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Sachin Yadav,1,* Dilip Kumar Arya,1,* Prashant Pandey,1 Sneha Anand,1 Anurag Kumar Gautam,1 Shivendu Ranjan,2 Shubhini A Saraf,1 Vijayakumar Mahalingam Rajamanickam,1 Sanjay Singh,1 Kumarappan Chidambaram,3 Taha Alqahtani,3 Paruvathanahalli Siddalingam Rajinikanth1,4 1Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University, Lucknow, India; 2School of Nano Science and Technology, Indian Institute of Technology Kharagpur, Kharagpur, West Bengal, India; 3Department of Pharmacology and Toxicology, King Khalid University, Abha, Saudi Arabia; 4Department of Pharmaceutical Technology, School of Pharmacy, Taylor’s University Lakeside Campus, Kuala Lumpur Malaysia*These authors contributed equally to this workCorrespondence: Paruvathanahalli Siddalingam Rajinikanth, Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University, Lucknow, 226025, India, Email psrajinikanth222@gmail.comIntroduction: Foot ulceration is one of the most severe and debilitating complications of diabetes, which leads to the cause of non-traumatic lower-extremity amputation in 15– 24% of affected individuals. The healing of diabetic foot (DF) is a significant therapeutic problem due to complications from the multifactorial healing process. Electrospun nanofibrous scaffold loaded with various wound dressing materials has excellent wound healing properties due to its multifunctional action.Purpose: This work aimed to develop and characterize chitosan (CS)-polyvinyl alcohol (PVA) blended electrospun multifunctional nanofiber loaded with curcumin (CUR) and zinc oxide (ZnO) to accelerate diabetic wound healing in STZ-induced diabetic rats.Results: In-vitro characterization results revealed that nanofiber was fabricated successfully using the electrospinning technique. SEM results confirmed the smooth surface with web-like fiber nanostructure diameter ranging from 200 – 250 nm. An in-vitro release study confirmed the sustained release of CUR and ZnO for a prolonged time. In-vitro cell-line studies demonstrated significantly low cytotoxicity of nanofiber in HaCaT cells. Anti-bacterial studies demonstrated good anti-bacterial and anti-biofilm activities of nanofiber. In-vivo animal studies demonstrated an excellent wound-healing efficiency of the nanofibers in STZ–induced diabetic rats. Furthermore, the ELISA assay revealed that the optimized nanofiber membrane terminated the inflammatory phases successfully by downregulating the pro-inflammatory cytokines (TNF-α, MMP-2, and MMP-9) in wound healing. In-vitro and in-vivo studies conclude that the developed nanofiber loaded with bioactive material can promote diabetic wound healing efficiently via multifunction action such as the sustained release of bioactive molecules for a prolonged time of duration, proving anti-bacterial/anti-biofilm properties and acceleration of cell migration and proliferation process during the wound healing.Discussion: CUR-ZnO electrospun nanofibers could be a promising drug delivery platform with the potential to be scaled up to treat diabetic foot ulcers effectively.Graphical Abstract: Keywords: electrospinning, curcumin, zinc oxide, chitosan, polyvinyl alcohol, diabetic wound healing

Drugs based on herbs have become a common form of therapy as well as for prophylaxis because they are often perceived as being natural and therefore harmless. Today they are one of the hottest trends and most sought after in the field of nutrition or herbal therapeutics. As the use of complementary medicine grows, so does the knowledge that many compounds in common use not only have a significant effect on the body but may also interact with pharmaceuticals and also with other alternative products. Concurrent use of herbs with drugs may mimic, magnify, or oppose the effect of drugs leading to herb-drug interactions. Currently, there is very little information published on herb-herb or herb-drug interactions as compared to the use of herbs which is progressively growing across the world. Many reports of herb-drug interactions are sketchy and lack laboratory analysis of suspect preparations. Health-care practitioners should caution patients against mixing herbs and pharmaceutical drugs. The article reviews the recent literature on the adverse effects of herbal remedies including the most widely sold herbal medicinal products, like liquorice, garlic, ginger, green tea, and turmeric, etc., and reinforce the safety aspect of herbal products, which are considered to be relatively safe by common people. [ABSTRACT FROM AUTHOR]

In Ayurveda, Cissus quadrangularis Linn. is used to treat anorexia, asthma, sickle cell, colds, pain, and malaria. Aqueous C. quadrangularis extract was evaluated in vivo for its antiepileptic activity by using the maximal electroshock and isonicotinic hydrazide acid models, for its analgesic activity by using the hot plate method, and for its smooth muscle relaxant activity by using the rotarod method. Adult male Swiss mice were used for this study and animals were divided into 6 animals per group. Doses of 250 mg/kg body weight and 500 mg/kg body weight protected the mice against maximal electroshock seizure, and delayed the onset time of seizures induced by isonicotinic hydrazide acid. Prominent analgesic activity was observed using the hot plate method. The paw licking time was delayed significantly. The extract also displayed prominent smooth muscle relaxant activity. The results suggest that the aqueous extracts of C. quadrangularis roots possess anticonvulsant, analgesic, and smooth muscle relaxant properties. [ABSTRACT FROM AUTHOR]

Venous malformations are one of the commonest anomalies of the vascular tree and their management has always remained a major challenge. Surgery and other treatment modalities are not always satisfactory and have a higher morbidity, recurrence and complication rate. The author retrospectively analyzed 40 patients of venous malformations who underwent sclerotherapy with sodium tetradecyl sulfate solely or as an adjunct to surgery. The purpose of the study was to evaluate the efficacy and safety of sodium tetradecyl sulfate sclerotherapy in the treatment of venous malformations.

Tumescent anesthesia is a now an established technique for regional anesthesia of the skin and the subcutaneous fatty tissue. The unsurpassed simplicity and safely of this procedure have opened up the gates for newer indications. We have employed this technique for harvesting split-thickness grafts in various conditions. We have found that this technique is extremely simple in which large areas can be anesthetized for harvesting split-thickness skin grafts safely. The good passive resistance achieved facilitates easy harvesting of split-thickness grafts along with minimal bleeding and long lasting pain relief. We found this to be an inexpensive, safe and simple technique with elimination of risks and expenses of general anesthesia.

Sebaceous horn or cutaneous horn of the nose is a rare clinical entity. A case of a giant sebaceous horn of the nose presenting in an elderly male, which was successfully excised and reconstructed is reported.

Wounds pose a formidable challenge in healthcare, necessitating the exploration of innovative tissue-healing solutions. Traditional wound dressings exhibit drawbacks, causing tissue damage and impeding natural healing. Using a Microwave (MW)-)-assisted technique, we envisaged a novel hydrogel (Hg) scaffold to address these challenges. This hydrogel scaffold was created by synthesizing a pH-responsive crosslinked material, specifically locust bean gum-grafted-poly(acrylamide-co-acrylic acid) [LBG-g-poly(AAm-co-AAc)], to enable sustained release of c-phycocyanin (C-Pc). Synthesized LBG-g-poly(AAm-co-AAc) was fine-tuned by adjusting various synthetic parameters, including the concentration of monomers, duration of reaction, and MW irradiation intensity, to maximize the yield of crosslinked LBG grafted product and enhance encapsulation efficiency of C-Pc. Following its synthesis, LBG-g-poly(AAm-co-AAc) was thoroughly characterized using advanced techniques, like XRD, TGA, FTIR, NMR, and SEM, to analyze its structural and chemical properties. Moreover, the study examined the in-vitro C-Pc release profile from LBG-g-poly(AAm-co-AAc) based hydrogel (HgCPcLBG). Findings revealed that the maximum release of C-Pc (64.12 ± 2.69 %) was achieved at pH 7.4 over 48 h. Additionally, HgCPcLBG exhibited enhanced antioxidant performance and compatibility with blood. In vivo studies confirmed accelerated wound closure, and ELISA findings revealed reduced inflammatory markers (IL-6, IL-1β, TNF-α) within treated skin tissue, suggesting a positive impact on injury repair. A low-cost and eco-friendly approach for creating LBG-g-poly(AAm-co-AAc) and HgCPcLBG has been developed. This method achieved sustained release of C-Pc, which could be a significant step forward in wound care technology., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Over the period of the preceding decade, artificial intelligence (AI) has proved an outstanding performance in entire dimensions of science including pharmaceutical sciences. AI uses the concept of machine learning (ML), deep learning (DL), and neural networks (NNs) approaches for novel algorithm and hypothesis development by training the machines in multiple ways. AI-based drug development from molecule identification to clinical approval tremendously reduces the cost of development and the time over conventional methods. The COVID-19 vaccine development and approval by regulatory agencies within 1-2 years is the finest example of drug development. Hence, AI is fast becoming a boon for scientific researchers to streamline their advanced discoveries. AI-based FDA-approved nanomedicines perform well as target selective, synergistic therapies, recolonize the theragnostic pharmaceutical stream, and significantly improve drug research outcomes. This comprehensive review delves into the fundamental aspects of AI along with its applications in the realm of pharmaceutical life sciences. It explores AI's role in crucial areas such as drug designing, drug discovery and development, traditional Chinese medicine, integration of multi-omics data, as well as investigations into drug repurposing and polypharmacology studies., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

A prolonged and compromised wound healing process poses a significant clinical challenge, necessitating innovative solutions. This research investigates the potential application of nanotechnology-based formulations, specifically nanofiber (NF) scaffolds, in addressing this issue. The study focuses on the development and characterization of multifunctional nanofibrous scaffolds (AZL-CS/PVA-NF) composed of azilsartan medoxomil (AZL) enriched chitosan/polyvinyl alcohol (CS/PVA) through electrospinning. The scaffolds underwent comprehensive characterization both in vitro and in vivo. The mean diameter and tensile strength of AZL-CS/PVA-NF were determined to be 240.42 ± 3.55 nm and 18.05 ± 1.18 MPa, respectively. A notable drug release rate of 93.86 ± 2.04%, was observed from AZL-CS/PVA-NF over 48 h at pH 7.4. Moreover, AZL-CS/PVA-NF exhibited potent antimicrobial efficacy for Staphylococcus aureus and Pseudomonas aeruginosa. The expression levels of Akt and CD31 were significantly elevated, while Stat3 showed a decrease, indicating a heightened tissue regeneration rate with AZL-CS/PVA-NF compared to other treatment groups. In vivo ELISA findings revealed reduced inflammatory markers (IL-6, IL-1β, TNF-α) within treated skin tissue, implying a beneficial effect on injury repair. The comprehensive findings of the present endeavour underscore the superior wound healing activity of the developed AZL-CS/PVA-NF scaffolds in a Wistar rat full-thickness excision wound model. This indicates their potential as novel carriers for drugs and dressings in the field of wound care., (© 2024. Controlled Release Society.)

Sarcopenia is a musculoskeletal disease that reduces muscle mass and strength in older individuals. The study investigates the effects of azilsartan (AZL) on skeletal muscle loss in natural sarcopenic rats. Male Sprague-Dawley rats aged 4-6 months and 18-21 months were selected as young-matched control and natural-aged (sarcopenic) rats, respectively. Rats were allocated into young and old control (YC and OC) and young and old AZL treatment (YT and OT) groups, which received vehicles and AZL (8 mg/kg, orally) for 6 weeks. Rats were then sacrificed after muscle function analysis. Serum and gastrocnemius (GN) muscles were isolated for further endpoints. AZL significantly improved muscle grip strength and antioxidant levels in sarcopenic rats. AZL also restored the levels of insulin, testosterone, and muscle biomarkers such as myostatin and creatinine kinase in sarcopenic rats. Furthermore, AZL treatment improved the cellular and ultrastructure of GN muscle and prevented the shift of type II (glycolytic) myofibers to type I (oxidative) myofibers. The results showed that AZL intervention restored protein synthesis in natural sarcopenic rats by increasing p-Akt-1 and decreasing muscle RING-finger protein-1 and tumor necrosis factor alpha immunoexpressions. In conclusion, the present findings showed that AZL could be an effective intervention in treating age-related muscle impairments., Competing Interests: There is no competing interest, as stated by the authors.

Past scientific testimonials in the field of glioma research, the deadliest tumor among all brain cancer types with the life span of 10-15 months after diagnosis is considered as glioblastoma multiforme (GBM). Even though the availability of treatment options such as chemotherapy, radiotherapy, and surgery, are unable to completely cure GBM due to tumor microenvironment complexity, intrinsic cellular signalling, and genetic mutations which are involved in chemoresistance. The blood-brain barrier is accountable for restricting drugs entry at the tumor location and related biological challenges like endocytic degradation, short systemic circulation, and insufficient cellular penetration lead to tumor aggression and progression. The above stated challenges can be better mitigated by small interfering RNAs (siRNA) by knockdown genes responsible for tumor progression and resistance. However, siRNA encounters with challenges like inefficient cellular transfection, short circulation time, endogenous degradation, and off-target effects. The novel functionalized nanocarrier approach in conjunction with biological and chemical modification offers an intriguing potential to address challenges associated with the naked siRNA and efficiently silence STAT3, coffilin-1, EGFR, VEGF, SMO, MGMT, HAO-1, GPX-4, TfR, LDLR and galectin-1 genes in GBM tumor. This review highlights the nanoengineered siRNA carriers, their recent advancements, future perspectives, and strategies to overcome the systemic siRNA delivery challenges for glioma treatment., Competing Interests: Declaration of competing interest The authors do not declare any conflict of interest among themselves., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Targeted therapies enhance the efficacy of tumour screening and management while lowering side effects. Multiple tumours, including liver cancer, exhibit elevated levels of folate receptor expression. This research attempted to develop surface-functionalised bosutinib cubosomes against hepatocellular carcinoma. The novelty of this work is the anti-hepatic action of bosutinib (BST) and folic acid-modified bosutinib cubosomes (BSTMF) established through proto-oncogene tyrosine-protein kinase (SrC)/ focal adhesion kinase(FAK), reactive oxygen species (ROS), mitochondrial membrane potential (MMP), and cell cytotoxicity. Later, the in-vivo pharmacokinetics of BSTMF were determined for the first time. The strong affinity of folic acid (FA) for folate receptors allows BSTMF to enter cells via FA receptor-mediated endocytosis. The particle size of the prepared BSTMF was 188.5 ± 2.25 nm, and its zeta potential was -20.19 ± 2.01 mV, an encapsulation efficiency of 90.31 ± 3.15 %, and a drug release rate of 76.70 ± 2.10 % for 48 h. The surface architecture of BSTMF was identified using transmission electron microscopy (TEM) and Atomic force microscopy (AFM). Cell-line studies demonstrated that BSTMF substantially lowered the viability of Hep G2 cells compared to BST and bosutinib-loaded cubosomes (BSTF). BSTMF demonstrated an elevated BST concentration in tumour tissue than in other organs and also displayed superior pharmacokinetics, implying that they hold potential against hepatic cancers. This is the first study to show that BSTMF may be effective against liver cancer by targeting folate receptors and triggering SrC/FAK-dependent apoptotic pathways. Multiple parameters demonstrated that BSTMF enhanced anticancer targeting, therapeutic efficacy, and safety in NDEA-induced hepatocellular carcinoma., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Raquibun Nisha reports financial support was provided by Babasaheb Bhimrao Ambedkar University. Raquibun Nisha reports a relationship with Babasaheb Bhimrao Ambedkar University that includes: funding grants. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Orally targeted delivery systems have attracted ample interest in colorectal cancer management. In this investigation, we developed Inositol hexaphosphate (IHP) loaded Tripolyphosphate (Tr) crosslinked Pectin (Pe) Chitosan (Ch) nanoparticles (IHP@Tr*Pe-Ch-NPs) and modified them with l-Carnitine (CE) (CE-IHP@Tr*Pe-Ch-NPs) to improve uptake in colon cells. The formulated CE-IHP@Tr*Pe-Ch-NPs displayed a monodisperse distribution with 219.3 ± 5.5 nm diameter and 30.17 mV surface charge. Cell-line studies revealed that CE-IHP@Tr*Pe-Ch-NPs exhibited excellent biocompatibility in J774.2 and decreased cell viability in DLD-1, HT-29, and MCF7 cell lines. More cell internalization was seen in HT-29 and MCF7 due to overexpression of the OCTN2 and ATB 0,+ transporter (CE transporters) compared to DLD-1. The cell cycle profile, reactive oxygen species, apoptosis, and mitochondrial membrane potential assays were performed to explore the chemo-preventive mechanism of CE-IHP@Tr*Pe-Ch-NPs. Moreover, the in-silico docking studies revealed enhanced interactive behavior of CE-IHP@Tr*Pe-Ch-NPs, thereby proving their targeting ability. All the findings suggested that CE-IHP@Tr*Pe-Ch-NPs could be a promising drug delivery approach for colon cancer targeting., Competing Interests: Declaration of competing interest All the authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Doxorubicin is a powerful chemotherapy medicine that is frequently used to treat cancer, but because of its extremely destructive side effects on other healthy cells, its applications have been severely constrained. With the aim of using lower therapeutic doses of doxorubicin while maintaining the same anti-cancerous activity as those of higher doses, the present study designs nano-encapsulation of doxorubicin by acrylamide grafted melanin as core and acrylic acid grafted flax seed gum as shell (DOX@AAM-g-ML/AA-g-FSG-NPs) for studies in-vivo and in-vitro anticancer activity. For biological studies, the cytotoxicity of DOX@AAM-g-ML/AA-g-FSG-NPs was examined on a cancerous human cell line (HCT-15) and it was observed that DOX@AAM-g-ML/AA-g-FSG-NPs exhibited very high toxicity towards HCT-15. In-vivo investigation in colon cancer-inflicted rat model also showed that DOX@AAM-g-ML/AA-g-FSG-NPs showed better anticancer activity against cancerous cells as compared to free doxorubicin. The drug release behavior of DOX@GML-GFS-NPs was studied at several pH and maximum drug release (95 %) was recorded at pH -7.2, and kinetic data of drug release was follows the Higuchi (R 2  = 0.9706) kinetic model. Our study is focussed on reducing the side effects of doxorubicin by its nano-encapsulation in acrylamide grafted melanin as core and acrylic acid grafted flax seed gum that will also enhance its efficiency., Competing Interests: Declaration of competing interest Author “Prof. Patit Paban Kundu” certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript., (Copyright © 2023. Published by Elsevier B.V.)

An association between the loss of skeletal muscle mass and obesity in the geriatric population has been identified as a disease known as sarcopenic obesity. Therefore, therapeutic/preventive interventions are needed to ameliorate sarcopenia. The present study investigates the effect of azilsartan (AZL) on skeletal muscle loss in High-Fat Diet (HFD)-induced sarcopenic obese (SO) rats. Four- and fourteen-months male Sprague Dawley rats were used and randomized in control and azilsartan treatment. 14 months animals were fed with HFD for four months and labeled as HFD-fed SO rats. Young & old rats received 0.5% carboxymethyl cellulose as a vehicle/AZL (8 mg/kg, per oral) treatment for six weeks. Grip strength and body composition analysis were performed after the last dose of AZL. Serum and gastrocnemius (GN)muscles were collected after animal sacrifice. AZL treatment significantly increased lean muscle mass, grip strength, myofibrillar protein, and antioxidant (superoxide dismutase & nitric oxide) levels in SO rats. AZL also restored the muscle biomarkers (creatine kinase, myostatin & testosterone), and insulin levels. AZL improves cellular, and ultracellular muscle structure and prevents type I to type II myofiber transitions in SO rats. Further, immunohistochemistry results showed increased expressions of pAkt and reduced expression of MuRF-1 and TNF-α exhibiting that AZL intervention could decrease protein degradation in SO rats. In conclusion, present results showed that AZL significantly increased lean mass, and restored muscle biomarkers, and muscle architecture. Taken together, the aforementioned findings suggest that azilsartan could be a possible therapeutic approach to reduce muscle wasting in sarcopenic obesity., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The purpose of this study was to evaluate the drug delivery and therapeutic potential of berberine (Br) loaded nanoformulation in rheumatoid arthritis (RA)-induced animal model. The Br-loaded NLCs (nanostructured lipid carriers) were prepared employing melt-emulsification process, and optimised through Box-Behnken design. The prepared NLCs were assessed for in-vitro and in-vivo evaluations. The optimised NLCs exhibited a mean diameter of 180.2 ± 0.31 nm with 88.32 ± 2.43% entrapment efficiency. An enhanced anti-arthritic activity with reduced arthritic scores to 0.66 ± 0.51, reduction in ankle diameter to 5.80 ± 0.27 mm, decline in paw withdrawal timing, and improvements in walking behaviour were observed in the Br-NLCs treated group. The radiographic images revealed a reduction in bone and cartilage deformation. The Br-NLCs showed promising results in the management of RA disease, can be developed as an efficient delivery system at commercial levels, and may be explored for clinical application after suitable experiments in the future.

Some breast cancers are caused by hormonal imbalances, such as estrogen and progesterone. These hormones play a function in directing the growth of cancer cells. The hormone receptors in hormone receptor-positive breast cancer lead breast cells to proliferate out of control. Cancer therapy such as hormonal, targeted, radiation is still unsatisfactory because of these challenges namely multiple drug resistance (MDR), off-targeting, severe adverse effects. A novel aromatase inhibitor exemestane (Exe) exhibits promising therapy in breast cancer. This study aims to develop and optimize Exe-loaded lipid nanocapsules (LNCs) by using DSPC, PF68 and olive oil as lipid, surfactant and oil phase, respectively and to characterize the same. The prepared nanocapsules were investigated via in vitro cell culture and in vivo animal models. The LNCs exhibited cytotoxicity in MCF-7 cell lines and enhanced anti-cancer activity and reduced cardiotoxicity in DMBA-induced animal model when compared to the drug. Additionally, in vivo pharmacokinetics revealed a 4.2-fold increased oral bioavailability when compared with Exe suspension. This study demonstrated that oral administration of Exe-loaded LNCs holds promise for the antiestrogenic activity of exemestane in breast cancer.

Polysaccharide-based nanoparticles (NPs) such as pectin/ chitosan (PN/CN) had always been of greatest interest because of their excellent solubility, biocompatibility, and higher suitability for oral drug delivery. This study employed blending-crosslinking of polymers (PN&CN) followed by emulsification-solvent evaporation to prepare and compare two sets of PEGylated NPs to deliver phytic acid (IP6) to colon orally as it has potential to manage colon cancer but fails to reach colon when ingested in pure form. The first set was crosslinked with Glutaraldehyde (GE) (GE*PN-CN-NPs) while the second set was crosslinked with sodium tripolyphosphate (TPP) (TPP*PN-CN-NPs). IP6-loaded-GE/TPP*PN-CN-NPs were optimized using a central composite design. Developed TPP*PN-CN-NPs had a smaller size (210.6 ± 7.93 nm) than GE*PN-CN-NPs (557.2 ± 5.027 nm). Prepared NPs showed <12% IP6 release at pH 1.2 whereas >80% release was observed at pH 7.4. Further, NPs were explored for cytocompatibility in J774.2 cell lines, cytotoxicity, and cellular uptake in HT-29 and DLD-1 cell lines. While exhibiting substantial cytotoxicity and cellular uptake in HT-29 and DLD-1, the NPs were deemedsafe in J774.2. The PEGylated-TPP*PN-CN-NPs showed time-dependent uptake in J774.2 cell lines. Conclusively, the employed NP development method successfully delivered IP6 to colon and may also open avenues for the oral delivery of other drugs to colon., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Natural killer/T-cell lymphoma (NKTL) is a rare type of aggressive and heterogeneous non-Hodgkin's lymphoma (NHL) with a poor prognosis and limited therapeutic options. Therefore, there is an urgent need to exploit potential novel therapeutic targets for the treatment of NKTL. Histone deacetylase (HDAC) inhibitor chidamide was recently approved for treating relapsed/refractory peripheral T-cell lymphoma (PTCL) patients. However, its therapeutic efficacy in NKTL remains unclear., Methods: We performed a phase II clinical trial to evaluate the efficacy of chidamide in 28 relapsed/refractory NKTL patients. Integrative transcriptomic, chromatin profiling analysis and functional studies were performed to identify potential predictive biomarkers and unravel the mechanisms of resistance to chidamide. Immunohistochemistry (IHC) was used to validate the predictive biomarkers in tumors from the clinical trial., Results: We demonstrated that chidamide is effective in treating relapsed/refractory NKTL patients, achieving an overall response and complete response rate of 39 and 18%, respectively. In vitro studies showed that hyperactivity of JAK-STAT signaling in NKTL cell lines was associated with the resistance to chidamide. Mechanistically, our results revealed that aberrant JAK-STAT signaling remodels the chromatin and confers resistance to chidamide. Subsequently, inhibition of JAK-STAT activity could overcome resistance to chidamide by reprogramming the chromatin from a resistant to sensitive state, leading to synergistic anti-tumor effect in vitro and in vivo. More importantly, our clinical data demonstrated that combinatorial therapy with chidamide and JAK inhibitor ruxolitinib is effective against chidamide-resistant NKTL. In addition, we identified TNFRSF8 (CD30), a downstream target of the JAK-STAT pathway, as a potential biomarker that could predict NKTL sensitivity to chidamide., Conclusions: Our study suggests that chidamide, in combination with JAK-STAT inhibitors, can be a novel targeted therapy in the standard of care for NKTL., Trial Registration: ClinicalTrials.gov, NCT02878278. Registered 25 August 2016, https://clinicaltrials.gov/ct2/show/NCT02878278., (© 2023. The Author(s).)

Rheumatoid arthritis (RA) is a joint ailment with multi-factorial immune-mediated degenerative pathogenesis, including genetic and environmental defects. Resistance to disease-modifying anti-rheumatic drugs (DMARDs) happens due to excessive drug efflux over time, rendering the concentration insufficient to elicit a response. Thymoquinone (TQ) is a quinone-based phenolic compound with antioxidant and anti-inflammatory activities that downregulate numerous pro-inflammatory cytokines. However, its pharmaceutical importance and therapeutic utility are underexplored due to intrinsic physicochemical characteristics such as inadequate biological stability, short half-life, low hydrophilicity, and less systemic availability. Tamanu oil-stabilised nanostructured lipid carriers (TQ-NLCs) were prepared and optimised using Box-Behnken design (BBD) with the size of 153.9 ± 0.52 nm and surface charge of -30.71 mV. The % entrapment efficiency and drug content were found to be 84.6 ± 0.50% and 14.75 ± 0.52%, respectively. Furthermore, the TQ-loaded NLCs (TQ-NLCs) assayed for skin permeation for transdermal delivery which significantly (p < 0.05) increased skin enhancement ratio 14.6 times compared to the aqueous solution of TQ. Tamanu oil displayed the synergistic anti-inflammatory potential with TQ in comparison to pure TQ, as evidenced against carrageenan (CRG)-induced paw oedema model and Freund's adjuvant-induced arthritic model. The arthritic and X-ray scores significantly (p < 0.05) reduced in TQ-NLCs and standard formulation-treated groups. Moreover, serum pro-inflammatory marker TNF-α and IL-6 levels were also significantly (p < 0.05) reduced in TQ-NLCs gel-treated group compared to the arthritic control group., (© 2022. Controlled Release Society.)

Infected wounds that do not heal are a worldwide problem that is worsening, with more people dying and more money being spent on care. For any disease to be managed effectively, its root cause must be addressed. Effective wound care becomes a bigger problem when various traditional wound healing methods and products may not only fail to promote good healing. Still, it may also hinder the healing process, causing wounds to stay open longer. Progress in tissue regeneration has led to developing three-dimensional scaffolds (3D) or constructs that can be leveraged to facilitate cell growth and regeneration while preventing infection and accelerating wound healing. Tissue regeneration uses natural and fabricated biomaterials that encourage the growth of tissues or organs. Even though the clinical need is urgent, the demand for polymer-based therapeutic techniques for skin tissue abnormalities has grown quickly. Hydrogel scaffolds have become one of the most imperative 3D cross-linked scaffolds for tissue regeneration because they can hold water perfectly and are porous, biocompatible, biodegradable, and biomimetic. For damaged organs or tissues to heal well, the porosity topography of the natural extracellular matrix (ECM) should be imitated. This review details the scaffolds that heal wounds and helps skin tissue to develop. After a brief overview of the bioactive and drug-loaded polymeric hydrogels, the discussion moves on to how the scaffolds are made and what they are made of. It highlights the present uses of in vitro and in-vivo employed biomimetic scaffolds. The prospects of how well bioactiveloaded hydrogels heal wounds and how nanotechnology assists in healing and regeneration have been discussed., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Limited targeted therapies are available for triple-negative breast cancer (TNBC). Thus, the current research focused on developing a targeted protein nanoparticle for TNBC. First, the doxorubicin hydrochloride (Dox)-loaded genipin-crosslinked whey protein nanoparticles (WD) were prepared and optimised by the QbD method using BBD. The hydrodynamic diameter of WD was found to be 364.38 ± 49.23 nm, zeta potential -27.59 ± 1.038 mV, entrapment 63.03 ± 3.625% and Dox loading was found to be 1.419 ± 0.422%. The drug recovery after 18 months of storage was 69%. Then, it was incubated with NAC to obtain modified WD (CyWD). WD followed first-order release kinetics, whereas CyWD followed the Higuchi model. Hemagglutination and hemolysis were not found qualitatively in WD and CyWD. Upon injecting the nanoformulations to 4T1-induced mice, the highest efficacy was found to be in CyWD followed by WD and Dox injection. Upon histopathological observance, it was found that the CyWD group gave the most significant damage to the 4T1 tumour tissue. Thus, NAC-modified protein nanoparticles carrying chemotherapeutic agents can be an excellent targeted therapeutic system against TNBC., (© 2022. Controlled Release Society.)

Aim: To assess the targeting ability of hybrid nanosystems functionalized with folate. It also aimed to reduce stomach intolerance by substituting the oral route for parenteral delivery. Method: The nanosystems, prepared by nanoprecipitation technique, utilized a one-step method to prepare nanoparticles followed by surface functionalization through adsorption. The prepared nanosystems underwent physical characterization, in vitro and in vivo evaluations. Result: The nanosystems were effective in targeting the alveolar macrophages. Ethionamide was released from the formulation over 5 days. Fourier-transform infrared results proved the structural characteristics, and the positive charge further improved the targeting efficacy on the functionalized system. Conclusion: The hybrid formulation improved the release characteristics. Reduction in dosing frequency due to prolonged release improves compliance with the dosage regimen.

This study was designed to create surface-functionalized bosutinib liposomes that could be used for the management of estrogen-positive cancers. The novelty of this work was the anti-cancer activity of bosutinib-loaded liposomes (Bos-LPs) in estrogen-positive cancer via estrogen response elements, responsible for the malignancy of cancer cells. Biotin effectively delivers active moiety to tumor tissues because it interacts with the biotin receptor and operates through the Sodium-dependent multivitamin transporters (SMVT) transporter. The prepared liposomes had a 257.73 ± 4.50 nm particle size, - 28.07 ± 5.81 mV zeta potential, 87.78 ± 1.16 % encapsulation efficiency and 85.56 ± 0.95 % drug release for 48 h. The surface architecture of biotin-modified bosutinib-loaded liposomes (b-Bos-LPs) was confirmed using scanning electron and transmission electron microscopies. In-vitro experiments revealed that b-Bos-LPs outperformed Bos and Bos-LPs in terms of significantly reduced cell viability in MCF-7 cells. According to biodistribution and pharmacokinetic studies, b-Bos-LPs have a higher Bos concentration in tumor tissues as compared to the other organs and also possess better pharmacokinetic activity, indicating that they can be used to treat carcinogen-induced estrogen-positive cancers. This is the first study to show that b-Bos-LPs can display activity against estrogen-positive cancer via biotin targeting. As evidenced by various parameters, b-Bos-LPs showed improved anticancer targeting, therapeutic safety and efficacy in carcinogen-induced estrogen-positive cancer. The receptor protein estrogen, which is primarily responsible for this cancer was downregulated by b-Bos-LPs in an immunoblotting assay. The results showed that biotinylated distearoylphosphatidylcholine (DSPC) augmented LPs loaded with Bosutinib can cause apoptosis in estrogen-positive breast cancer and be an effective way to treat estrogen-positive cancer., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Priya Singh reports financial support was provided by DST Inspire Fellowship. The authors report no conflicts of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

There is a curious case in Alveolar macrophages (AM), the frontline defence recruits that contain the spread of all intruding bacteria. In response to Mycobacterium tuberculosis (M.tb), AM either contain the spread or are modulated by M.tb to create a region for their replication. The M.tb containing granulomas so formed are organised structures with confined boundaries. The limited availability of drugs inside AM aid drug tolerance and poor therapeutic outcomes in diseases like tuberculosis. The present work proves the glycotargeting efficiency of levofloxacin (LVF) to AM. The optimised formulation developed displayed good safety with 2% hemolysis and a viability of 61.14% on J774A.1 cells. The physicochemical characterisations such as Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) proved that carubinose linkage was accomplished and LVF is entrapped inside carubinose-linked hybrid formulation (CHF) and hybrid formulation (HF) in amorphous form. The transmission electron microscopy (TEM) images revealed a core-shell structure of HF. The particle size of 471.5 nm estimated through dynamic light scattering (DLS) is enough to achieve active and passive targeting to AM. The nanoparticle tracking analysis (NTA) data revealed that the diluted samples were free from aggregates. Fluorescence-activated cell sorting (FACS) data exhibited excellent uptake via CHF (15 times) and HF(3 times) with reference to plain fluorescein isothiocyanate (FITC). The pharmacokinetic studies revealed that CHF and HF release the entrapped moiety LVF in a controlled manner over 72 h. The stability studies indicated that the modified formulation remains stable over 6 months at 5 ± 3℃. Hence, hybrid systems can be efficiently modified via carubinose to target AM via the parenteral route., (© 2021. Controlled Release Society.)

This study aimed at the development of hyaluronic acid-functionalised imatinib mesylate cubosomes (HA-IM-CBs) that might be useful in CD44 targeting against hepatic cancer. The HA-IM-CBs had a 130.7 ± 2.92 nm particle size, -31.40 ± 2.76 mV zeta potential, and 76.14 ± 2.69% release. The architecture of HA-IM-CBs was confirmed using HR-TEM and AFM. When compared to plain IM and IM-CBs, in vitro experiments revealed that HA-IM-CBs outperformed by significantly reducing cell viability. DAPI staining and ROS corroborated the apoptotic effects. Biodistribution and Pharmacokinetics studies showedthat HA-IM-CBs exhibit a higher drug concentration in tumour tissue and better pharmacokinetic activity. This is the first study to show that HA-IM-CBs had CD44 targeting activity against HCC. CD44 regulates apoptosis via Bcl-2 family proteins and caspases, which interact with HA. Higher levels of e-NOS, BAD, BAX, and Cyt C and lower expressions of Bcl-xl, i-NOS, and Bcl-2 demonstrated the anti-HCC potential of HA-IM-CBs in qrt-PCR investigations. The remarkable therapeutic potential of HA-IM-CBs began with substantial stimulation of CD44 regulated caspase-mediated mitochondrial apoptotic pathway, accountable for their anti-HCC activity. The perturbed metabolites are restored to acceptable levels as indicated by metabolomic studies ( 1 H NMR). Interestingly, the antineoplastic effect of HA-IM-CBs was proven to be potentially valuable against HCC., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Present study is aimed at transdermal delivery of colchicine-loaded chitosan nanoparticles. The nanoformulations were prepared utilising spontaneous emulsification method and optimised through 2 3 factorial designs. The optimised formulation (CHNP-OPT) displayed an average particle size of 294 ± 3.75 nm, entrapment efficiency 92.89 ± 1.1% and drug content 83.45 ± 2.5%, respectively. In vitro release study demonstrated 89.34 ± 2.90% release over a period of 24 h. Further, CHNP-OPT incorporated into HPMC-E4M (hydroxypropyl methylcellulose) to form transdermal gel. CHNP gel displayed 74.65 ± 1.90% permeation and stability over a period of 90 days. The anti-gout potential of CHNP gel formulation was evaluated in vivo against monosodium urate (MSU) crystal-induced gout in animal model. There was significant reduction in uric acid level, during MSU administration, when compared with the conventional gel of colchicine. The enhanced therapeutic potential was witnessed through X-ray. The study revealed that colchicine-loaded CHNP gel proved their supremacy over plain colchicine and can be an efficient delivery system for gout treatment.

Colorectal cancer is one of the most common cancers worldwide, accounting for an annual estimated 1.8 million incident cases. With the increasing number of colonoscopies being performed, colorectal biopsies make up a large proportion of any histopathology laboratory workload. We trained and validated a unique artificial intelligence (AI) deep learning model as an assistive tool to screen for colonic malignancies in colorectal specimens, in order to improve cancer detection and classification; enabling busy pathologists to focus on higher order decision-making tasks. The study cohort consists of Whole Slide Images (WSI) obtained from 294 colorectal specimens. Qritive's unique composite algorithm comprises both a deep learning model based on a Faster Region Based Convolutional Neural Network (Faster-RCNN) architecture for instance segmentation with a ResNet-101 feature extraction backbone that provides glandular segmentation, and a classical machine learning classifier. The initial training used pathologists' annotations on a cohort of 66,191 image tiles extracted from 39 WSIs. A subsequent application of a classical machine learning-based slide classifier sorted the WSIs into 'low risk' (benign, inflammation) and 'high risk' (dysplasia, malignancy) categories. We further trained the composite AI-model's performance on a larger cohort of 105 resections WSIs and then validated our findings on a cohort of 150 biopsies WSIs against the classifications of two independently blinded pathologists. We evaluated the area under the receiver-operator characteristic curve (AUC) and other performance metrics. The AI model achieved an AUC of 0.917 in the validation cohort, with excellent sensitivity (97.4%) in detection of high risk features of dysplasia and malignancy. We demonstrate an unique composite AI-model incorporating both a glandular segmentation deep learning model and a classical machine learning classifier, with excellent sensitivity in picking up high risk colorectal features. As such, AI plays a role as a potential screening tool in assisting busy pathologists by outlining the dysplastic and malignant glands., (© 2022. The Author(s).)

Nanoparticles (NPs) as nanocarriers have emerged as novel and promising theranostic agents. The term theranostics revealed the properties of NPs capable of diagnosing the disease at an early stage and/or treating the disease. Such NPs are usually developed employing a surface engineering approach. The theranostic agents comprise NPs loaded with a drug/diagnostic agent that delivers it precisely to the target site. Theranostics is a field with promising results in enhancing therapeutic efficacy facilitated through higher payload at the targeted tissue, reduced dose, and dose-dependent side effects. However, controversies in terms of toxicity and size-dependent properties have often surfaced for NPs. Thus, a stringent in-vitro and in-vivo evaluation is required to develop safe and non-toxic NPs as theranostic agents. The review also focuses on the various entry points of NPs in the human system and their outcomes, including toxicity. It elaborates the evaluation criteria to ensure the safe use of NPs for diagnostic and therapeutic purposes., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Aim: Felodipine (FDP), an antihypertensive drug possesses low water solubility and extensive first-pass metabolism leading to poor bioavailability. This impelled us to improve its solubility, bioavailability, and pharmacodynamic properties through the Nanocrystal (NC) approach., Methods: FDP-NC were prepared with Poloxamer F125 (PXM) by the antisolvent precipitation method. The experimental setup aimed at fine-tuning polymer concentration, the proportion of antisolvent to solvent, and the duration of ultrasonication for NC formulation., Results: Optimized formulation was characterized for particle size, solubility, and PDI. Particle reduction of 74.96 times was achieved with a 9X solubility enhancement as equated to pure FDP. The morphology of NC was found to be crystalline through scanning electron microscopy observation. The formation of the crystal lattice in FDP-NC was further substantiated by the XRD and DSC results. Lowering of the heat of fusion of FDP-NC is a clear indication of size reduction. The stability studies showed no substantial change in physical parameters of the FDP-NC as assessed by particle size, zeta potential, and drug content., Conclusion: The crystalline nature and improved solubility of FDP-NC improve the dissolution profile and pharmacodynamic data. The stability study data ensure that FDP-NC can be safely stored at 25°C. It is revealed that FDP-NC had a better release profile and improved pharmacodynamic effects as evident from better control over heart rate than FDP., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

β-sitosterol (BS), a phytosterol, exhibits ameliorative effects on hepatocellular carcinoma (HCC) due to its antioxidant activities. However, its poor aqueous solubility and negotiated bioavailability and short elimination half-life is a huge limitation for its therapeutic applications. To overcome these two shortcomings, BS-loaded niosomes were made to via , film hydration method and process parameters were optimized using a three-factor Box-Behnken design. The optimized formulation (BSF) was further surface-modified with polyethylene glycol (PEG). The resulting niosomes (BSMF) have spherical shapes, particle sizes, 219.6 ± 1.98 nm with polydispersity index (PDI) and zeta potential of 0.078 ± 0.04 and -19.54 ± 0.19 mV, respectively. The drug loading, entrapment efficiency, and drug release at 24 h of the BSMF were found to be 16.72 ± 0.09%, 78.04 ± 0.92%, and 75.10 ± 3.06%, respectively. Moreover, BSMF showed significantly greater cytotoxic potentials on Hep G2 cells with an enhanced cellular uptake relative to pure BS and BSF. The BSMF also displayed potentially improved curative property of HCC in albino wistar rat. Thus, the BSMF could be one of the promising therapeutic modalities for HCC treatment in terms of targeting potential resulting in enhanced therapeutic efficacy.

The present work aims to synthesize the pH-sensitive crosslinked guar gum-g-poly(acrylic acid-co-acrylonitrile) [guar-g-(AA-co-ACN)] via microwave-assisted technique for the sustained release of thymoquinone. The synthesized material [guar-g-(AA-co-ACN)] was optimized by varying synthetic parameters viz. monomer concentration, reaction time, and microwave power to obtain the maximum yield of the crosslinked guar gum grafted product as well as maximum encapsulation of thymoquinone. The synthesized material [guar-g-poly(AA-co-ACN)] was characterized by FT-IR, SEM, XRD, NMR, zeta potential, and thermal techniques. This synthesized material was used to encapsulate thymoquinone (TQ) for effective nanotherapeutic delivery. In-vitro thymoquinone release behavior of guar-g-poly(AA-co-ACN) based nanoparticles (NpTGG) was investigated. The maximum thymoquinone release (78%) was achieved at pH 7.4 and time (6 h). The NpTGG also exhibited better antioxidant activity and hemocompatibility as compared to thymoquinone. Cytotoxicity of uar-g-(AA-co-ACN) and NpTGG was also evaluated against the human kidney VERO cell line and found to be nontoxic. Current research provides a cost-effective and green approach for the synthesis of guar-g-(AA-co-ACN) and NpTGG for sustained release of thymoquinone., (Copyright © 2021. Published by Elsevier B.V.)

Cancer causes a considerable amount of mortality in the world, while arthritis is an immunological dysregulation with multifactorial pathogenesis including genetic and environmental defects. Both conditions have inflammation as a part of their pathogenesis. Resistance to anticancer and disease-modifying antirheumatic drugs (DMARDs) happens frequently through the generation of energy-dependent transporters, which lead to the expulsion of cellular drug contents. Thymoquinone (TQ) is a bioactive molecule with anticancer as well as anti-inflammatory activities via the downregulation of several chemokines and cytokines. Nevertheless, the pharmacological importance and therapeutic feasibility of thymoquinone are underutilized due to intrinsic pharmacokinetics, including short half-life, inadequate biological stability, poor aqueous solubility, and low bioavailability. Owing to these pharmacokinetic limitations of TQ, nanoformulations have gained remarkable attention in recent years. Therefore, this compilation intends to critically analyze recent advancements in rheumatoid arthritis and cancer delivery of TQ. This literature search revealed that nanocarriers exhibit potential results in achieving targetability, maximizing drug internalization, as well as enhancing the anti-inflammatory and anticancer efficacy of TQ. Additionally, TQ-NPs (thymoquinone nanoparticles) as a therapeutic payload modulated autophagy as well as enhanced the potential of other drugs when given in combination. Moreover, nanoformulations improved pharmacokinetics, drug deposition, using EPR (enhanced permeability and retention) and receptor-mediated delivery, and enhanced anti-inflammatory and anticancer properties. TQ's potential to reduce metal toxicity, its clinical trials and patents have also been discussed.

Hepatocellular carcinoma (HCC) is a major cause of concern as it has substantial morbidity associated with it. Previous reports have ascertained the antiproliferative activity of imatinib mesylate (IMS) against diverse types of carcinomas, but limited bioavailability has also been reported. The present study envisaged optimized IMS-loaded lactoferrin (LF)-modified PEGylated liquid crystalline nanoparticles (IMS-LF-LCNPs) for effective therapy of IMS to HCC via asialoglycoprotein receptor (ASGPR) targeting. Results displayed that IMS-LF-LCNPs presented an optimum particle size of 120.40 ± 2.75 nm, a zeta potential of +12.5 ± 0.23 mV, and 73.94 ± 2.69% release. High-resolution transmission electron microscopy and atomic force microscopy were used to confirm the surface architecture of IMS-LF-LCNPs. The results of cytotoxicity and 4,6-diamidino-2-phenylindole revealed that IMS-LF-LCNPs had the highest growth inhibition and significant apoptotic effects. Pharmacokinetics and biodistribution studies showed that IMS-LF-LCNPs have superior pharmacokinetic performance and targeted delivery compared to IMS-LCNPs and plain IMS, which was attributed to the targeting action of LF that targets the ASGPR in hepatic cells. Next, our in vivo experiment established that the HCC environment existed due to suppression of BAX, cyt c , BAD, e-NOS, and caspase (3 and 9) genes, which thus owed upstream expression of Bcl-xl, iNOS, and Bcl-2 genes. The excellent therapeutic potential of IMS-LF-LCNPs began the significant stimulation of caspase-mediated apoptotic signals accountable for its anti-HCC prospect. 1 H nuclear magnetic resonance (serum) metabolomics revealed that IMS-LF-LCNPs are capable of regulating the disturbed levels of metabolites linked to HCC triggered through N -nitrosodiethylamine. Therefore, IMS-LF-LCNPs are a potentially effective formulation against HCC.

Background: Parkinsonism has a toxic cascade of neurodegeneration, with akinesia as a major manifestation. Some antioxidants have shown promise against the disease. Astaxanthin is a powerful antioxidant, demonstrates free radical scavenging, and is also a potential neuroprotective agent., Objective: The objective of this study was to formulate astaxanthin-laden nanostructured lipid carriers based thermoreversible gel for better neuronal uptake and better neuronal efficacy., Methods: The method for fabricating astaxanthin-nanostructured lipid carriers (ATX-NLC) was melt-emulsification, and these were optimized using factorial design and further evaluated for diverse parameters. Neurotoxicity was induced in rats by haloperidol. The treated and non-treated rats were then witnessed for their behaviour. TBARs and GSH levels were also determined. Pharmacokinetics was studied via HPLC., Results: The average particle size (by DLS), entrapment efficiency and zeta potential of optimized ATX-NLC were 225.6 ± 3.04 nm, 65.91 ± 1.22% and -52.64 mV, respectively. Astaxanthin release (after 24 h in simulated nasal fluid) from optimized ATX-NLC was 92.5 ± 5.42%. Its thermoreversible nasal gel (ATX-NLC in-situ gel) was prepared using poloxamer-127. The obtained gel showed in-vivo betterment in the behaviour of animals when studied using the rotarod and akinesia test. Pharmacokinetic studies showed better availability of astaxanthin in the brain on the rats treated with ATX-NLC in-situ gel as compared to those treated with ATX-in-situ gel., Conclusion: Astaxanthin-loaded lipidic nanoparticulate gel can be a hopeful adjuvant therapy for Parkinsonism and holds scope for future studies., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Naringenin (NAR) is a flavonoid found in citrus fruits such as grapes and oranges. Recently, NAR has demonstrated its potential in inhibition of photoaging. The aim of the present study was to investigate the efficacy of sericin (SR) gel loaded with NAR microemulsion (ME) to inhibit UVB-induced photoaging and prevention of epidermoid carcinoma in animal model. NAR -ME was prepared and optimized through Box-Behnken design. The optimized ME was loaded into sericin (SR) gel. The formulations were subjected to various in vitro, in vivo and cytotoxicity studies over A431 cell lines. The optimized ME revealed a globule size of 249.05 ± 3.78 nm, 6.7 ± 0.5 pH and 73.1 ± 2.11% release over a period of 24 h respectively. Cytotoxicity studies revealed a depression in IC 50 value in NAR -ME (65.11 ± 1.54 μg/ml) when compared with NAR (118.1 ± 2.09 μg/ml). The NAR-ME-SR gel displayed enhanced therapeutic potential when compared with plain NAR, in terms of augmented antiproliferative activity. Graphical abstract.