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Mahmood Barani,1 Enrico Sangiovanni,2 Marco Angarano,2 Mohammad Amin Rajizadeh,3 Mehrnaz Mehrabani,4 Stefano Piazza,2 Hosahalli Veerabhadrappa Gangadharappa,5 Abbas Pardakhty,6 Mehrzad Mehrbani,7 Mario Dell’Agli,2 Mohammad Hadi Nematollahi8 1Medical Mycology and Bacteriology Research Center, Kerman University of Medical Sciences, Kerman, 76169-13555, Iran; 2Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, 20133, Italy; 3Student Research Committee, Kerman University of Medical Sciences, Kerman, Iran; 4Physiology Research Center, Kerman University of Medical Sciences, Kerman, Iran; 5Department of Pharmaceutics, JSS College of Pharmacy, JSS Academy of Higher Education and Research, Mysuru, India; 6Pharmaceutics Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran; 7Department of Traditional Medicine, Faculty of Traditional Medicine, Kerman University of Medical Sciences, Kerman, Iran; 8Herbal and Traditional Medicines Research Center, Kerman University of Medical Sciences, Kerman, IranCorrespondence: Mario Dell’AgliDepartment of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Via Balzaretti 9, Milan, 20133, ItalyEmail mario.dellagli@unimi.itMohammad Hadi NematollahiDepartment of Clinical Biochemistry, Kerman University of Medical Sciences, Kerman, IranEmail mh.nematollahi@yahoo.comAbstract: Nowadays, medicinal herbs and their phytochemicals have emerged as a great therapeutic option for many disorders. However, poor bioavailability and selectivity might limit their clinical application. Therefore, bioavailability is considered a notable challenge to improve bio-efficacy in transporting dietary phytochemicals. Different methods have been proposed for generating effective carrier systems to enhance the bioavailability of phytochemicals. Among them, nano-vesicles have been introduced as promising candidates for the delivery of insoluble phytochemicals. Due to the easy preparation of the bilayer vesicles and their adaptability, they have been widely used and approved by the scientific literature. The first part of the review is focused on introducing phytosome technology as well as its applications, with emphasis on principles of formulations and characterization. The second part provides a wide overview of biological activities of commercial and non-commercial phytosomes, divided by systems and related pathologies. These results confirm the greater effectiveness of phytosomes, both in terms of biological activity or reduced dosage, highlighting curcumin and silymarin as the most formulated compounds. Finally, we describe the promising clinical and experimental findings regarding the applications of phytosomes. The conclusion of this study encourages the researchers to transfer their knowledge from laboratories to market, for a further development of these products.Keywords: phytochemical, nanomedicine, phytosome, delivery, vesicle, disease

Afrasim Moin,1 Hosahalli V Gangadharappa,2 Mohd Adnan,3 Syed M Rizvi,1 Syed A Ashraf,4 Mitesh Patel,5 Amr S Abu Lila,1,6 Ahmed N Allam7 1Department of Pharmaceutics, College of Pharmacy, University of Hail, Hail, Saudi Arabia; 2Department of Pharmaceutics, JSS College of Pharmacy, JSS Academy of Higher Education and Research, Mysuru, India; 3Department of Biology, College of Science, University of Hail, Hail, Saudi Arabia; 4Department of Clinical Nutrition, College of Applied Medical Sciences, University of Hail, Hail, Saudi Arabia; 5Bapalal Vaidya Botanical Research Centre, Department of Biosciences, Veer Narmad South Gujarat University, Surat, Gujarat, India; 6Department of Pharmaceutics, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt; 7Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, Alexandria, EgyptCorrespondence: Ahmed N AllamDepartment of Pharmaceutics, Faculty of Pharmacy, Alexandria University, Alexandria 21521, EgyptTel +20 100 5422491Email ph.a.allam@gmail.comPurpose: The present work aimed at challenging the efficacy of natural gums, karaya and locust bean gum, as matrix-forming polymers for the formulation of sustained-release tablets of diltiazem, a model drug.Methods: Central design composite was adopted for the formulation and optimization of tablet formulations. The two gums have been selected as independent variables. The dependent factors chosen were the amount of drug released in 1st hour (Y1), amount of drug released after 12 h (Y2), diffusion exponent (Y3), and time for half of the total drug released (T50%) (Y4). Wet granulation approach was used for the formulation of tablets. FT-IR, DSC, in vitro dissolution, swelling-erosion investigations, SEM, and stability studies were carried out.Results and Discussion: It was evident that the release pattern from the prepared formulations was significantly influenced by the quantity of gum(s) in the tablet. FT-IR and DSC results confirm drug–polymer compatibility. Polynomial equations were used for the prediction of quantitative impact of independent factors at different levels on response variables. After ANOVA analysis, the significant factors were considered for constrained optimization to get the optimized formula. The optimized formula generated by the response surface methodology was evaluated both for in vitro and in vivo properties. The optimized formula and a sustained-release marketed product were subjected to in vivo studies in rabbits and the results of the t-test demonstrated insignificant variation in pharmacokinetic parameters among the two formulations, confirming that the prepared tablet showed sustained-release profile.Conclusion: The results indicated that karaya and locust bean gum can be effectively used to formulate sustained-release tablets.Keywords: locust bean gum, karaya gum, diltiazem hydrochloride, response surface methodology, sustained release

Background: Poorly water-soluble medicaments continue to be a challenging, however, significant class of herbal drugs for the management of an extensive range of ailments. Solid dispersion (SD) has emerged as one of the most effective formulation approaches to enhance the dissolution of poorly water-soluble herbal drugs. Formulation of solid dispersion is one of the most effective methods to enhance the aqueous solubility of highly lipophilic drugs which belong to BCS class II and IV. An amorphous form of the drug is more unstable and highly soluble in water and is attained by formulating solid dispersion. Purpose: This review explains various physicochemical properties, criteria for carrier selection, and causes of instability of solid dispersion to improve the therapeutic potential of poorly water-soluble herbal drugs. Methodology: To classify and explain some newer techniques used nowadays along with solid dispersion which could prevent recrystallization and precipitation of drug. Some herbal drugs with high therapeutic value and poor aqueous solubility were also enlisted which could be formulated in the form of solid dispersion to have better oral bioavailability. Results: The solid dispersions studies have revealed better performance for the dissolution which might be due to its alteration from crystalline to amorphous form in addition to the adherence of hydrophilic carriers to the surface of poorly water-soluble herbal drugs. These techniques will assist in the formation of a more stable solid dispersion. Conclusion: The application of solid dispersion technique in enhancing the aqueous solubility of poorly aqueous soluble herbal drugs should direct to the constant and enhanced bioavailability, leading to an enhanced therapeutic potential.

The clinical utility of raloxifene (RLX), a selective estrogen receptor modulator (SERM), has been compromised by severe side effects and unfavorable drug properties. To address these, a transferrin (Tf) conjugated graphene oxide nanoribbon (GONR) platform was tried for RLX. The stability of GONRs in biological media was improved by surface modification with 1, 2-Distearoyl-sn-glycero-3 phosphoethanolamine-Poly (ethylene glycol) (DSPE-PEG). The Tf molecule was covalently attached to DSPE-PEG (DPT) using EDC-NHS chemistry. The surface of GONR was then modified with DSPE-PEG (DP) or DPT and loaded with RLX (GDP-RLX and GDPT-RLX). The final formulations were characterized for drug loading and stability. The anticancer activities of pure RLX, GDP-RLX, and GDPT-RLX were evaluated and compared in all the in vitro and in vivo studies. In vitro cell line studies showed that GDPT-RLX have significantly high cytotoxicity, cellular uptake, apoptosis induction, G2/M phase arrest, anti-migration properties, and apoptotic protein expression, followed by GDP-RLX and RLX. Pharmacokinetics and tumor biodistribution were also found to be excellent with GDPT-RLX. The in vivo tumor therapy and tumor evaluation outcomes were also consistent with the in vitro data. The Tf conjugated GDPT-RLX represents a promising approach for targeted and sustained delivery of RLX with enhanced therapeutic efficacy., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: H.V. Gangadharappa reports financial support was provided by Indian Council of Medical Research, New Delhi, India. Asha P. Johnson reports financial support was provided by Indian Council of Medical Research, New Delhi, India. Asha P. Johnson, S. L. Jyothi and H.V. Gangadharappa has patent #An Indian patent application has been filed titled “Transferrin Conjugated Raloxifene loaded Graphene Oxide Nanoribbon Drug Delivery System.” (Application No. 202341053319 dated 09-August-2023) pending to JSS Academy of Higher Education & Research, Sri Shivarathreeshwara Nagara, Bannimantap, Mysuru 570,015, Karnataka, India and Indian Council of Medical Research, New Delhi, India. 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.)

In the realm of modern medicine, tissue engineering and regeneration stands as a beacon of hope, offering the promise of restoring form and function to damaged or diseased organs and tissues. Central to this revolutionary field are biological macromolecules-nature's own blueprints for regeneration. The growing interest in bio-derived macromolecules and their composites is driven by their environmentally friendly qualities, renewable nature, minimal carbon footprint, and widespread availability in our ecosystem. Capitalizing on these unique attributes, specific composites can be tailored and enhanced for potential utilization in the realm of tissue engineering (TE). This review predominantly concentrates on the present research trends involving TE scaffolds constructed from polysaccharides, proteins and glycosaminoglycans. It provides an overview of the prerequisites, production methods, and TE applications associated with a range of biological macromolecules. Furthermore, it tackles the challenges and opportunities arising from the adoption of these biomaterials in the field of TE. This review also presents a novel perspective on the development of functional biomaterials with broad applicability across various biomedical applications., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Prof. Umme Hani reports financial support was provided by Deanship of Scientific Research at King Khalid University, Saudi Arabia., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Pediatric brain tumors are the major cause of pediatric cancer mortality. They comprise a diverse group of tumors with different developmental origins, genetic profiles, therapeutic options, and outcomes. Despite many technological advancements, the treatment of pediatric brain cancers has remained a challenge. Treatment options for pediatric brain cancers have been ineffective due to non-specificity, inability to cross the blood-brain barrier, and causing off-target side effects. In recent years, nanotechnological advancements in the medical field have proven to be effective in curing challenging cancers like brain tumors. Moreover, nanoparticles have emerged successfully, particularly in carrying larger payloads, as well as their stability, safety, and efficacy monitoring. In the present review, we will emphasize pediatric brain cancers, barriers to treating these cancers, and novel treatment options.

In recent years, microneedles (MNs) have emerged as a promising alternative to traditional drug delivery systems in transdermal drug delivery. The use of MNs has demonstrated significant potential in improving patient acceptance and convenience while avoiding the invasiveness of traditional injections. Dissolving, solid, hollow, coated, and hydrogel microneedles are among the various types studied for drug delivery. Dissolving microneedles (DMNs), in particular, have gained attention for their safety, painlessness, patient convenience, and high delivery efficiency. This comprehensive review primarily focuses on different types of microneedles, fabrication methods, and materials used in fabrication of DMNs such as hyaluronic acid, chitosan, alginate, gelatin, collagen, silk fibroin, albumin, cellulose and starch, to list a few. The review also provides an exhaustive discussion on the applications of DMNs, including the delivery of vaccines, cosmetic agents, contraceptives, hormone and genes, and other therapeutic applications like for treating cancer, skin diseases, and diabetes, among others, are covered in this review. Additionally, this review highlights some of the DMN systems that are presently undergoing clinical trials. Finally, the review discusses current advances and trends in DMNs, as well as future prospective directions for this ground-breaking technology in drug delivery., 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.)

The aim of this study was to develop biotinylated chitosan (Bio-Chi) decorated multi-walled carbon nanotubes (MWCNTs) for breast cancer therapy with the tyrosine kinase inhibitor, neratinib (NT). For achieving such a purpose, carboxylic acid functionalized multiwalled carbon nanotubes (c-MWCNTs) were initially decorated non-covalently with biotin-chitosan (Bio-Chi) coating for achieving a dual targeting mode; pH-dependent release with chitosan and biotin-receptor mediated active targeting with biotin. Afterwards, Bio-Chi decorated c-MWCNTs were loaded with the tyrosine kinase inhibitor, neratinib (NT). The formulation was then characterized by dynamic light scattering, FTIR and EDX. The drug loading efficiency was estimated to be 95.6 ± 1.2%. In vitro drug release studies revealed a pH-dependent release of NT from Bio-Chi decorated c-MWCNTs, with a higher drug release under acidic pH conditions. Sulforhodamine B (SRB) cytotoxicity assay of different NT formulations disclosed dose-dependent cytotoxicities against SkBr3 cell line, with a superior cytotoxicity observed with NT-loaded Bio-Chi-coated c-MWCNTs, compared to either free NT or NT-loaded naked c-MWCNTs. The IC 50 values for free NT, NT-loaded c-MWCNTs and NT-loaded Bio-Chi-coated c-MWCNTs were 548.43 ± 23.1 μg mL -1 , 319.55 ± 17.9 μg mL -1 , and 257.75 ± 24.5 μg mL -1 , respectively. Interestingly, competitive cellular uptake studies revealed that surface decoration of drug-loaded c-MWCNTs with Bio-Chi permitted an enhanced uptake of c-MWCNTs by breast cancer cells, presumably, via biotin receptors-mediated endocytosis. To sum up, Bio-Chi-decorated c-MWCNTs might be a promising delivery vehicle for mediating cell-specific drug delivery to breast cancer cells., Competing Interests: The authors declare no conflict of interest., (This journal is © The Royal Society of Chemistry.)

Diabetes Mellitus is characterized by a hyperglycemic condition which can either be caused by the destruction of the beta cells or by the resistance developed against insulin in the cells. Insulin is a peptide hormone that regulates the metabolism of carbohydrates, proteins, and fats. Type 1 Diabetes Mellitus needs the use of Insulin for efficient management. However invasive methods of administration may lead to reduced adherence by the patients. Hence there is a need for a non-invasive method of administration. Oral Insulin has several merits over the conventional method including patient compliance, and reduced cost, and it also mimics endogenous insulin and hence reaches the liver by the portal vein at a higher concentration and thereby showing improved efficiency. However oral Insulin must pass through several barriers in the gastrointestinal tract. Some strategies that could be utilized to bypass these barriers include the use of permeation enhancers, absorption enhancers, use of suitable polymers, use of suitable carriers, and other agents. Several formulation types have been explored for the oral delivery of Insulin like hydrogels, capsules, tablets, and patches which have been described briefly by the article. A lot of attempts have been made for developing oral insulin delivery however none of them have been commercialized due to numerous shortcomings. Currently, there are several formulations from the companies that are still in the clinical phase, the success or failure of some is yet to be seen in the future., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Gangadharappa H.V. reports financial support was provided by JSS College of Pharmacy Mysore., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Among the various types of cancer, lung cancer accounts for the highest number of fatalities across the globe. A combination of different cancer chemotherapeutics is regarded as an effective strategy for clinical management of different cancers. Ganetespib (GAN) is a well-established hsp90 inhibitor with enhanced pharmacological properties in comparison with its first-generation counterparts. Previous preclinical studies have shown that GAN exerts significant effects against cancer cells; however, its therapeutic effects against non-small cell lung cancer (NSCLC) A549 cells, achieved by modulating the expression of the NF-κB/p65 signaling pathway, remains unexplored. In this study, the combinatorial effect of GAN and methotrexate (MTX) against lung carcinomas was investigated through both in silico and in vitro studies. A combinatorial treatment regimen of GAN/MTX exerted more significant cytotoxic effects ( p < 0.001) against A549 cells than individual treatments. The GAN/MTX combination also instigated nuclear fragmentation followed by augmentation in intracellular ROS levels ( p < 0.001). The elevated ROS in A549 cells upon exposure to GAN/MTX combinatorial regimen was concomitantly accompanied with a remarkable reduction in mitochondrial viability. In addition, it was observed that the GAN/MTX combination succeeded in elevating caspase-3 activity and downregulating the expression levels of anti-apoptotic mediators Bcl2 and survivin in NSCLC A549 cells. Most importantly, the GAN/MTX combinatorial regimen impeded the activation of the NF-kB/p65 signaling pathway via repression of the expression of E-cadherin and N-cadherin, which was confirmed by molecular docking studies. Collectively, these findings demonstrated the synergistic effect of the GAN/MTX combinatorial regimen in suppressing the growth of A549 cells by modulating the NF-κB/p65 signaling pathway.

Evident role of inflammation in cancer development and progression prompted the application of anti-inflammatory medications as a therapeutic strategy. The major bottleneck for the anti-inflammatory drugs is targeted delivery to the cancerous cell. Nanotechnology has provided safe and effective way for targeted cancer therapy. However, the complex and heterogeneous traits of cancer, incomplete information on fate and behavior of nanomedicines in human body, and lack of large-scale commercial production have slowed down the pace of nanomedicines development. To shift the paradigm from conventional cancer therapeutics to anti-inflammatory nano-therapeutics, thorough understanding of the strategies, progress, success, challenges and future perspectives are needed. The present review highlights all these aspects in addition to innovations patented on them. In fact, patent plays a vital role in protection of innovations, and further translation of lab-scale outcomes into bedside medications. Thus, the review introspects and recognizes the glitches in successful clinical translation of anti-inflammatory nanomedicines., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

One of the most significant threats in Parkinson's disease (PD) is neurodegeneration. Neurodegeneration at both nigral as well as non-nigral regions of the brain is considered responsible for disease progression in PD. The key factors that initiate neurodegeneration are oxidative stress, neuroinflammation, mitochondrial complex-1 inhibition, and abnormal α-synuclein (SNCA) protein aggregations. Nigral neurodegeneration results in motor symptoms (tremor, bradykinesia, rigidity, shuffling gait, and postural instability) whereas; non-nigral neurodegeneration is responsible for non-motor symptoms (depression, cognitive dysfunctions, sleep disorders, hallucination, and psychosis). The available therapies for PD aim at increasing dopamine levels. The medications such as Monoamine oxidase B (MAO-B) inhibitors, catechol o-methyltransferase (COMT) inhibitors, Dopamine precursor (Levodopa), dopamine agonists, and dopamine reuptake inhibitors drastically improve the motor symptoms and quality of life only in the early stages of the disease. However, dopa resistant motor symptoms (abnormality in posture, speech impediment, gait, and balance problems), dopa resistant non-motor signs (sleep problems, autonomic dysfunction, mood, and cognitive impairment, pain), and drug-related side effects (motor fluctuations, psychosis, and dyskinesias) are considered responsible for the failure of these therapies. Further, none of the treatments, alone or in combination, are capable of halting the disease progression in the long run. Therefore, there is a need to develop safe and efficient neuroprotective agents, which can slow or stop the disease progression for the better management of PD. In this review, an effort has been made to discuss the various mechanisms responsible for progressive neurodegeneration (disease progression) in PD and also multiple strategies available for halting disease progression., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Bioinspired and biomimetic micro- and nanostructures have a high significance in the field of biomedicine. In this review, the possible applications of these micro- and nanostructures that come across in our daily life and inspired by nature itself are presented. Also, the biomimetic and bioinspired systems related to micro- and nanostructures in biomedicine are also described. The role of bioinspired and biomimetic micro- and nanostructures in therapeutics, especially in anti-inflammatory and wound healing, development of bioinspired medical devices, tissue engineering, drug delivery, gene delivery, pressure sensors, and bioprinting are discussed. The biomimetic and bioinspired systems using carbon-based nanostructures, polymer nanocomposites, hybrid scaffolds, polymer networks,and protein nanostructures are also reviewed. The advantage of these bioinspired and biomimetic structures is derived from their high biocompatibility when compared to the synthetically derived micro-/nanostructures. By developing deeper knowledge and overcoming the associated challenges, these micro- and nanostructures present a promising solution for many unresolved problems in biomedicine., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Silk fibroin (SF) is a natural polymeric biomaterial that is widely adopted for the preparation of drug delivery systems. Herein, we aimed to fabricate and characterize SF nanoparticles loaded with the selective estrogen receptor modulator; tamoxifen citrate (TC-SF-NPs) and to assess their in vitro efficacy against breast cancer cell lines (MCF-7 and MDA-MB-231). TC-loaded SF-NPs were characterized for particle size, morphology, entrapment efficiency, and release profile. In addition, we examined the in vitro cytotoxicity of TC-SF-NPs against human breast cancer cell lines and evaluated the anticancer potential of TC-SF-NPs through apoptosis assay and cell cycle analysis. Drug-loaded SF-NPs showed an average particle size of 186.1 ± 5.9 nm and entrapment efficiency of 79.08%. Scanning electron microscopy (SEM) showed the nanoparticles had a spherical morphology with smooth surface. Tamoxifen release from SF-NPs exhibited a biphasic release profile with an initial burst release within the first 6 h and sustained release for 48 h. TC-SF-NPs exerted a dose-dependent cytotoxic effect against breast cancer cell lines. In addition, flow cytometry analysis revealed that cells accumulate in G 0 /G 1 phase, with a concomitant reduction of S- and G 2 -M-phase cells upon treatment with TC-SF-NPs. Consequently, the potent anticancer activities of TC-SF-NPs against breast cancer cells were mainly attributed to the induction of apoptosis and cell cycle arrest. Our results indicate that SF nanoparticles may represent an attractive nontoxic nanocarrier for the delivery of anticancer drugs.

Current discoveries as well as research findings on various types of carbon nanostructures have inspired research into their utilization in a number of fields. These carbon nanostructures offer uses in pharmacy, medicine and different therapies. One such unique carbon nanostructure includes carbon nanotubes (CNTs), which are one-dimensional allotropes of carbon nanostructure that can have a length-to-diameter ratio greater than 1,000,000. After their discovery, CNTs have drawn extensive research attention due to their excellent material properties. Their physical, chemical and electronic properties are excellent and their composites provide great possibilities for enormous nanometer applications. The current study provides a systematic review based on prior literature review and data gathered from various sources. The various research studies from many research labs and organizations were systematically retrieved, collected, compiled and written. The entire collection and compilation of this review concluded the use of CNT approaches and their efficacy and safety for the treatment of various diseases such as brain tumors or cancer via nanotechnology-based drug delivery, phototherapy, gene therapy, antiviral therapy, antifungal therapy, antibacterial therapy and other biomedical applications. The current review covers diverse applications of CNTs in designing a range of targeted drug delivery systems and application for various therapies. It concludes with a discussion on how CNTs based medicines can expand in the future.

Losartan potassium (LP) is an angiotensin receptor blocker used to treat hypertension. At higher pH, it shows poor aqueous solubility, which leads to poor bioavailability and lowers its therapeutic effectiveness. The main aim of this research was to develop a direct compressed effervescent floating matrix tablet (EFMT) of LP using hydroxyl propyl methylcellulose 90SH 15,000 (HPMC-90SH 15,000), karaya gum (KG), and an effervescent agent, such as sodium bicarbonate (SB). Therefore, an EFMT has been developed to prolong the stomach residence time (GRT) of a drug to several hours and improve its bioavailability in the stomach region. The blended powder was evaluated for pre-compression characteristics, followed by post-compression characteristics, in vitro floating, water uptake studies, and in vitro studies. The optimized formulation of EFMT was investigated for in vivo buoyancy by X-ray imaging and pharmacokinetic studies in Albino rabbits. The results revealed that the parameters of pre- and post-compression were within the USP limits. All tablets showed good floating capabilities (short floating lag time <1 min and floated for >24 h), good swelling characteristics, and controlled release for over 24 h. The Fourier-transform infrared (FTIR) and differential scanning calorimetry (DSC) spectra showed drug-polymer compatibility. The optimized formulation F3 (HPMC-90SH 15,000-KG) exhibited non-Fickian diffusion and showed 100% drug release at the end of 24 h. In addition, with the optimized formulation F3, we observed that the EFMT floated continuously in the rabbit's stomach area; thus, the GRT could be extended to more than 12 h. The pharmacokinetic profiling in Albino rabbits revealed that the relative bioavailability of the optimized LP-EFMT was enhanced compared to an oral solution of LP. We conclude that this a potential method for improving the oral bioavailability of LP to treat hypertension effectively.

Cholelithiasis is a common and frequent condition all over the world with a high prevalence rate in western countries. Individuals with cholesterol gallstone disease experience intense gastrointestinal symptoms and have a high risk of developing comorbidities like cholecystitis, Gall bladder (GB) cancer and pancreatitis. Multiple risk factors associated with cholesterol gallstones include but not limited to genetics, dietary habits, lifestyle changes, comorbid conditions and various drugs. These factors may lead to alteration in bile, cholesterol & phospholipids homeostasis in the GB, intestine and hepatocytes culminating in cholesterol gallstones formation. Surgical (cholecystectomy) and non-surgical (oral dissolution therapy) treatments are available for the disease, albeit with certain complications and high treatment cost. Thus, there is a need for interventions, complementary or alternative therapies for the treatment and prevention of cholesterol gallstones. Currently available drug therapies used for cholesterol gallstones include statins and ezetimibe. Many patients consider traditional herbal practitioners due to their promise of non-invasive and pain free management of gall stones. This present a positive shift towards generally acceptable safety and cost effectiveness of herbal treatment warranting extensive research for alternative or complementary choice such as herbal plants as an emerging area for their potential therapeutic effects. This review discusses current strategies, latest trends available in the disease pathogenesis, drug development for novel targets, risk management, newer anti-lithogenic drugs and herbal plants that target the different aspects of the disease., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Graphene nanoribbons (GNRs) are lengthened one-dimensional monolayer strips of graphene and have a hexagonal honeycomb lattice structure. The captivating properties like electrical conductivity, emerging band gap, optical property, thermal conductivity, high mechanical strength, and ultrahigh surface area make them a better candidate for biomedical applications. The properties can be significantly reformed and controlled by altering the edge functionalities and geometry. The exhibition of a wide potential window coupled with an ultra-high surface area to host sensing element makes GNR an excellent biosensing platform. Consequently, biosensing is one of the most explored applications of GNR. This review presents an overview of the characteristics, methods of synthesis, and biosensing applications of GNR. Overall, GNR is considered a promising platform for efficient signal transduction compared to conventional biosensing platforms. Further, it offers high electrical conductivity, large surface area, high adsorption, synergistic effects with combined materials, fast response, sensitivity, and selectivity., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Despite decades of research, breast cancer therapy remains a great challenge. Docetaxel is an antimicrotubule agent that is effectively used for the treatment of breast cancer. However, its clinical use is significantly hampered by its low water solubility and systemic toxicity. The current study was designed to prepare docetaxel (DXL)-loaded silk-fibroin-based nanoparticles (SF-NPs) and to screen their potential antitumor activity against breast cancer cell lines. DXL-loaded SF-NPs were prepared using a nanoprecipitation technique and were evaluated for particle size, zeta potential, entrapment efficiency, and in vitro release profile. In addition, DXL-loaded SF-NPs were screened for in vitro cytotoxicity, cellular uptake, and apoptotic potential against MCF-7 and MDA-MB-231 breast cancer cell lines. The prepared DXL-loaded SF-NPs were 178 to 198 nm in diameter with a net negative surface charge and entrapment efficiency ranging from 56% to 72%. In vitro release studies exhibited a biphasic release profile of DXL from SF-NPs with sustained drug release for 72 h. In vitro cell studies revealed that entrapment of DXL within SF-NPs significantly improved cytotoxic potential against breast cancer cell lines, compared to the free drug, and enhanced cellular uptake of DXL by breast cancer cells. Furthermore, the accumulation in the G2/M phase was significantly higher in cells treated with DXL-loaded SF-NPs than in cells treated with free DXL. Collectively, the superior antitumor activities of DXL-loaded SF-NPs against breast cancer cells, compared to free DXL, could be ascribed to improved apoptosis and cell cycle arrest. Our results highlighted the feasibility of using silk fibroin nanoparticles as a nontoxic biocompatible delivery vehicle for enhanced therapeutic outcomes in breast cancer.

In the present study, we aimed to develop a novel pH-sensitive polymeric delivery system (GG- g -PMMA) for antidiabetic therapy via grafting ghatti gum (GG) with methyl methacrylate (MMA) chains. The free radical polymerization technique was adopted to graft ghatti gum with methyl methacrylate, using ceric ammonium nitrate (CAN) as a redox initiator. The impact on grafting parameters such as grafting percentage ( G %) and grafting efficiency (GE), of monomer and initiator concentrations was evaluated. The batch with higher grafting efficiency and percentage grafting was selected and characterized by elemental analysis (C, H and N), DSC, FT-IR spectroscopy, XRD, 1 H-NMR and SEM morphology study. In addition, the efficacy of GG- g -PMMA-based pellets loaded with the hypoglycemic agent, metformin hydrochloride, to sustain drug release was investigated. In vitro release studies demonstrated a pH-dependent sustained release of the drug from GG- g -PMMA pellets. In addition, acute oral toxicity studies and histopathological analysis suggested the safety and biocompatibility of the grafted gum. Most importantly, in vivo efficacy studies underscored the efficient hypoglycemic potential of the prepared formulation, which was comparable to that of a sustained release marketed formulation. These results suggest that the developed pH-sensitive polymeric delivery system (GG- g -PMMA) might represent a promising delivery vehicle for facilitated antidiabetic therapy., Competing Interests: The authors declare no conflict of interest., (This journal is © The Royal Society of Chemistry.)

Layered double hydroxides (LDHs), also known as anionic clays or hydrotalcite-like compounds, are a class of nanomaterials that attained great attention as a carrier for drug delivery applications. The lamellar structure of this compound exhibits a high surface-to-volume ratio which enables the intercalation of therapeutic agents and releases them at the target site, thereby reducing the adverse effect. Moreover, the intercalated drug can be released in a sustained manner, and hence the frequency of drug administration can be decreased. The co-precipitation, ion exchange, manual grinding, and sol-gel methods are the most employed for their synthesis. The unique properties like the ease of synthesis, low cost, high biocompatibility, and low toxicity render them suitable for biomedical applications. This review presents the advances in the structure, properties, method of preparation, types, functionalization, and drug delivery applications of LDH. Also, this review provides various new conceptual insights that can form the basis for new research questions related to the drug delivery applications of LDH., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The silk fibroin (SF) prepared by Bombyx mori silkworms is one of the mainly abundant natural fiber and can be obtained simply and economically. SF as bio-material has superior bio-compatibility and bio-degradability. The current review provides an inclusive outline of up to date and novel developments on SF as bio-material based applications in tissue engineering and various drug delivery. SF as bio-materials was comprehensively reviewed, demonstrating the characteristics and applications of SF bio-materials in tissue engineering and drug delivery systems. Convenient regeneration, superb bio-compatibility, significant mechanical properties and versatile bio-degradability of SF has been investigated for the preparation of a range of articles such as films, spongy matrices, hydrogels, etc., and has been examined for use in a choice of tissue engineering utilization. Also, SF nanoparticles have been effectively designed and are competent to manage the release rate of biomolecules in a continuous approach with high stability. Therefore, the present review comprehensively covered the advancement made on SF based drug delivery, in vitro engineering and rejuvenation determines possibilities for additional progress in these areas., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Hand hygiene by washing with soap and water is recommended for the prevention of COVID-19 spread. Soaps and detergents are explained to act by damaging viral spike glycoproteins (peplomers) or by washing out the virus through entrapment in the micelles. Technically, soaps come under a functional category of molecules known as surfactants. Surfactants are widely used in pharmaceutical formulations as excipients. We wonder why surfactants are still not tried for prophylaxis or therapy against COVID-19? That too when many of them have proven antiviral properties. Moreover, lung surfactants have already shown benefits in respiratory viral infections. Therefore, we postulate that surfactant-based prophylaxis and therapy would be promising. We believe that our hypothesis would stimulate debate or new research exploring the possibility of surfactant-based prophylaxis and therapy against COVID-19. The success of a surfactant-based technique would save the world from any such pandemic in the future too., 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 © 2020 Elsevier Ltd. All rights reserved.)

Neurodegenerative disorders and brain tumors are major pathological conditions affecting the brain. The delivery of therapeutic agents into the brain is not as easy as to other organs or systems. The presence of the blood-brain barrier (BBB) makes the drug delivery into the brain more complicated and challenging. Many techniques have been developed to overcome the difficulties with BBB and to achieve brain-targeted drug delivery. Incorporation of the drugs into nanocarriers capable to penetrate BBB is a simple technique. Different nanocarriers have been developed including polymeric nanoparticles, carbon nanoparticles, lipid-based nanoparticles, etc. Carbon nanostructures could make a superior position among them, because of their good biocompatibility and easy penetration of BBB. Carbon-family nanomaterials consist of different carbon-based structures including zero-dimensional fullerene, one-dimensional carbon nanotube, two-dimensional graphene, and some other related structures like carbon dots and nanodiamonds. They can be used as efficient carriers for drug delivery into the brain. Apart from the drug delivery applications, they can also be used as a central nervous system (CNS) therapeutic agent; some of the carbon nanostructures have neuroregenerative activity. Their influence on neuronal growth and anti-amyloid action is also interesting. This review focuses on different carbon nanostructures for brain-targeted drug delivery and their CNS activities. As a carrier and CNS therapeutic agent, carbon nanostructures can revolutionize the treatment of brain disorders., 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 © 2020 Elsevier B.V. All rights reserved.)

Graphene nanoribbons (GNRs) are narrow lengthened strips of single-layer graphene. Among the graphene family of nanomaterials, GNRs are remarkable materials due to their attractive physical, chemical, electrical, mechanical, thermal, and optical properties. They have an ultra-high surface area. Graphene-oxide nanoribbons (GONRs), the oxygenated derivative of GNRs, offer more possibilities in the biomedicine due to their amphiphilic nature. Noncovalent and covalent modifications of these are possible for advanced biomedical applications. This review describes the properties, synthesis, surface modifications, and toxicities of GNRs, along with their biomedical applications. Their applications in drug delivery, anticancer therapy, sensing, antimicrobial therapy, imaging, gene therapy, photothermal therapy, management of spinal cord injury, bone regeneration, etc. are reviewed., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The objective of the present study was to develop a pH-sensitive drug delivery system by using polymethylmethacrylate-grafted gellan gum (PMMA-g-GG). PMMA-g-GG was synthesized by free radical polymerization reaction by using redox initiator ceric ammonium nitrate (CAN), and a series of graft copolymers were prepared with varying concentrations of methylmethacrylate (MMA) and CAN. Grafting parameters such as the percentage and efficiency of grafting were calculated, and the effect of monomer as well as initiator concentration was studied on the grafting yield. Optimization was done by one optimal response surface methodology. The batch with a better percentage grafting and grafting efficiency was selected and characterized by elemental analysis (CHN), FT-IR, DSC, PXRD, 1 H-NMR, and SEM. Furthermore, acute oral toxicity study and histopathological analysis suggested non-toxic and biocompatible nature of the grafted gum. Metformin hydrochloride pellets were prepared using PMMA-g-GG, characterized in detail, and assessed for biocompatibility and efficacy. PMMA-g-GG-based formulation (M4) exhibited a pH-sensitive as well as sustained release of the drug over the period of 12 h and the release profile followed Peppas model. In vivo efficacy studies indicated a promising antidiabetic potential of the prepared formulation. Thus, PMMA-g-GG-based formulations can be implicated as novel drug delivery systems for facilitated antidiabetic therapy in the near future. Graphical abstract.

The main purpose of the study was to develop valsartan floating tablets (VFT) via non-effervescent technique using low density polypropylene foam powder, carbopol, and xanthan gum by direct compression. Before compression, the particulate powdered mixture was evaluated for pre-compression parameters. The prepared valsartan tablets were evaluated for post-compression parameters, swelling index, floating lag time, in vitro buoyancy studies, and in vitro and in vivo X-ray imaging studies in albino rabbits. The result of all formulations for pre- and post-compression parameters were within the limits of USP. FTIR and DSC studies revealed no interaction between the drug and polymers used. The prepared floating tablets had good swelling and floating capabilities for more than 12 h with zero floating lag time. The release of valsartan from optimized formulation NF-2 showed sustained release up to 12 h; which was found to be non-Fickian release. Moreover, the X-ray imaging of optimized formulation (NF-2) revealed that tablet was constantly floating in the stomach region of the rabbit, thereby indicating improved gastric retention time for more than 12 h. Consequently, all the findings and outcomes have showed that developed valsartan matrix tablets could be effectively used for floating drug delivery system.

Respiratory infection is a viral spreading disease and a common issue, particularly in kids. The treatments are available but have so many limitations because the drawback of this disease is more morbidity and mortality in the severely immune compromised. Even, the phyto-constituent antibacterial drug Gingerol was selected to treat respiratory infection but it exhibits low bioavailability profile, less aqueous-solubility issue and most important is rapidly eliminated from the body. To overcome these problems, novel drug delivery (nanoparticle) based phytosome complexed with chitosan approach was implemented. In this research work, the phytosome (GP) was prepared by blending of gingerol with soya lecithin in organic solvent using anti-solvent precipitation technique and it was further loaded in the aqueous solution of chitosan to formulate the phytosome complexed with chitosan (GLPC). To optimize the formulations of gingerol, it was characterized for percentage yield, percentage entrapment efficiency, drug loading and particle size, physical compatibility studies etc. which demonstrated the confirmation of complex of GLPC with soya lecithin and chitosan. The % entrapment efficiency and % drug loading of GLPC was found (86.02 ± 0.18%, 08.26 ± 0.72%) and of GP (84.36 ± 0.42%, 08.05 ± 0.03%), respectively. The average particle size and zeta potential of GLPC and GP were 254.01 ± 0.05 nm (-13.11 mV), and 431.21 ± 0.90 nm (-17.53 mV), respectively which confirm the inhibition of particle aggregation by using chitosan in complex. The in vitro release rate of GP (86.03 ± 0.06%) was slower than GLPC (88.93 ± 0.33%) in pH 7.4 phosphate buffer up to 24 h by diffusion process (Korsmeyer Peppas model). The optimized GLPC and GP were shown irregular particle shapes & spherical and oval structures with smooth surface by SEM analysis. Furthermore, GLPC has shown the potent in vitro antioxidant activity, susceptible antibacterial activity and effective anti-inflammatory activity as compared to GP against stress, microbial infection and inflammation which were causable reason for the respiratory infections. GLPC has improved the significant bioavailability and also correlated the hematological values on rabbit blood against the incubation of microorganisms. Thus, the prepared nanoparticle based approach to deliver the gingerol, has the combined effect of chitosan and phytosome which shown better sustained-release profile and also prolonging the oral absorption rate of gingerol with effective antibacterial activity to treat respiratory infection., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Pancreatic cancer (PC) is one of the most fatal solid tumors, resulting in more than 250,000 deaths per year globally. It is the eighth leading cause of death from cancer in men and women throughout the world and is now third leading cause of cancer-related deaths in the United States. In addition, the worldwide occurrence of PC ranges from 1 to 10 cases per 100,000 people, indicating a higher incidence in developed countries. Most patients with locally advanced or metastatic disease are not candidates for curative resection due to enormously poor prognosis. Substantial efforts have been taken during the past decade to distinguish better treatments in the absence of efficient screening methods. Regardless of wide-ranging efforts, various systems and therapies have shown insufficient efficacy for PC patients. Therefore, the development of novel drug delivery systems, strategies, and diverse therapeutic approaches to improve the range of active molecules for the treatment of PC is critical. Currently, cancer research focuses on improving the treatment of PC via diverse novel drug delivery systems of chemotherapeutic agents. These novel drug delivery systems consist of nanoparticles and liposomes. Strategies or therapeutic approaches intended for PC include radiation therapy, ablation therapy, and gene therapy. These systems and approaches can carry the drug molecules to targeted cancer cells to enhance the effectiveness of tumor penetration. The present review encloses existing novel drug carrier systems and approaches for PC management.

Background: Prostate cancer (PC) is a prostate gland cells carcinoma, the foremost reason of cancer deaths in men in developed countries, representing most common malignancy in adult males. The key obstacle to achieve practicable therapeutic effect of active drugs and capable hopeful agents including proteins and peptides, and nucleic acid for prostate cancer is the scarcity of targeted drug delivery to cells of prostate cancer. As a result, need for novel systems, strategies or therapeutic approaches to enhance the assortment of active agents meant for prostate cancer becomes an important criterion. Currently cancer research focuses on improving treatment of prostate cancer using various novel drug delivery systems of chemotherapeutic agents. These novel drug delivery systems comprise nanoparticles and liposomes. Also, strategies or therapeutic approaches intended for the prostate cancer include radiation therapy for localized prostate cancer, hormonal therapy for suppressing tumor growth, and gene-and-immunologic therapy. These systems and approaches can deliver the drugs to their selected or targeted cancer cells for the drug release in cancer atmosphere of prostate thereby enhancing the effectiveness of tumor penetration., Objective: The objective was to collect and report the recent research findings to manage the PC. Present review encloses existing diverse novel drug delivery systems and approaches intended for the management of PC., Conclusion: The reported miscellaneous novel drug delivery systems along with the diverse therapies are seem to be precise, secure and relatively effective; and in consequence could lead to a new track for obliteration of prostate cancer., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

The aim of the work is to modify the solubility and bioavailability of Losartan potassium, by employing noneffervescent floating drug delivery (tablet dosage forms). Non-effervescent systems are a type of floating drug delivery systems, that have been used to boost the gastric residence and the floatation time in the gastro intestinal tract. The study included formulation of floating tablets using polymers like Chitosan and Karaya gum as matrix forming agents. Accurel(®) MP 1000 was used as floating agent. The tablets were prepared by direct compression technique. FTIR, DSC studies conformed that there was no incompatibility between the polymer and the drug. Tablet preformulation parameters were within the Pharmacopoeial limit. Tablet showed zero lag time, contisnuance of buoyancy for >12 h. The tablet showed good in vitro release. Drug release was through swelling and abided by the gellation mechanism. In vivo X-ray studies depicted that tablets continued to float in the GIT for 12 h. Accelerated stability showed that, tablets were stable for over 6 month. Thus the prepared non-effervescent floating tablet of Losartan potassium can be used for the treatment of hypertension for more than 12 h with single dose administration.

Microsponge is a microscopic sphere capable of absorbing skin secretions, therefore reducing the oiliness of the skin. Microsponge having particle size of 10-25 microns in diameter, have wide range of entrapment of various ingredients in a single microsponges system and release them at desired rates. Conventional topical preparations have various disadvantages due to irritancy, odour, greasiness and patient compliance. In many topical dosage forms fail to reach the systemic circulation in sufficient amounts in few cases. These problems overcome by the usage of formulation as microsponge in the areas of research. Drug release in microsponge is done by the external stimuli like pH, temperature and rubbing. It has several advantageous over the other topical preparations in being non-allergenic, non-toxic, non-irritant and non- mutagenic. These microsponges are used in the sun screens, creams, ointments, over-the-counter skin care preparations, recently nanosponge were reported in literature used in delivery of drug by the use of cyclodextrins to enhance the solubility of poorly water soluble drugs, which are meant for topical application.

To minimize the unwanted toxic effects of anti-anginal ranolazine by kinetic control of drug release, it was entrapped into gastro-resistant, biodegradable eudragit (EU) and ethyl cellulose (EC) binary blend using phase separation method. Ten formulations were prepared using different polymer blend ratios and solvent. The prepared microparticles were characterized for micromeritic properties, polymer drug compatibility by Fourier Transform Infrared Spectroscopy (FT-IR) and Differential Scannibg Calorimetry (DSC), and surface morphology by Scanning Electron Micrography (SEM). The yield of microparticles was up to 90% and more than 98% of the isolated microparticles are having volume mean diameter of 285 μm. The obtained angle of repose, percentage Carr's index and tapped density values were within the limits indicating good flow properties. The surface morphology revealed that particles were free-flowing, spherical, with minute pores and invert dents on the surface. The prepared microparticles were evaluated for percentage yield, encapsulation efficiency and in vitro release studies. FT-IR and DSC studies showed no chemical interaction between the drug and used polymers The in vitro drug release studies were carried out using pH 1.2 acid buffer and pH 7.4 phosphate buffer. EU acts as an excellent pH-dependent binder and helps to release the drug in the intestine. The drug release kinetics followed different transport mechanisms. Increasing the weight fractions of EU and decreased EC helps to control the drug release from the particles. From the differential (f(1)) and similarity factor (f(2)), Formulation F5 was the formulation most similar to the commercially available oral formulation as reference standard. The drug release performance was greatly affected by the materials used in microparticle preparations, which allow absorption in the intestinal tract.