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Pharmaceutical Nanotechnology - Current Issue
Volume 13, Issue 1, 2025
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Emerging Lipid-based Carriers for Systematic Utilization in the Pharmaceutical and Biomedical Sciences: A Review
Emerging lipid-based carriers are revolutionizing drug delivery in the pharmaceutical and biomedical sciences. These innovative carriers harness the unique properties of lipids to improve the solubility, stability, and targeted delivery of therapeutic agents, ushering in a new era of precision medicine. Lipid-based carriers, such as liposomes, lipid nanoparticles, and solid lipid nanoparticles, offer several advantages. They can encapsulate both hydrophilic and hydrophobic drugs, enabling the delivery of a wide range of compounds. Additionally, lipids are biocompatible and biodegradable, minimizing the risk of toxicity. Their ability to mimic cell membranes allows for enhanced cellular uptake and controlled release, optimizing drug efficacy while minimizing side effects. Furthermore, lipid-based carriers are ideal for delivering drugs to specific sites within the body. By modifying the lipid composition, surface charge, and size, researchers can tailor these carriers to target tumours, inflamed tissues, or specific cells, improving therapeutic outcomes and reducing systemic toxicity. In summary, emerging lipid-based carriers are poised to transform pharmaceutical and biomedical sciences by addressing critical challenges in drug delivery. These carriers enhance drug stability, bioavailability, and targeted delivery, offering the potential to revolutionize the treatment of various diseases and improve patient outcomes. As research in this field continues to advance, we can expect even more sophisticated lipid-based carrier systems to emerge, further expanding the possibilities for precision medicine. This review focuses on the contribution of lipid carriers in the pharmaceutical and biomedical sciences.
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Solid Lipid Nanoparticles as an Innovative Lipidic Drug Delivery System
Authors: Suchita Waghmare, Rohini Palekar, Lata Potey, Pramod Khedekar, Prafulla Sabale and Vidya SabaleIn order to overcome some of the drawbacks of traditional formulations, increasing emphasis has recently been paid to lipid-based drug delivery systems. Solid lipid nanoparticles (SLNs) are promising delivery methods, and they hold promise because of their simplicity in production, capacity to scale up, biocompatibility, and biodegradability of formulation components. Other benefits could be connected to a particular route of administration or the makeup of the ingredients being placed into these delivery systems. This article aims to review the significance of solid lipid nanocarriers, their benefits and drawbacks, as well as their types, compositions, methods of preparation, mechanisms of drug release, characterization, routes of administration, and applications in a variety of delivery systems with a focus on their efficacy.
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Light Sensitive Liposomes: A Novel Strategy for Targeted Drug Delivery
Authors: Chintan Aundhia, Ghanshyam Parmar, Chitrali Talele, Dipali Talele and Avinsh Kumar SethLight-sensitive liposomes have emerged as a promising platform for drug delivery, offering the potential for precise control over drug release and targeted therapy. These lipid-based nanoparticles possess photoresponsive properties, allowing them to undergo structural changes or release therapeutic payloads upon exposure to specific wavelengths of light. This review presents an overview of the design principles, fabrication methods, and applications of light-sensitive liposomes in drug delivery. Further, this article also discusses the incorporation of light-sensitive moieties, such as azobenzene, spiropyran, and diarylethene, into liposomal structures, enabling spatiotemporal control over drug release. The utilization of photosensitizers and imaging agents to enhance the functionality and versatility of light-sensitive liposomes is also highlighted. Finally, the recent advances, challenges, and future directions in the field, emphasizing the potential for these innovative nanocarriers to revolutionize targeted therapeutics, are also discussed.
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Enhancing Gene Therapy through Ultradeformable Vesicles for Efficient siRNA Delivery
Authors: Chintan Aundhia, Nirmal Shah, Chitrali Talele, Aarti Zanwar, Mamta Kumari and Sapana PatilGene therapy is a revolutionary approach aimed at treating various diseases by manipulating the expression of specific genes. The composition and formulation of ultra-deformable vesicles play a crucial role in determining their properties and performance as siRNA delivery vectors. In the development of ultra-deformable vesicles for siRNA delivery, careful lipid selection and optimization are crucial for achieving desirable vesicle characteristics and efficient siRNA encapsulation and delivery. The stratum corneum acts as a protective barrier, limiting the penetration of molecules, including siRNA, into the deeper layers of the skin. Ultradeformable vesicles offer a promising solution to overcome this barrier and facilitate efficient siRNA delivery to target cells in the skin. The stratum corneum, the outermost layer of the skin, acts as a significant barrier to the penetration of siRNA. These engineering approaches enable the production of uniform and well-defined vesicles with enhanced deformability and improved siRNA encapsulation efficiency. Looking ahead, advancements in ultra-deformable vesicle design and optimization, along with continued exploration of combination strategies and regulatory frameworks, will further drive the field of ultra-deformable vesicle-based siRNA delivery.
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- Materials Science and Nanotechnology, Nanotechnology, Pharmacology
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Lipids Fortified Nano Phytopharmaceuticals: A Breakthrough Approach in Delivering Bio-actives for Improved Therapeutic Efficacy
Phytopharmaceuticals, derived from natural sources, manifest tremendous potential for therapeutic applications. Nevertheless, effective delivery of these bio-actives presents significant challenges. A breakthrough in fortifying phytopharmaceuticals within phosphatidylcholine is a promising remedy to overcome solubility, permeability, and other related drawbacks. This intrinsic lipid, which is obtained from both natural and synthetic sources, confers numerous benefits, encompassing heightened solubility, augmented bioavailability, and enhanced stability. The conjugation of phytopharmaceuticals with phosphatidylcholine enables improved dermal permeation, absorption, targeted distribution, and the possibility of synergistic results, eventually improving therapeutic efficacy. Additionally, the use of phytopharmaceuticals enriched with phosphatidylcholine presents a promising route for overcoming the limitations imposed by conventional delivery techniques, encouraging more effective treatments. The review provides a thorough analysis of phosphatidylcholine-incorporated phytopharmaceuticals as nanomedicine with variables that significantly affect their therapeutic efficacy. Moreover, the review elaborates on how phosphatidylcholine improves solubility, permeability, and tissue distribution and boosts the potential of phytopharmaceuticals. Further, the review underscores the significance of nano-formulation strategies, analytical methodologies, and forthcoming prospects to propel this field forward. Furthermore, the review emphasizes the potential inherent in this innovative approach while highlighting the importance of additional research endeavors and collaborative initiatives to unlock the therapeutic benefits of phosphatidylcholine-fortified phytopharmaceuticals, enhancing patient well-being.
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Core-Shell Nanoparticles for Pulmonary Drug Delivery
More LessNanoscale drug delivery systems have provoked interest for application in various therapies on account of their ability to elevate the intracellular concentration of drugs inside target cells, which leads to an increase in efficacy, a decrease in dose, and dose-associated adverse effects. There are several types of nanoparticles available; however, core-shell nanoparticles outperform bare nanoparticles in terms of their reduced cytotoxicity, high dispersibility and biocompatibility, and improved conjugation with drugs and biomolecules because of better surface characteristics. These nanoparticulate drug delivery systems are used for targeting a number of organs, such as the colon, brain, lung, etc. Pulmonary administration of medicines is a more appealing method as it is a non-invasive route for systemic and locally acting drugs as the pulmonary region has a wide surface area, delicate blood-alveolar barrier, and significant vascularization. A core-shell nano-particulate drug delivery system is more effective in the treatment of various pulmonary disorders. Thus, this review has discussed the potential of several types of core-shell nanoparticles in treating various diseases and synthesis methods of core-shell nanoparticles. The methods for synthesis of core-shell nanoparticles include solid phase reaction, liquid phase reaction, gas phase reaction, mechanical mixing, microwave-assisted synthesis, sono-synthesis, and non-thermal plasma technology. The basic types of core-shell nanoparticles are metallic, magnetic, polymeric, silica, upconversion, and carbon nanomaterial-based core-shell nanoparticles. With this special platform, it is possible to integrate the benefits of both core and shell materials, such as strong serum stability, effective drug loading, adjustable particle size, and immunocompatibility.
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- Materials Science and Nanotechnology, Nanotechnology, Pharmacology
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Overcoming Solubility Challenges: Self-emulsifying Systems for Enhancing the Delivery of Poorly Water-Soluble Antiviral Drugs
The primary goal of drug formulation is to improve a drug’s bioavailability in the body. However, poorly water-soluble drugs present challenging issues related to their solubility and bioavailability factors. Emerging technologies, such as lipid-based drug delivery systems, including micro- or nanoemulsifying drug delivery systems, have become increasingly relevant to address the above challenges. This review presents a thorough overview of self-emulsifying drug delivery systems (SEDDS). It covers the properties, principles, self-emulsification mechanism, formulation strategies, and characterization methods of SEDDS. This review also addresses the delivery of antiviral agents through SEDDS. Moreover, it summarizes the marketed formulations of SEDDS consisting of antiviral agents. This review offers a comprehensive and valuable resource for future perspectives on SEDDS and their potential applications in antiviral drug delivery.
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Unveiling Spanlastics as a Novel Carrier for Drug Delivery: A Review
Authors: Dipanjan Karati, Swarupananda Mukherjee and Bhupendra G. PrajapatiInnovative colloidal preparations that can alter the pharmacological properties of drugs have been made possible by the advancement of nanotechnology. Recent advances in the sciences of the nanoscale have led to the creation of new methods for treating illnesses. Developments in nanotechnology may lessen the side effects of medicine by using effective and regulated drug delivery methods. A promising drug delivery vehicle is spanlastics, an elastic nanovesicle that can transport a variety of drug compounds. Spanlastics have expanded the growing interest in many types of administrative pathways. Using this special type of vesicular carriers, medications intended for topical, nasal, ocular, and trans-ungual treatments are delivered to specific areas. Their elastic and malleable structure allows them to fit into skin pores, making them ideal for transdermal distribution. Spanlastic is composed of non-ionic surfactants or combinations of surfactants. Numerous studies have demonstrated how spanlastics significantly improve, drug bioavailability, therapeutic effectiveness, and reduce medication toxicity. The several vesicular systems, composition and structure of spanlastics, benefits of spanlastics over alternative drug delivery methods, and the process of drug penetration via skin are all summarized in this paper. Additionally, it provides an overview of the many medications that may be treated using spanlastic vesicles. The primary benefits of these formulations were associated with their surface properties, as a variety of proteins might be linked to the look. For instance, procedure assessment and gold nanoparticles were employed as biomarkers for different biomolecules, which included tumor label detection. Anticipate further advancements in the customization and combining of spanlastic vesicles with appropriate zeta potential to transport therapeutic compounds to specific areas for enhanced disease treatment.
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- Materials Science and Nanotechnology, Nanotechnology, Pharmacology
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A Review on Lipid-based Nanoformulations for Targeting Brain through Non-invasive Nasal Route
Authors: Nirvesh Chaudhri, Vaibhav Rastogi and Anurag VermaThe nasal method for administering nanoformulations to the brain has been examined and proven successful by prior investigators. For the treatment of central nervous system (CNS) disorders such as neuropsychiatric, depression, Alzheimer and anxiety, intranasal administration has become more popular for delivering drugs to the brain. This method offers direct transport through neuronal pathways. The lipid-based nanocarriers like nanostructured lipid carriers (NLC) appear more favorable than other nanosystems for brain administration. The nanostructured lipid carriers (NLC) system can quickly transform into a gelling system to facilitate easy administration into the nasal passages. The various compatibility studies showed that the other lipid structured-based formulations may not work well for various reasons, including a low drug filing capacity; during storage, the formulation showed changes in the solid lipid structures, which gives a chance of medication ejection. Formulations containing NLC can minimize these problems by improving drug solubility and permeation rate by incorporating a ratio of liquid lipids with solid lipids, resulting in improved stability during storage and drug bioavailability because of the higher drug loading capacity. This review aimed to find and emphasize research on lipid-based nanocarrier formulations that have advanced the treatment of central nervous system illnesses using nasal passages to reach the targeted area's drug molecules.
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Uncovering the Emerging Prospects of Lipid-based Nanoparticulate Vehicles in Lung Cancer Management: A Recent Perspective
Authors: Dhruv Sanjay Gupta and Divya SuaresLung cancer, a leading cause of cancer-related deaths globally, is gaining research interest more than ever before. Owing to the burden of pathogenesis on the quality of life of patients and subsequently the healthcare system, research efforts focus on its management and amelioration. In an effort to improve bioavailability, enhance stability, minimize adverse effects and reduce the incidence of resistance, nanotechnological platforms have been harnessed for drug delivery and improving treatment outcomes. Lipid nanoparticles, in particular, offer an interesting clinical opportunity with respect to the delivery of a variety of agents. These include synthetic chemotherapeutic agents, immunotherapeutic molecules, as well as phytoconstituents with promising anticancer benefits. In addition to this, these systems are being studied for their usage in conjunction with other treatment strategies. However, their applications remain limited owing to a number of challenges, chiefly clinical translation. There is a need to address the scalability of such technologies, in order to improve accessibility. The authors aim to offer a comprehensive understanding of the evolution of lipid nanoparticles and their application in lung cancer, the interplay of disease pathways and their mechanism of action and the potential for delivery of a variety of agents. Additionally, a discussion with respect to results from preclinical studies has also been provided. The authors have also provided a well-rounded insight into the limitations and future perspectives. While the possibilities are endless, there is a need to undertake focused research to expedite clinical translation and offer avenues for wider applications in disease management.
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Nanostructured Lipid Carrier-loaded In Situ Gel for Ophthalmic Drug Delivery: Preparation and In Vitro Characterization Studies
Authors: Vidya Sabale, Vaishnavi Belokar, Manasi Jiwankar and Prafulla SabaleBackgroundNanostructured lipid carriers (NLCs) are explored as vehicles for ophthalmic drug delivery owing to their better drug loading, good permeation, and satisfactory safety profile.
ObjectivesThe purpose of the study was to fabricate and characterize an in situ ocular gel of loratadine as a model drug based on NLCs to enhance the drug residence time.
MethodsNLCs were fabricated using the microemulsion method in which solid lipid as Compritol 888 ATO, lipid as oleic acid, surfactant as Tween 80, and isopropyl alcohol as co-surfactant as alcohol were used. Based on the evaluation of formulation batches of NLCs, the optimized batch was selected and further utilized for the formulation of in situ gel containing Carbopol 934 and HPMC K15M as gelling agents, and characterized.
ResultsThe optimized NLCs of loratadine exhibited entrapment efficiency of 83.13 ± 0.13% and an average particle size of 18.98 ± 1.22 nm. Drug content and drug release were found to be 98.67 and 92.48%, respectively. Excellent rheology and mucoadhesion were demonstrated by the loratadine NLC-loaded in situ gel to enhance its attachment to the mucosa. NLC-based in situ ocular gel showed the desired results for topical administration. The prepared gel was observed to be non-irritating to the eye.
ConclusionThe optimized NLC-based in situ gel formulation presented better corneal retention and it was found to be stable, offering sustained release of the drug. Thus, the joined system of sol-gel was found promising for ophthalmic drug delivery.
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Optimizing Neuroprotective Nano-structured Lipid Carriers for Transdermal Delivery through Artificial Neural Network
Authors: Saloni Dalwadi, Vaishali Thakkar and Bhupendra PrajapatiBackgroundDementia associated with Alzheimer’s disease (AD) is a neurological disorder. AD is a progressive neurodegenerative condition that predominantly impacts the elderly population, although it can also manifest in younger people through the impairment of cognitive functions, such as memory, cognition, and behaviour. Donepezil HCl and Memantine HCl are encapsulated in Nanostructured Lipid Carriers (NLCs) to prolong systemic circulation and minimize the systemic side effects.
ObjectiveThis work explores the use of data mining tools to optimize the formulation of NLCs comprising of Donepezil HCl and Memantine HCl for transdermal drug delivery. Neuroprotective drugs and excipients are utilized for protecting the nervous system against damage or degeneration.
MethodsThe NLCs were formulated using a high-speed homogenization technique followed by ultrasonication. NLCs were optimized using Box Behnken Design (BBD) in Design Expert Software and artificial neural network (ANN) in IBM SPSS statistics. The independent variables included the ratio of solid lipid to liquid lipid, the percentage of surfactant, and the revolutions per minute (RPM) of the high-speed homogenizer.
ResultsThe NLCs that were formulated had a mean particle size ranging from 67.0±0.45 to 142.4±0.52 nm. Both drugs have a %EE range over 75%, and Zeta potential was determined to be -26±0.36 mV. CryoSEM was used to do the structural study. The permeation study showed the prolonged release of the formulation.
ConclusionThe results indicate that NLCs have the potential to be a carrier for transporting medications to deeper layers of the skin and reaching systemic circulation, making them a suitable formulation for the management of Dementia. Both ANN and BBD techniques are effective tools for systematically developing and optimizing NLC formulation.
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Preparation and In-vitro Characterization of Solid Lipid Nanoparticles Containing Artemisinin and Curcumin
BackgroundMalaria remains a formidable public health obstacle across Africa, Southeast Asia, and portions of South America, exacerbated by resistance to antimalarial medications, such as artemisinin-based combinations. The combination of curcumin and artemisinin shows promise due to its potential for dose reduction, reduced toxicity, synergistic effects, and suitability for drug delivery improvement.
ObjectivesThis research aims to enhance the solubility and dissolution rates of curcumin and artemisinin by employing Solid Lipid Nanoparticles (SLNs). Oral delivery of both drugs faces challenges due to their poor water solubility, inefficient absorption, and rapid metabolism and elimination.
MethodsThe study focuses on formulating and optimizing Solid Lipid Nanoparticles (SLNs) encapsulating artemisinin (ART) and curcumin (CUR). SLNs were developed using the hot homogenization method, incorporating ultrasonication. Drug-excipient compatibility was evaluated using Differential Scanning Calorimetry (DSC). Lipid and surfactant screening was performed to select suitable components. A 32 full factorial design was utilized to investigate the influence of lipid and surfactant concentrations on key parameters, such as entrapment efficiency (%EE) and cumulative drug release (%CDR). Additionally, evaluations of %EE, drug loading, particle size, zeta potential, and in-vitro drug release were conducted.
ResultsSuccessful development of artemisinin and curcumin SLNs was achieved using a full factorial design, demonstrating controlled drug release and high entrapment efficiency. The optimized nanoparticles exhibited a size of 114.7nm, uniformity (PDI: 0.261), and a zeta potential of -9.24 mV. Artemisinin and curcumin showed %EE values of 79.1% and 74.5%, respectively, with cumulative drug release of 85.1% and 80.9%, respectively. The full factorial design indicated that increased lipid concentration improved %EE, while higher surfactant concentration enhanced drug release and %EE. Stability studies of the optimized batch revealed no alterations in physical or chemical characteristics.
ConclusionThe study successfully developed Solid Lipid Nanoparticles (SLNs) for artemisinin and curcumin, achieving controlled drug release, high entrapment efficiency, and desired particle size and uniformity. This advancement holds promise for enhancing drug delivery of herbal formulations.
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Nose-to-brain Drug Delivery System: An Emerging Approach to Chemotherapy-induced Cognitive Impairment
The rise in global cancer burden, notably breast cancer, emphasizes the need to address chemotherapy-induced cognitive impairment, also known as chemobrain. Although chemotherapy drugs are effective against cancer, they can trigger cognitive deficits. This has triggered the exploration of preventive strategies and novel therapeutic approaches. Nanomedicine is evolving as a promising tool to be used for the mitigation of chemobrain by overcoming the blood-brain barrier (BBB) with innovative drug delivery systems. Polymer and lipid-based nanoparticles enable targeted drug release, enhancing therapeutic effectiveness. Utilizing the intranasal route of administration may facilitate drug delivery to the central nervous system (CNS) by circumventing first-pass metabolism. Therefore, knowledge of nasal anatomy is critical for optimizing drug delivery via various pathways. Despite challenges, nanoformulations exhibit the potential in enhancing brain drug delivery. Continuous research into formulation techniques and chemobrain mechanisms is vital for developing effective treatments. The intranasal administration of nanoformulations holds promise for improving therapeutic outcomes in chemobrain management. This review offers insights into potential future research directions, such as exploring novel drug combinations, investigating alternative delivery routes, or integrating emerging technologies to enhance the efficacy and safety of nanoformulations for chemobrain management.
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Preparation, In-vitro, Ex-vivo, and Pharmacokinetic Study of Lasmiditan as Intranasal Nanoemulsion-based In Situ Gel
Authors: Saba Abdulhadi Jabir and Nawal A. RajabBackgroundLasmiditan (LAS) is a recently developed antimigraine drug and was approved in October, 2019 for the treatment of acute migraines; however, it suffers from low oral bioavailability, which is around 40%.
ObjectivesThis study aimed to improve the LAS bioavailability via formulation as nanoemulsion-based in situ gel (NEIG) given intranasally and then compare the traditional aqueous-LAS-suspension (AQS) with the two successful intranasal prepared formulations (NEIG 2 and NEIG 5) in order to determine its relative bioavailability (F-relative) via using rabbits.
MethodsTwo successfully prepared nanoemulsion (NE) formulas, a and b, were selected for the incorporation of different percentages of pH-sensitive in situ gelling polymer (Carbopol 934) to prepare NEIGs 1, 2, 3, 4, 5, and 6. The pH, gelation capacity, gel strength, and viscosity were predicted for the prepared NEIGs. The release (in vitro) and the nasal permeation (ex vivo) were determined for NEIG 2 and 5, and then both were subjected to pharmacokinetics in vivo studies. Eighteen male rabbits weighing 2.0 to 2.5 kg were employed in the parallel design study. The body surface area (BSA) normalization method was applied for LAS dose calculation. Serial blood samples were taken out and subjected to drug analysis using the HPLC method previously developed and validated by Kumar et al. Primary pharmacokinetics parameters, including maximum drug concentration in plasma (C-max), time to reach C-max (T-max), and area under the concentration-time curve from time zero to affinity (AUCt0-∞) were calculated. Both NE (a and b), together with NEIG (2 and 5) formulas, were subjected to the stability study. Finally, a nasal ciliotoxicity study was carried out to evaluate the nasal toxicity of developed NEIGs 2 and 5.
ResultsThe results showed that NEIGs 2 and 5 could be selected as the optimized NEIGs as both achieved 100% permeation within 20 min and then released within 25 and 35 min, respectively, thus achieving 3.3 folds with higher permeation percentages as compared to the AQS. Both NEIGs 2 and 5 exerted comparable release and permeation values as the corresponding NE a and b with more residence time in order to overcome the normal nasal physiological clearance. The values of C-max, T-max, and AUC0- ∞ for NEIG 2 and NEIG 5 were 8066 ± 242 ng/ml, 0.75 ± 0.05 h, 19616.86 ± 589 ng. h/ml, and 7975.67 ± 239 ng/ml, 1.0 ± 0.05 h, 17912.36 ± 537 ng. h/ml, respectively, compared to the traditional AQS, which is equal to 4181.09 ± 125 ng/ml, 2 ± 0.2 h, and 8852.27 ± 266 ng. h/ml, respectively.
It was discovered that NEIGs 2 and 5 had better intranasal delivery of LAS and could significantly (p < 0.05) achieve a higher value of permeability coefficient (3.3 folds) and 2.5 folds improvement in bioavailability when compared to AQS. The NE a, NE b, NEIG2, and NEIG5 formulations showed good stability at various temperatures. According to the nasal ciliotoxicity study, the nasal mucosal membrane, which was treated with NEIG 5, showed irritation with a bit of damage. However, damage was not observed when it was treated with NEIG 2, indicating the biocompatibility of the last one to be selected as the optimum formula.
ConclusionNEIG 2 and NEIG 5 are promising new intranasal formulas with a faster onset of action and greater bioavailability than the oral dosage form (AQS). Finally, the selected optimum gold formula that will be ready for further clinical study is NEIG 2.
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RES-CMCNPs Enhance Antioxidant, Proinflammatory, and Sensitivity of Tumor Solids to γ-irradiation in EAC-Bearing Mice
ObjectivesResveratrol (Res) is a bifunctional compound found in numerous plants, including grapes and mulberries. Nanotechnology has promising applications in medicine. The ability of various nanomaterials to serve as radiosensitizers against tumor cells were reported in several manuscripts. The present investigation aimed to assess the antitumor and radiosensitizing effects of Res-CMCNPs on EAC-bearing mice.
MethodsRes-CMCNPs have been developed using the CMC emulsification cross-linking technique. Entrapment efficiency (%), particle size, Polydispersity index and ZETA potential, UV, FT-IR spectra, and drug release were evaluated and described for RES-CMCNPs. The radiosensitizing properties of RES-CMCNPs were also evaluated in vitro and in vivo against EAC-carrying rodents. The LD50 of Res-CMCNPs was estimated and its 1/20 LD50 was prepared for treating EAC transplanted mice.
ResultsThe results revealed that the Res-CMCNPs exhibited a high entrapment efficiency (85.46%) and a size of approximately 184.60 ±17.36 nm with zeta potential value equals -51.866 mv. Also, the UV spectra of Res and Res-CMCNPs have strong absorption at 225 and 290 nm. The percentage of resveratrol release at pHs 5.8 and 7.4 was found to be 56.73% and 51.60%, respectively, after 24 h at 100 rpm. Also, the FTIR analysis confirmed the chemical stability of resveratrol in Res-CMCNPs cross-linking. The IC50 values of Res-CMCNPs against EAC cells viability were 32.99, 25.46, and 22.21 µg after 24-, 48- and 72 h incubation, respectively, whereas those of Res-CMCNPs in combination with γ-irradiation after 6-, 10 and 12-mins exposure were 24.07, 16.06 and 7.48 µg, respectively. Also, the LD50 of Res-CMCNPs was 2180 mg/kg.b.w. The treatment of EAC-bearing mice with Res-CMCNPs plus γ-irradiation improved plasma levels of NO, caspase-3, P53 and NF-kB levels as well as liver MDA, GSH, SOD, CAT, LT-B4, aromatase, Bax, Bcl2 and TGF-β levels and exhibited more significant anticancer activity than administration of Res-CMCNPs and/or exposure to γ-irradiation individually. On the other hand, administration of Res-CMCNPs in combination with γ-irradiation attenuated liver mRNAs (21, 29b, 181a, and 451) gene expression.
ConclusionGrafting resveratrol onto carboxymethyl chitosan appears to be a promising strategy for cancer therapy as a radiosensitizer, potentiating tumor cells' sensitivity to radiation by improving levels of proinflammatory features and antioxidant biomarkers.
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