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1.
Semin Cancer Biol ; 86(Pt 2): 678-696, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35452820

RESUMO

Cancer is one of the dreadful diseases worldwide. Surgery, radiation and chemotherapy, are the three basic standard modes of cancer treatment. However, difficulties in cancer treatment are increasing due to immune escape, spreading of cancer to other places, and resistance of cancer cells to therapies. Various signaling mechanisms, including PI3K/Akt/mTOR, RAS, WNT/ß-catenin, TGF-beta, and notch pathways, are involved in cancer resistance. The adaptive inflammatory response is the initial line of defence against infection. However, chronic inflammation can lead to tumorigenesis, malignant transformation, tumor growth, invasion, and metastasis. The most commonly dysregulated inflammatory pathways linked to cancer include NF-κB, MAPK, JAK-STAT, and PI3K/AKT. To overcome major hurdles in cancer therapy, nanomedicine is receiving much attention due to its role as a vehicle for delivering chemotherapeutic agents that specifically target tumor sites. Several biocompatible nanocarriers including polymer and inorganic nanoparticles, liposomes, micellar nanoparticles, nanotubes, and exosomes have been extensively studied. Exosome has been reported as an important potential system that could be effectively used as a bioinspired, bioengineered, and biomimetic drug delivery solution considering its toxicity, immunogenicity, and rapid clearance by the mononuclear phagocyte system. Exosome-mimetic vesicles are receiving much interest for developing nano-sized delivery systems. In this review, exosomes in detail as well as certain other nanocarriers, and their potential therapeutic roles in cancer therapy has been thoroughly discussed. Additionally, we also reviewed on oncogenic and tumor suppressor proteins, inflammation, and their associated signaling pathways and their interference by exosomes based nanomedicine.


Assuntos
Exossomos , Neoplasias , Humanos , Nanomedicina , Exossomos/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Inflamação/metabolismo
2.
Molecules ; 28(7)2023 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-37049892

RESUMO

The objective of this study was to synthesize a novel choline hydroxide ionic liquid-based tooth bleaching gel. Ionic liquid-based gels were synthesized and characterized using FTIR along with pH testing. Tooth sample preparation was carried out in line with ISO 28399:2020. The effects of synthesized gels on tooth samples were tested. Tooth samples were stained and grouped into three experimental groups: EAI (22% choline hydroxide gel), EAII (44% choline hydroxide gel), and EB (choline citrate gel) and two control groups: CA (commercial at-home 16% carbamide peroxide gel) and CB (deionized water). The tooth color analysis, which included shade matching with the Vitapan shade guide (n = 2), and digital colorimetric analysis (n = 2) were evaluated. The surface characteristics and hardness were analyzed with 3D optical profilometry, Scanning Electron Microscopy (SEM), Energy Dispersive X-ray Spectroscopy (EDX), and Microhardness testing (n = 3), respectively. The tooth color analysis (Vitapan shade guide) revealed that all the tooth samples treated with synthesized choline citrate gel (EB) showed an A1 shade as compared to the other four groups, giving a range of shades. An analysis of the ΔE values from digital colorimetry; EAI, EAII, CA, and CB showed ΔE values in a range that was clinically perceptible at a glance. However, EB showed the highest value of ΔE. The mean microhardness values for the five groups showed that the effects of three experimental gels i.e., 44% choline hydroxide, 22% choline hydroxide, and choline citrate, on the microhardness of the tooth samples were similar to that of the positive control, which comprised commercial at-home 16% carbamide peroxide gel. SEM with EDX of three tested subgroups was closely related in surface profile, elemental composition, and Ca/P ratio. The roughness average values from optical profilometry of four tested subgroups lie within approximately a similar range, showing a statistically insignificant difference (p > 0.05) between the tested subgroups. The synthesized novel experimental tooth bleaching gels displayed similar tooth bleaching actions without any deleterious effects on the surface characteristics and microhardness of the treated tooth samples when compared with the commercial at-home tooth bleaching gel.


Assuntos
Líquidos Iônicos , Clareamento Dental , Clareamento Dental/métodos , Peróxido de Carbamida , Peróxidos/química , Ureia/química , Análise Custo-Benefício , Géis , Peróxido de Hidrogênio/química
3.
Pak J Pharm Sci ; 36(5(Special)): 1677-1685, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38008967

RESUMO

Among the oral route, mouth dissolving tablets (MDTs) offer a benefit for drugs with slow dissolution and having low oral bioavailability. Epalrestat is one of the best effective diabetic neuropathy medication used for treating nerve pain. The problem associated with this drug is high first pass metabolism and low solubility in acidic media as well in basic media leads to short half-life, delayed dissolution and side effects. Therefore, the goal of the current work is to developed an epalrestat MDTs tablet that will provide quick drug dissolution and a quick onset of action for the treatment of nerve pain. MDTs of epalrestat were formulated by direct compression using natural superdis integrants obtained from the various sources such as fenugreek, gum karaya and banana powder. All of the pre- and post-compression parameter results were shown to be in accordance with established specifications. In comparison to other formulations of MDTs, formulation F3 with 15 mg (7.5%) of banana powder displayed a higher rate of dissolution. It was determined that epalrestat MDTs containing natural superdisintegrant were successfully formulated with acceptable physical and chemical properties, quick oral cavity disintegration, a quick onset of action and improved patient compliance.


Assuntos
Boca , Neuralgia , Humanos , Pós/química , Solubilidade , Comprimidos/química
4.
Molecules ; 27(6)2022 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-35335159

RESUMO

The present study aimed to develop a local dental nanoemulgel formulation of Nigella sativa oil (NSO) for the treatment of periodontal diseases. NSO purchased from a local market was characterized using a GC-MS technique. A nanoemulsion containing NSO was prepared and incorporated into a methylcellulose gel base to develop the nanoemulgel formulation. The developed formulation was optimized using a Box-Behnken statistical design (quadratic model) with 17 runs. The effects of independent factors, such as water, oil, and polymer concentrations, were studied on two dependent responses, pH and viscosity. The optimized formulation was further evaluated for droplet size, drug release, stability, and antimicrobial efficacy. The developed formulation had a pH of 7.37, viscosity of 2343 cp, and droplet size of 342 ± 36.6 nm. Sustained release of the drug from the gel for up to 8 h was observed, which followed Higuchi release kinetics with non-Fickian diffusion. The developed nanoemulgel formulation showed improved antimicrobial activity compared to the plain NSO. Given the increasing emergence of periodontal diseases and antimicrobial resistance, an effective formulation based on a natural antibacterial agent is warranted as a dental therapeutic agent.


Assuntos
Metilcelulose , Saúde Bucal , Emulsões/química , Óleos de Plantas
5.
Molecules ; 27(9)2022 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-35566287

RESUMO

The occurrence of fungal infections has increased over the past two decades. It is observed that superficial fungal infections are treated by conventional dosage forms, which are incapable of treating deep infections due to the barrier activity possessed by the stratum corneum of the skin. This is why the need for a topical preparation with advanced penetration techniques has arisen. This research aimed to encapsulate fluconazole (FLZ) in a novasome in order to improve the topical delivery. The novasomes were prepared using the ethanol injection technique and characterized for percent entrapment efficiency (EE), particle size (PS), zeta potential (ZP), drug release, Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), scanning electron microscopy (SEM) and antifungal activity. The FN7 formulation with 94.45% EE, 110 nm PS and -24 ZP proved to be the best formulation. The FN7 formulation showed a 96% release of FLZ in 8 h. FTIR showed the compatibility of FLZ with excipients and DSC studies confirmed the thermal stability of FLZ in the developed formulation. The FN7 formulation showed superior inhibition of the growth of Candida albicans compared to the FLZ suspension using a resazurin reduction assay, suggesting high efficacy in inhibiting fungal growth.


Assuntos
Fluconazol , Micoses , Antifúngicos/uso terapêutico , Candida albicans , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Fluconazol/química , Fluconazol/farmacologia , Micoses/tratamento farmacológico , Tamanho da Partícula
6.
Pak J Pharm Sci ; 35(4): 1135-1142, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36008912

RESUMO

The current studies were aimed to formulate ethyl cellulose (EC), beta-cyclodextrin (ß-CD facilitated EC based Ondansetron nanosponges (NS) using Response Surface Methodology (RSM) by employing One Factor Design. The NS were fabricated by Emulsion Solvent Diffusion method, followed by characterizations including, drug-polymer compatibility, entrapment efficiency, percentage yield, zeta size, zeta potential and in-vitro release of drug and Scanning Electron Microscopy (SEM) and X-Ray Diffractometry (XRD). The outcomes of Fourier Transformed Infra-Red Spectroscopy (FTIR) have confirmed the compatibility of the drug and excipients. It was found that NS have good entrapment efficiency along with their satisfactory percentage yield. Particle size analysis has confirmed the synthesis of nanosized NS (87.8nm to 108.2nm), having spongy surface, that was described by SEM results. Furthermore, the drug release studies have described a good sustained release of ondansetron for the period of 8 hours. The kinetic modeling has predicted that drug would follow the non fickian type of diffusion mechanism. The application of statistical approach was found helpful in designing and evaluating the NS, avoiding the laborious work, needs to be conducted while using hit and trial method.


Assuntos
Excipientes , Ondansetron , Portadores de Fármacos , Liberação Controlada de Fármacos , Tamanho da Partícula , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier
7.
Pak J Pharm Sci ; 35(4(Special)): 1229-1239, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36218102

RESUMO

Atherosclerotic patients suffering with acute coronary disease are lying at high risk. This life-threatening problem can be curtailed by using statins e.g., ezetimibe (EZT), atorvastatin calcium (ATC). In this study, co-loaded Fast Dissolving oral films (FDOFs), of ATC-EZT with HPMC E5 prepared by solvent evaporation method. Prepared FDOFs were evaluated for physicochemical, thermal and mechanical properties. In-vivo animal studies were performed on albino rats against diet induced hyperlipidemia. Prepared FDOFs have rapid DT; 27sec, TDT >2min and in-vitro drug release 97% in a min. In DSC, FTIR and XRD analysis, prepared films were chemically compatible and no chemical interaction of drugs and excipient was found. In kinetic modeling, it was observed their EZT exhibited lowest R2 value for zero order kinetic and best fit model was first order kinetic (n, 0.9823). The korsmeyer peppas model films (n, 0.016) indicate fickian type drug diffusion. The groups treated with marketed suspension of drug and FODPs were compared with normal group and high fats diet group. Study reviled that combination FDOPs of both ATC/EZT significantly reduce hyperlipemia as compared to high fat diet group. It can be concluded that ATC and EZT encapsulated in FODFs provide instant drug release and better therapeutic outcomes.


Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases , Hiperlipidemias , Animais , Atorvastatina , Excipientes/química , Ezetimiba/farmacologia , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hiperlipidemias/tratamento farmacológico , Solventes , Ratos
8.
Drug Dev Ind Pharm ; 47(8): 1335-1341, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34622736

RESUMO

OBJECTIVE: The goals of this study were to (1) delineate a technique to prepare stable aqueous vitamin E/Soluplus® dispersions; (2) characterize films cast from the aqueous dispersions; and (3) demonstrate the utility of the aqueous dispersions in fluid bed coating applications. This study demonstrated the feasibility of using vitamin E in the preparation of amphiphilic film withs potential use in delayed-release coating applications. METHODS: Low viscosity aqueous vitamin E/Soluplus® dispersions were prepared by first spray drying ethanolic vitamin E/Soluplus® solutions followed by high-shear homogenization of the solid dispersions in water. Concentrated (10%) aqueous dispersions containing 0%, 10%, 20%, and 30% of vitamin E in the binary blend with Soluplus® were then cast into films and characterized for contact angle and mechanical strength by texture analysis. RESULTS: All films were hydrophilic and homogenous, which confirmed the utility of vitamin E as a plasticizer for the Soluplus® polymer. The 0% and 10% films were brittle whereas the 30% were tacky. The 20% dispersion was subsequently used to coat acetaminophen granules by a fluidized bed process to a dry weight gain of 10-30%. When tested by a dissolution study, a delay in acetaminophen release was observed as a function of weight gain. CONCLUSION: The results from this study demonstrated that it is feasible to produce stable vitamin E/Soluplus® aqueous dispersions to be used as solvent-free functional film coating materials.


Assuntos
Acetaminofen , Vitamina E , Humanos , Polietilenoglicóis , Polivinil , Solubilidade , Água , Aumento de Peso
9.
Pharm Dev Technol ; 26(10): 1102-1109, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34645368

RESUMO

The objective of the present study was to investigate the feasibility of formulating and loading Curcumin SEDDS (Self-Emulsified Drug Delivery Systems) into films made from Soluplus® as the film-forming polymer. Films with up to 30% of Curcumin SEDDS were prepared by the solvent casting technique and analyzed for their mechanical and dissolution properties. A nine-run, two-factor, three-level factorial design was utilized to investigate the effect of SEDDS load (10, 20, and 30% w/w) and film thickness (10, 25, and 40 mils) on the tensile strength, elongation, and adhesiveness of the films. The dissolution profile of the films was also investigated by a USP Type 1 method. SEDDS loading was found to plasticize Soluplus® and to yield transparent films of good mechanical properties. Increasing SEDDS load, however, was found to reduce the tensile strength of the films, while increasing their adhesiveness and elongation. On the other hand, while an increase in film thickness was found to increase the tensile strength of the films, it reduced the elongation capacity of the films. Loading SEDDS into Soluplus® films was also found to sustain their release over 6 h, where a significant delay in release was found at lower SEDDS loads. This study demonstrated that Soluplus® can be used not only to formulate SEDDS into polymeric films but also to sustain their release over an extended time.


Assuntos
Curcumina , Preparações de Ação Retardada , Sistemas de Liberação de Medicamentos , Emulsões , Polietilenoglicóis , Polivinil , Solubilidade , Solventes
10.
ADMET DMPK ; 12(3): 431-462, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39091900

RESUMO

Background and purpose: Hair loss is a prevalent problem affecting millions of people worldwide, necessitating innovative and efficient regrowth approaches. Nanostructured lipid carriers (NLCs) have become a hopeful option for transporting bioactive substances to hair follicles because of their compatibility with the body and capability to improve drug absorption. Review approach: Recently, surface modification techniques have been used to enhance hair regeneration by improving the customization of NLCs. These techniques involve applying polymers, incorporating targeting molecules, and modifying the surface charge. Key results: The conversation focuses on how these techniques enhance stability, compatibility with the body, and precise delivery to hair follicles within NLCs. Moreover, it explains how surface-modified NLCs can improve the bioavailability of hair growth-promoting agents like minoxidil and finasteride. Furthermore, information on how surface-modified NLCs interact with hair follicles is given, uncovering their possible uses in treating hair loss conditions. Conclusion: This review discusses the potential of altering the surface of NLCs to customize them for enhanced hair growth. It offers important information for upcoming studies on hair growth.

12.
Front Pharmacol ; 15: 1433734, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39246659

RESUMO

Introduction: The study aimed to systematically enhance the fabrication process of flurbiprofen-loaded bilosomes (FSB) using Quality by Design (QbD) principles and Design of Experiments (DOE). The objective was to develop an optimized formulation with improved entrapment efficiency and targeted drug delivery capabilities. Methods: The optimization process involved applying QbD principles and DOE to achieve the desired formulation characteristics. Superparamagnetic iron oxide nanoparticles (SPIONs) were incorporated to impart magnetic responsiveness. The size, entrapment efficiency, morphology, and in vitro release patterns of the FSB formulation were evaluated. Additionally, an in situ forming hydrogel incorporating FSB was developed, with its gelation time and drug release kinetics assessed. In vivo studies were conducted on osteoarthritic rats to evaluate the efficacy of the FSB-loaded hydrogel. Results: The optimized FSB formulation yielded particles with a size of 453.60 nm and an entrapment efficiency of 91.57%. The incorporation of SPIONs enhanced magnetic responsiveness. Morphological evaluations and in vitro release studies confirmed the structural integrity and sustained release characteristics of the FSB formulation. The in situ forming hydrogel exhibited a rapid gelation time of approximately 40 ± 1.8 s and controlled drug release kinetics. In vivo studies demonstrated a 27.83% reduction in joint inflammation and an 85% improvement in locomotor activity in osteoarthritic rats treated with FSB-loaded hydrogel. Discussion: This comprehensive investigation highlights the potential of FSB as a promising targeted drug delivery system for the effective management of osteoarthritis. The use of QbD and DOE in the formulation process, along with the integration of SPIONs, resulted in an optimized FSB formulation with enhanced entrapment efficiency and targeted delivery capabilities. The in situ forming hydrogel further supported the formulation's applicability for injectable applications, providing rapid gelation and sustained drug release. The in vivo results corroborate the formulation's efficacy, underscoring its potential for improving the treatment of osteoarthritis.

13.
Eur J Pharm Biopharm ; 193: 28-43, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37858803

RESUMO

PURPOSE: The objective of the current research work was to fabricate a fosfestrol (FST)-loaded self-nanoemulsifying drug delivery system (SNEDDS) to escalate the oral solubility and bioavailability and thereby the effectiveness of FST against prostate cancer. METHODS: 32 full factorial design was employed, and the effect of lipid and surfactant mixtures on percentage transmittance, time required for self-emulsification, and drug release were studied. The optimized solid FST-loaded SNEDDS (FSTNE) was characterized for in vitro anticancer activity and Caco-2 cell permeability, and in vivo pharmacokinetic parameters. RESULTS: Using different ratios of surfactant and co-surfactant (Km) a pseudo ternary phase diagram was constructed. Thirteen liquid nano emulsion formulations (LNE-1 to LNE-13) were formulated at Km = 3:1. LNE-9 exhibited a higher % transmittance (99.25 ± 1.82 %) and a lower self-emulsification time (24 ± 0.32 s). No incompatibility was observed in FT-IR analysis. Within 20 min the solidified FST loaded LNE-9 (FSTNE) formulation showed almost complete drug release (98.20 ± 1.30 %) when compared to marketed formulation (40.36 ± 2.8 %), and pure FST (32 ± 3.3 %) in 0.1 N HCl. In pH 6.8 phosphate buffer, the release profiles are found moderately higher than in 0.1 N HCl. FSTNE significantly (P < 0.001) inhibited the PC-3 prostate cell proliferation and also caused apoptosis (P < 0.001) compared to FST. The in vitro Caco-2 cell permeability study results revealed 4.68-fold higher cell permeability of FSTNE than FST. Remarkably, 4.5-fold rise in bioavailability was observed after oral administration of FSTNE than plain FST. CONCLUSIONS: FSTNE remarkably enhanced the in vitro anticancer activity and Caco-2 cell permeability, and in vivo bioavailability of FST. Thus, FST-SNEDDS could be utilized as a potential carrier for effective oral treatment of prostate cancer.


Assuntos
Nanopartículas , Neoplasias da Próstata , Masculino , Humanos , Disponibilidade Biológica , Espectroscopia de Infravermelho com Transformada de Fourier , Células CACO-2 , Sistemas de Liberação de Medicamentos/métodos , Solubilidade , Liberação Controlada de Fármacos , Tensoativos/química , Administração Oral , Neoplasias da Próstata/tratamento farmacológico , Emulsões/química , Nanopartículas/química , Tamanho da Partícula
14.
J Control Release ; 353: 1150-1170, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36566843

RESUMO

Cancer ranks as the second foremost cause of death in various corners of the globe. The clinical uses of assorted anticancer therapeutics have been limited owing to the poor physicochemical attributes, pharmacokinetic performance, and lethal toxicities. Various sorts of co-crystals or nano co-crystals or co-crystals-laden nanocarriers have presented great promise in targeting cancer via improved physicochemical attributes, pharmacokinetic performance, and reduced toxicities. These systems have also demonstrated the controlled cargo release and passive targeting via enhanced permeation and retention (EPR) effect. In addition, regional delivery of co-crystals via inhalation and transdermal route displayed remarkable potential in targeting lung and skin cancer effectively. However, more research is required on the use of co-crystals in cancer and their commercialization. The present review mainly emphasizes co-crystals as emerging avenues in the treatment of various cancers by modulating the physicochemical and pharmacokinetic attributes of approved anticancer therapeutics. The worth of co-crystals in cancer treatment, computational paths in the co-crystals screening, diverse experimental techniques of co-crystals fabrication, and sorts of co-crystals and their noteworthy applications in targeting cancer are also discussed. Besides, the game changer approaches like nano co-crystals and co-crystals-laden nanocarriers, and co-crystals in regional delivery in cancer are also explained with reported case studies. Furthermore, regulatory directives for pharmaceutical co-crystals and their scale-up, and challenges are also highlighted with concluding remarks and future initiatives. In essence, co-crystals and nano co-crystals emerge to be a promising strategy in overwhelming cancers through improving anticancer efficacy, safety, patient compliance, and reducing the cost.


Assuntos
Sistemas de Liberação de Medicamentos , Neoplasias Cutâneas , Humanos , Sistemas de Liberação de Medicamentos/métodos , Portadores de Fármacos
15.
Pharmaceuticals (Basel) ; 16(4)2023 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-37111247

RESUMO

The current project was designed to prepare an oil-in-water (oil/water) hypericin nanoemulsion using eucalyptus oil for the preparation of an oil phase with chitosan as an emulsion stabilizer. The study might be a novelty in the field of pharmaceutical sciences, especially in the area of formulation development. Tween® 80 (Polysorbate) was used as the nonionic surfactant. The nanoemulsion was prepared by using the homogenization technique, followed by its physicochemical evaluation. The surface morphological studies showed the globular structure has a nano-sized diameter, as confirmed by zeta size analysis. The zeta potential analysis confirmed a positive surface charge that might be caused by the presence of chitosan in the formulation. The pH was in the range of 5.14 to 6.11, which could also be compatible with the range of nasal pH. The viscosity of the formulations was found to be affected by the concentration of chitosan (F1-11.61 to F4-49.28). The drug release studies showed that the presence of chitosan greatly influenced the drug release, as it was noticed that formulations having an elevated concentration of chitosan release lesser amounts of the drug. The persistent stress in the mouse model caused a variety of depressive- and anxiety-like behaviors that can be counteracted by chemicals isolated from plants, such as sulforaphane and tea polyphenols. In the behavioral test and source performance test, hypericin exhibited antidepressant-like effects. The results show that the mice treated for chronic mild stress had a considerably higher preference for sucrose after receiving continuous hypericin for 4 days (p = 0.0001) compared to the animals administered with normal saline (p ≤ 0.0001) as well as the naïve group (p ≤ 0.0001). In conclusion, prepared formulations were found to be stable and can be used as a potential candidate for the treatment of depression.

16.
J Biomol Struct Dyn ; : 1-12, 2023 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-37776007

RESUMO

The hepatitis C virus (HCV), which causes hepatitis C, is a viral infection that damages the liver and causes inflammation in the liver. New potentially effective antiviral drugs are required for its treatment owing to various issues associated with the existing medications, including moderate to severe adverse effects, higher costs, and the emergence of drug-resistant strains. The objective of the current study was to utilize computational techniques to assess the anti-HCV efficacy of certain phytochemicals against tetraspanin (CD81) and claudin 1 (CLDN1) entry proteins. A 200-nanosecond molecular dynamics (MD) simulation was employed to examine the stability of the lead-protein complexes. Free binding energy and molecular docking calculations were conducted utilizing MM/GBSA method, and the selectivity of hit compounds for CD81 and CLDN1 was determined. Five significant CD81 and CLDN1 inhibitors were identified: Petasiphenone, Silibinin, Tanshinone IIA, Taxifolin, and Topaquinone. The MM/GBSA analysis of the compounds revealed high free binding energies. All the identified compounds were stable within the CD81 and CLDN1 binding pockets. This study indicated the promising inhibitory potential of the identified compounds against CD81 and CLDN1 receptors and might develop into potential viral entry inhibitors. However, to validate the chemotherapeutic capabilities of the discovered leads extensive preclinical research is required.Communicated by Ramaswamy H. Sarma.

17.
Pharmaceuticals (Basel) ; 16(11)2023 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-38004417

RESUMO

A migraine is a condition of severe headaches, causing a disturbance in the daily life of the patient. The current studies were designed to develop immediate-release polymeric buccal films of Eletriptan Hydrobromide (EHBR) and Itopride Hydrochloride (ITHC) to improve their bioavailability and, hence, improve compliance with the patients of migraines and its associated symptoms. The prepared films were evaluated for various in vitro parameters, including surface morphology, mechanical strength, disintegration test (DT), total dissolving time (TDT), drug release and drug permeation, etc., and in vivo pharmacokinetic parameters, such as area under curve (AUC), mean residence time (MRT), half-life (t1/2), time to reach maximum concentration (Tmax), and time to reach maximum concentration (Cmax). The outcomes have indicated the successful preparation of the films, as SEM has confirmed the smooth surface and uniform distribution of drugs throughout the polymer matrix. The films were found to be mechanically stable as indicated by folding endurance studies. Furthermore, the optimized formulations showed a DT of 13 ± 1 s and TDT of 42.6 ± 0.75 s, indicating prompt disintegration as well as the dissolution of the films. Albino rabbits were used for in vivo pharmacokinetics, and the outcomes were evident of improved pharmacokinetics. The drug was found to rapidly permeate across the buccal mucosa, leading to increased bioavailability of the drug: Cmax of 130 and 119 ng/mL of ITHC and EHBR, respectively, as compared to 96 (ITHC) and 90 ng/mL (EHBR) of oral solution. The conclusion can be drawn that possible reasons for the enhanced bioavailability could be the increased surface area in the form of buccal films, its rapid disintegration, and faster dissolution, which led toward the rapid absorption of the drug into the blood stream.

18.
Polymers (Basel) ; 14(16)2022 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-36015575

RESUMO

Coating the solid dosage form, such as tablets, is considered common, but it is a critical process that provides different characteristics to tablets. It increases the value of solid dosage form, administered orally, and thus meets diverse clinical requirements. As tablet coating is a process driven by technology, it relies on advancements in coating techniques, equipment used for the coating process, evaluation of coated tablets, and coated material used. Although different techniques were employed for coating purposes, which may be based on the use of solvents or solvent-free, each of the methods used has its advantages and disadvantages, and the techniques need continued modification too. During the process of film coating, several inter-and intra-batch uniformity of coated material on the tablets is considered a critical point that ensures the worth of the final product, particularly for those drugs that contain an active medicament in the coating layer. Meanwhile, computational modeling and experimental evaluation were actively used to predict the impact of the operational parameters on the final product quality and optimize the variables in tablet coating. The efforts produced by computational modeling or experimental evaluation not only save cost in optimizing the coating process but also saves time. This review delivers a brief review on film coating in solid dosage form, which includes tablets, with a focus on the polymers and processes used in the coating. At the end, some pharmaceutical applications were also discussed.

19.
Drug Deliv ; 29(1): 1811-1823, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35666090

RESUMO

Self-emulsifying drug delivery systems (SEDDS) are a proven method for poorly soluble substances works by increasing the solubility and bioavailability. SEDDS and isotropic mixtures, are composed of oils, surfactants, and occasionally cosolvents. The ability of these formulations and methods to produce microemulsions or fine oil-in-water (o/w) emulsions after moderate stirring and dilution by water phase along the GI tract might be a promising technique for lipophilic agents with dissolution rate-limited absorption. This review provides an outline of SEDDS's numerous advances and biopharmaceutical elements, types, manufacturing, characterization, limitations, and future prospects. The evaluation of SEDDS and its applications are also discussed, focusing on the advances of SEDDS's solid self-emulsifying delivery mechanism and dosage form. By integrating suitable polymer into the formulation, SEDDS may be studied for the creation of a formulation with sustained drug release. This technology's improvement might lead to a new application in the field of medicine delivery. SEDDS has been demonstrated to be quite efficient in increasing oral bioavailability of lipophilic products. SEDDS is one of the promising methods for controlling the characteristics of medications that are not great choices for oral delivery. It is also worth mentioning that SEDDS may be made in variety of solid dosage forms that are acceptable for both oral and parenteral administration.


Assuntos
Sistemas de Liberação de Medicamentos , Água , Administração Oral , Disponibilidade Biológica , Sistemas de Liberação de Medicamentos/métodos , Emulsões , Solubilidade
20.
Pharmaceuticals (Basel) ; 15(7)2022 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-35890143

RESUMO

Over the past few decades, researchers and companies have been trying to develop novel drug delivery systems to ensure safety, efficacy, compliance, and patient acceptability. Nowadays drug discovery and development are expensive, complex, and time-consuming processes, but trends are moving toward novel drug delivery systems. This delivery system helps to achieve drug response by local and systemic action through different routes. This novel approach of preparing orodispersible films (ODFs) provides benefits to paediatric, geriatric, and bedridden patients. This review paper aims to provide details on the preparation, characterization, and evaluation of ODFs; it also aims to focus on the positive and negative factors that affect film formulation and give an insight into potential drug candidates and polymers for use in ODFs. ODFs are effective, safe, and have good bioavailability as compared to fast-disintegrating tablets. The novel approach has various advantages because it provides instant effects in emergency situations and in schizophrenic and dysphasic patients without the need for taking water, the films disintegrating within a few seconds in the oral cavity. The solvent casting method is the most frequently used technique to develop ODFs, using film-forming polymers, which have a fast disintegration time, improved drug dissolution, and better drug contents.

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