Recent advancements in drug delivery technologies utilizing a variety of carriers have resulted in a path-breaking revolution in the approach towards diagnosis and therapy alike in the current times. ...Need for materials with high thermal, chemical and mechanical properties have led to the development of mesoporous silica nanoparticles (MSNs). These ordered porous materials have garnered immense attention as drug carriers owing to their distinctive features over the others. They can be synthesized using a relatively simple process, thus making it cost effective. Moreover, by controlling the parameters during the synthesis; the morphology, pore size and volume and particle size can be transformed accordingly. Over the last few years, a rapid increase in research on MSNs as drug carriers for the treatment of various diseases has been observed indicating its potential benefits in drug delivery. Their widespread application for the loading of small molecules as well as macromolecules such as proteins, siRNA and so forth, has made it a versatile carrier. In the recent times, researchers have sorted to several modifications in the framework of MSNs to explore its potential in drug resistant chemotherapy, antimicrobial therapy. In this review, we have discussed the synthesis of these multitalented nanoparticles and the factors influencing the size and morphology of this wonder carrier. The second part of this review emphasizes on the applications and the advances made in the MSNs to broaden the spectrum of its use especially in the field of biomedicine. We have also touched upon the lacunae in the thorough understanding of its interaction with a biological system which poses a major hurdle in the passage of this carrier to the clinical level. In the final part of this review, we have discussed some of the major patents filed in the field of MSNs for therapeutic purpose.
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•Mesoporous Silica nanoparticles (MSNs) are highly explored as inorganic nanocarriers in therapy and diagnosis.•MSN-metal nanoparticles, MSN-quantum dots, MSN-carbon nanotubes, MSN- ...Fullerenes, MSN-graphenes/ graphene oxide, MSN- MSN-persistent luminescence nanoparticles and MSN-carbon dots have wide application.•MSN-based theranostic nanoconjugates and upconverted nanoparticles (UCNPs) are the future in theranostics.
The field of advanced nanotechnology is brimming with a plethora of nanotheranostics whose combinatorial synergistic applicability in treating malignant tumors is tremendous. But such multifunctional systems do hold drawbacks that are primarily liable to the inherent nature as well as the properties of the incorporated nanoparticles, which can be effectively tackled by either substituting or incorporating molecules having higher biocompatibility and biodegradability profiles. So, one such sort after, highly exploited inorganic nanocarrier using which theranostic platforms are developed is the Mesoporous Silica Nanoparticle (MSNs), whose amalgamation with upconversion nanoparticles having cutting-edge Near-Infrared imaging proficiency is gaining eminence in biomedicine-based research owing to its exemplary properties in drug targeting, bio-imaging and photodynamic/photothermal therapy, that makes them interesting for further research. MSNs are versatile in aspects related to their pore size and nature, greater drug loading efficiency, and functionalization accentuating their applicability. Several constructive studies with MSNs have been attempted by researchers worldwide, whose manipulation ultimately serves the said purpose of achieving a more holistic approach to treating carcinomas. This article principally sheds light on MSN-based hybrid nanotheranostics such as MSN-Metal Nanoparticles, MSN-Quantum Dots, MSN-Carbon Nanotubes, MSN-Fullerenes, MSN-Graphenes/ Graphene Oxide, MSN-Persistent Luminescence Nanoparticles, and MSN-Carbon-Dots, along with their designing strategies, characterization, applications, in vitro and in vivo efficacy, limitations, biotoxicity as well as the current challenges and future perspectives.
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•Novel hybrid nanostructures have multi-functional features.•Organic and inorganic hybrid nanostructures have renewed applications in nanomedicine.•Applications include combination ...chemotherapy, gene therapy, immunotherapy, imaging.
Hybrid nanostructures are nanocomposites constructed from at least two different types of materials to imbibe the individual advantages while overcoming individual shortcomings and forming one nanostructure with superior properties not possessed by single component nanostructures. Organic and inorganic hybrid nanostructures are a class of promising nanocomposites that possess interesting biological and physicochemical properties, making them highly attractive in biomedical applications. Recently, organic hybrid nanostructures such as hybrid lipid-based systems, hybrid polymeric nanoparticles, micelles, dendrimers and inorganic hybrid nanostructures such as metal nanoparticles, hybrid carbon nanomaterials, hollow mesoporous silica nanoparticles, hybrid magnetic nanoparticles and layered double hydroxides nanosheets and organic–inorganic hybrid nanostructures are developed for implementation in nanomedicine. Numerous studies have been conducted to investigate the employment of hybrid nanostructures in biomedical fields for gene therapy, chemotherapy, immunotherapy, combination chemotherapy, imaging platform, photodynamic and photothermal therapy. Novel hybrid nanostructures with multi-functional features have been evolved. This review summarizes the recent development and applications and directs the future perspective of hybrid nanostructures in biomedical applications.
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•Resveratrol loaded nanostructured lipid carriers (RVT-NLCs) for cancer therapy.•Local delivery of the NLCs were achieved using microneedle array systems (MN).•RVT-NLCs showed active ...uptake and lower IC50 in the breast cancer cell lines.•RVT-NLCs showed increased bioavailability when administered via MN.•Higher breast tissue localization of RVT was observed in RVT-NLCs administered via MN.
Resveratrol (RVT) is one of the potent anticancer phytochemicals which has shown promising potential for breast cancer therapy. However, its short half-life and low bioavailability is a major hurdle in its effective use. In this study, we have developed nanostructured lipid carriers (NLCs) of RVT to enable localized delivery of the drug to the breast tissues using microneedle arrays to improve effectiveness. The NLCs were optimized using the Design of Experiments approach and characterized for their particle size, polydispersity index, zeta potential and entrapment efficiency. The RVT-NLCs delivered using microneedle array 1200 showed a higher permeation of RVT across the skin with lower skin retention compared to pure RVT. Further, RVT-NLCs showed higher anticancer activity on MDA-MB-231 breast cancer cell lines and enhanced internalization compared to pure RVT. Moreover, the RVT-NLCs were found to inhibit the migration of MDA-MB-231 breast cancer cell lines. Preclinical studies in rats showed that RVT-NLCs delivered via microneedles demonstrated a remarkable increase in the Cmax, Tmax and AUC0-inf, and a higher localization in breast tissue compared to pure RVT administered orally. These results suggests that the RVT-NLCs administered by microneedle array system is an effective strategy for the local delivery of RVT for breast cancer therapy.
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Resveratrol (RVT) is a polyphenolic phytoestrogen which has shown antiproliferative activity in breast cancer. However, its low bioavailability and short half-life have restricted its ...use. The current study aimed to develop transdermal patches of RVT and evaluate its site-specific delivery for breast cancer therapy. Different penetration enhancers were screened using a computational tool, quantitative structure propery relationship (QSPR). The best permeation of RVT was observed in a patch comprising hydroxypropyl methylcellulose (HPMC) E15LV: HPMC-K4M: polyvinyl pyrrolidone (PVP) K30 in the ratio of 3:1:2 as release controlling polymers with Glycerol:Capryol 90 (4:1) as penetration enhancer and plasticizer. To assess the localized delivery of RVT, the patch was applied to the breast of female rats. Higher breast tissue disposition with lower systemic concentration was observed compared to oral administration, demonstrated by increased AUC and MRT. Further, the optimized RVT patches were tested in 7,12-Dimethylbenzaanthracene (DMBA) induced rat mammary cancer. Compared to oral RVT, the application of RVT tansdermal patches significantly reduced the tumor volume and serum CA 15–3, a cancer biomarker. Thus, the RVT transdermal patch may be a viable approach for ensuring high local concentration of drug for site-specific delivery in breast cancer therapy.
•Formulation design comprises complicated stages.•Formulation optimization requires an exhaustive experimental work.•Computational tools help in formulation properties prediction.•Computational ...approach reduces experimentation efforts and time taken in formulation design.
Formulation design is an important phase in the drug development process. However, this process at an experimental level requires exhaustive experimental work. Excipient selection, prediction of solubility, encapsulation efficiency, release patterns, drug absorption, stability, and mechanism of nanoparticle formation are some of the essential steps in formulation design. The use of various computational tools, including quantitative structure–activity relationships (QSARs), molecular modeling, molecular mechanics, discrete element modeling, finite element method, computational fluid dynamics, and physiologically based pharmacokinetics (PBPK) modeling, help in the identification of drug product inadequacies and to recommend avenues for understanding complex formulation design in less time with lower investment. Here, we focus on computational modeling tools used in formulation design and its applications.
The coronavirus disease (COVID-19) is spreading between human populations mainly through nasal droplets. Currently, the vaccines have great hope, but it takes years for testing its efficacy in human. ...As there is no specific drug treatment available for COVID-19 pandemic, we explored in silico repurposing of drugs with dual inhibition properties by targeting transmembrane serine protease 2 (TMPRSS2) and human angiotensin-converting enzyme 2 (ACE2) from FDA-approved drugs. The TMPRSS2 and ACE2 dual inhibitors in COVID-19 would be a novel antiviral class of drugs called “entry inhibitors.” For this purpose, approximately 2800 US-FDA approved drugs were docked using a virtual docking tool with the targets TMPRSS2 and ACE2. The best-fit drugs were selected as per docking scores and visual outcomes. Later on, drugs were selected on the basis of molecular dynamics simulations. The drugs alvimopan, arbekacin, dequalinum, fleroxacin, lopinavir, and valrubicin were shortlisted by visual analysis and molecular dynamics simulations. Among these, lopinavir and valrubicin were found to be superior in terms of dual inhibition. Thus, lopinavir and valrubicin have the potential of dual-target inhibition whereby preventing SARS-CoV-2 entry to the host. For repurposing of these drugs, further screening in vitro and in vivo would help in exploring clinically.
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•Dual inhibition by targeting TMPRSS2 and ACE2 from FDA-approved drugs by computational drug-repurposing.•Virtual screening by docking to TMPRSS2 (homology of 5TJX) and ACE2 (1R4L).•Shortlisted alvimopan, arbekacin, dequalinum, fleroxacin, lopinavir, and valrubicin.•Lopinavir and valrubicin were found superior in terms of dual inhibition.
•Use of computational modeling in drug solubility prediction is presented.•Computational theories related to solubility are discussed.•Applications of computational modeling in the solubility ...enhancement techniques are discussed.
Discovering new therapeutically active molecules is the ultimate destination in pharmaceutical research and development. Most drugs discovered are lipophilic and, hence, exhibit poor aqueous solubility, resulting in low bioavailability. Thus, there is a need to use various solubility enhancement techniques. Computational approaches enable the analysis of drug–carrier interactions or the numerous conformational changes in the carrier matrix that might establish an appropriate balance between cohesive and adhesive stability in a formulation. In this review, we discuss research approaches that provided molecular insight into drugs and their modifiers to unravel their solubility, stability, and bioavailability.
Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) induced Novel Coronavirus Disease (COVID-19) has currently become pandemic worldwide. Though drugs like remdesivir, favipiravir, and ...dexamethasone found beneficial for COVID-19 management, they have limitations clinically, and vaccine development takes a long time. The researchers have reported key proteins which could act as druggable targets. Among them, the major protease Mpro is first published, plays a prominent role in viral replication and an attractive drug-target for drug discovery. Hence, to target Mpro and inhibit it, we accomplished the virtual screening of US-FDA approved drugs using well-known drug repurposing approach by computer-aided tools.
The protein Mpro, PDB-ID 6LU7 was imported to Maestro graphical user interphase of Schrödinger software. The US-FDA approved drug structures are imported from DrugBank and docked after preliminary protein and ligand preparation. The drugs are shortlisted based on the docking scores in the Standard Precision method (SP-docking) and then based on the type of molecular interactions they are studied for molecular dynamics simulations.
The docking and molecular interactions studies, five drugs emerged as potential hits by forming hydrophilic, hydrophobic, electrostatic interactions. The drugs such as arbutin, terbutaline, barnidipine, tipiracil and aprepitant identified as potential hits. Among the drugs, tipiracil and aprepitant interacted with the Mpro consistently, and they turned out to be most promising.
This study shows the possible exploration for drug repurposing using computer-aided docking tools and the potential roles of tipiracil and aprepitant, which can be explored further in the treatment of COVID-19.
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The present paper is aimed at development of functionalized risperidone liposomes for brain targeting through nasal route for effective therapeutic management of schizophrenia. The risperidone ...liposomes were prepared by thin film hydration method. Various parameters such as lipid ratio and lipid to drug ratio were optimized by using Design-Expert® Software to obtain high entrapment with minimum vesicle size. The surface of the optimized liposomes was modified by coating stearylamine and MPEG-DSPE for enhanced penetration to the brain. The formulations were evaluated for vesicle size, zeta potential, and entrapment efficiency. The morphology was studied by Transmission Electron Microscopy (TEM). In vivo efficacy was assessed by performing pharmacokinetic study in Wistar albino rats following intranasal administration of the formulations in comparison to intravenous bolus administration of pure drug. The mean vesicle size of optimized liposomes ranged from 90 to 100nm with low polydispersity index (<0.5). The entrapment efficiency of optimized liposomes was between 50 and 60%, functionalized liposomes showed maximum entrapment. The TEM images showed predominantly spherical vesicles with smooth bilayered surface. All formulations showed prolonged diffusion controlled drug release. The in vivo results showed that liposomal formulations provided enhanced brain exposure. Among the formulations studied, PEGylated liposomes (LP-16) had shown greater uptake of risperidone into the brain than plasma. High brain targeting efficiency index for LP-16 indicating preferential transport of the drug to brain. The study demonstrated successful formulation of surface modified risperidone liposomes for nasal delivery with brain targeting potential.
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