic entities determines the transportation and ultimately therapeutic efficacy of topical dermal dosage forms. Apart from experimentation models, mathematical equations, in silico docking, molecular dynamics (MDs), and artificial neural network (Neural) techniques are being used to assess free energies and prediction of electrostatic attractions in order to predict the permeation phenomena of therapeutic entities. Therefore, in the present review, we have summarized the significance of kinetic equations, in silico docking, MDs, and ANN in assessing and predicting the penetration behavior of topical therapeutics through dermal dosage form. In addition, the role of chitosan biomacromolecule in modulating permeation of topical therapeutics in skin has also been illustrated using computational techniques.