Simple Equations Pertaining to the Particle Number and Surface Area of Metallic, Polymeric, Lipidic and Vesicular Nanocarriers

Introduction: Bioactive encapsulation and drug delivery systems have already found their way to the market as efficient therapeutics to combat infections, viral diseases and different types of cancer. The fields of food fortification, nutraceutical supplementation and cosmeceuticals have also been getting the benefit of encapsulation technologies. Aim: Successful formulation of such therapeutic and nutraceutical compounds requires thorough analysis and assessment of certain characteristics including particle number and surface area without the need to employ sophisticated analytical techniques. Solution: Here we present simple mathematical formulas and equations used in the research and development of drug delivery and controlled release systems employed for bioactive encapsulation and targeting the sites of infection and cancer in vitro and in vivo. Systems covered in this entry include lipidic vesicles, polymeric capsules, metallic particles as well as surfactant- and tocopherol-based micro- and nanocarriers.

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Hydrogels as Drug Delivery Systems: A Review of Current Characterization and Evaluation Techniques

Pharmaceutics ◽

10.3390/pharmaceutics12121188 ◽

2020 ◽

Vol 12 (12) ◽

pp. 1188

Author(s):

Margaux Vigata ◽

Christoph Meinert ◽

Dietmar W. Hutmacher ◽

Nathalie Bock

Keyword(s):

Drug Delivery ◽

Drug Release ◽

Drug Delivery Systems ◽

Analytical Techniques ◽

Delivery Systems ◽

Local Drug Delivery ◽

Experimental Conditions ◽

In Vivo Models

Owing to their tunable properties, controllable degradation, and ability to protect labile drugs, hydrogels are increasingly investigated as local drug delivery systems. However, a lack of standardized methodologies used to characterize and evaluate drug release poses significant difficulties when comparing findings from different investigations, preventing an accurate assessment of systems. Here, we review the commonly used analytical techniques for drug detection and quantification from hydrogel delivery systems. The experimental conditions of drug release in saline solutions and their impact are discussed, along with the main mathematical and statistical approaches to characterize drug release profiles. We also review methods to determine drug diffusion coefficients and in vitro and in vivo models used to assess drug release and efficacy with the goal to provide guidelines and harmonized practices when investigating novel hydrogel drug delivery systems.

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Recent In Vitro and In Silico Advances in the Understanding of Intranasal Drug Delivery

Current Pharmaceutical Design ◽

10.2174/1381612826666201112143230 ◽

2020 ◽

Vol 26 ◽

Author(s):

John Chen ◽

Andrew Martin ◽

Warren H. Finlay

Keyword(s):

Drug Delivery ◽

In Silico ◽

Local Drug Delivery ◽

In Vivo Studies ◽

Intranasal Drug Delivery ◽

Nasal Sprays ◽

In Silico Studies ◽

Drug Delivery Devices

Background: Many drugs are delivered intranasally for local or systemic effect, typically in the form of droplets or aerosols. Because of the high cost of in vivo studies, drug developers and researchers often turn to in vitro or in silico testing when first evaluating the behavior and properties of intranasal drug delivery devices and formulations. Recent advances in manufacturing and computer technologies have allowed for increasingly realistic and sophisticated in vitro and in silico reconstructions of the human nasal airways. Objective: To perform a summary of advances in understanding of intranasal drug delivery based on recent in vitro and in silico studies. Conclusion: The turbinates are a common target for local drug delivery applications, and while nasal sprays are able to reach this region, there is currently no broad consensus across the in vitro and in silico literature concerning optimal parameters for device design, formulation properties and patient technique which would maximize turbinate deposition. Nebulizers are able to more easily target the turbinates, but come with the disadvantage of significant lung deposition. Targeting of the olfactory region of the nasal cavity has been explored for potential treatment of central nervous system conditions. Conventional intranasal devices, such as nasal sprays and nebulizers, deliver very little dose to the olfactory region. Recent progress in our understanding of intranasal delivery will be useful in the development of the next generation of intranasal drug delivery devices.

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In vitro Lipolysis as a Tool for the Establishment of IVIVC for Lipid-Based Drug Delivery Systems

Current Drug Delivery ◽

10.2174/1567201816666190620115716 ◽

2019 ◽

Vol 16 (8) ◽

pp. 688-697

Author(s):

Ravinder Verma ◽

Deepak Kaushik

Keyword(s):

Drug Delivery ◽

Ph Value ◽

Electron Paramagnetic Resonance Spectroscopy ◽

Rapid Screening ◽

Resonance Spectroscopy ◽

Fed State ◽

In Vitro Lipolysis ◽

Ph Stat

: In vitro lipolysis has emerged as a powerful tool in the development of in vitro in vivo correlation for Lipid-based Drug Delivery System (LbDDS). In vitro lipolysis possesses the ability to mimic the assimilation of LbDDS in the human biological system. The digestion medium for in vitro lipolysis commonly contains an aqueous buffer media, bile salts, phospholipids and sodium chloride. The concentrations of these compounds are defined by the physiological conditions prevailing in the fasted or fed state. The pH of the medium is monitored by a pH-sensitive electrode connected to a computercontrolled pH-stat device capable of maintaining a predefined pH value via titration with sodium hydroxide. Copenhagen, Monash and Jerusalem are used as different models for in vitro lipolysis studies. The most common approach used in evaluating the kinetics of lipolysis of emulsion-based encapsulation systems is the pH-stat titration technique. This is widely used in both the nutritional and the pharmacological research fields as a rapid screening tool. Analytical tools for the assessment of in vitro lipolysis include HPLC, GC, HPTLC, SEM, Cryo TEM, Electron paramagnetic resonance spectroscopy, Raman spectroscopy and Nanoparticle Tracking Analysis (NTA) for the characterization of the lipids and colloidal phases after digestion of lipids. Various researches have been carried out for the establishment of IVIVC by using in vitro lipolysis models. The current publication also presents an updated review of various researches in the field of in vitro lipolysis.

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Novel Phospholipid-Based Labrasol Nanomicelles Loaded Flavonoids for Oral Delivery with Enhanced Penetration and Anti-Brain Tumor Efficiency

Current Drug Delivery ◽

10.2174/1567201817666200210120950 ◽

2020 ◽

Vol 17 (3) ◽

pp. 229-245

Author(s):

Gang Wang ◽

Junjie Wang ◽

Rui Guan

Keyword(s):

Drug Delivery ◽

Brain Tumor ◽

Oral Delivery ◽

Safe Delivery ◽

Drug Delivery Vehicles ◽

Therapeutic Benefits ◽

Delivery Vehicles ◽

The Brain

Background: Owing to the rich anticancer properties of flavonoids, there is a need for their incorporation into drug delivery vehicles like nanomicelles for safe delivery of the drug into the brain tumor microenvironment. Objective: This study, therefore, aimed to prepare the phospholipid-based Labrasol/Pluronic F68 modified nano micelles loaded with flavonoids (Nano-flavonoids) for the delivery of the drug to the target brain tumor. Methods: Myricetin, quercetin and fisetin were selected as the initial drugs to evaluate the biodistribution and acute toxicity of the drug delivery vehicles in rats with implanted C6 glioma tumors after oral administration, while the uptake, retention, release in human intestinal Caco-2 cells and the effect on the brain endothelial barrier were investigated in Human Brain Microvascular Endothelial Cells (HBMECs). Results: The results demonstrated that nano-flavonoids loaded with myricetin showed more evenly distributed targeting tissues and enhanced anti-tumor efficiency in vivo without significant cytotoxicity to Caco-2 cells and alteration in the Trans Epithelial Electric Resistance (TEER). There was no pathological evidence of renal, hepatic or other organs dysfunction after the administration of nanoflavonoids, which showed no significant influence on cytotoxicity to Caco-2 cells. Conclusion: In conclusion, Labrasol/F68-NMs loaded with MYR and quercetin could enhance antiglioma effect in vitro and in vivo, which may be better tools for medical therapy, while the pharmacokinetics and pharmacodynamics of nano-flavonoids may ensure optimal therapeutic benefits.

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Controllable Drug Delivery by Na+/K+ ATPase α1 Targeting Peptide Conjugated DSPE-PEG Nanocarriers for Breast Cancer

Technology in Cancer Research & Treatment ◽

10.1177/15330338211027898 ◽

2021 ◽

Vol 20 ◽

pp. 153303382110278

Author(s):

Yayan Yang ◽

Qian Feng ◽

Chuanfeng Ding ◽

Wei Kang ◽

Xiufeng Xiao ◽

...

Keyword(s):

Breast Cancer ◽

Drug Delivery ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Click Reaction ◽

Chemotherapy Drugs ◽

Targeting Peptide ◽

And Migration

Although Epirubicin (EPI) is a commonly used anthracycline for the treatment of breast cancer in clinic, the serious side effects limit its long-term administration including myelosuppression and cardiomyopathy. Nanomedicines have been widely utilized as drug delivery vehicles to achieve precise targeting of breast cancer cells. Herein, we prepared a DSPE-PEG nanocarrier conjugated a peptide, which targeted the breast cancer overexpression protein Na+/K+ ATPase α1 (NKA-α1). The nanocarrier encapsulated the EPI and grafted with the NKA-α1 targeting peptide through the click reaction between maleimide and thiol groups. The EPI was slowly released from the nanocarrier after entering the breast cancer cells with the guidance of the targeting NKA-α1 peptide. The precise and controllable delivery and release of the EPI into the breast cancer cells dramatically inhibited the cells proliferation and migration in vitro and suppressed the tumor volume in vivo. These results demonstrate significant prospects for this nanocarrier as a promising platform for numerous chemotherapy drugs.

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Newly Emerging Airborne Pollutants: Current Knowledge of Health Impact of Micro and Nanoplastics

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18062997 ◽

2021 ◽

Vol 18 (6) ◽

pp. 2997

Author(s):

Alessio Facciolà ◽

Giuseppa Visalli ◽

Marianna Pruiti Ciarello ◽

Angela Di Pietro

Keyword(s):

Surface Area ◽

Current Knowledge ◽

Oxidative Degradation ◽

Health Impact ◽

Outdoor Exposure ◽

Environmental Matrices ◽

Potential Health ◽

Bodily Fluids

Plastics are ubiquitous persistent pollutants, forming the most representative material of the Anthropocene. In the environment, they undergo wear and tear (i.e., mechanical fragmentation, and slow photo and thermo-oxidative degradation) forming secondary microplastics (MPs). Further fragmentation of primary and secondary MPs results in nanoplastics (NPs). To assess potential health damage due to human exposure to airborne MPs and NPs, we summarize the evidence collected to date that, however, has almost completely focused on monitoring and the effects of airborne MPs. Only in vivo and in vitro studies have assessed the toxicity of NPs, and a standardized method for their analysis in environmental matrices is still missing. The main sources of indoor and outdoor exposure to these pollutants include synthetic textile fibers, rubber tires, upholstery and household furniture, and landfills. Although both MPs and NPs can reach the alveolar surface, the latter can pass into the bloodstream, overcoming the pulmonary epithelial barrier. Despite the low reactivity, the number of surface area atoms per unit mass is high in MPs and NPs, greatly enhancing the surface area for chemical reactions with bodily fluids and tissue in direct contact. This is proven in polyvinyl chloride (PVC) and flock workers, who are prone to persistent inflammatory stimulation, leading to pulmonary fibrosis or even carcinogenesis.

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Therapeutic effects of EGF-modified curcumin/chitosan nano-spray on wound healing

Regenerative Biomaterials ◽

10.1093/rb/rbab009 ◽

2021 ◽

Vol 8 (2) ◽

Author(s):

Yue Li ◽

QingQing Leng ◽

XianLun Pang ◽

Huan Shi ◽

YanLin Liu ◽

...

Keyword(s):

Drug Delivery ◽

Wound Healing ◽

Chitosan Nanoparticles ◽

Skin Lesions ◽

In Vitro Assays ◽

Therapeutic Effects ◽

Skin Defects ◽

Post Operation

Abstract Dermal injury, including trauma, surgical incisions, and burns, remain the most prevalent socio-economical health care issue in the clinic. Nanomedicine represents a reliable administration strategy that can promote the healing of skin lesions, but the lack of effective drug delivery methods can limit its effectiveness. In this study, we developed a novel nano-drug delivery system to treat skin defects through spraying. We prepared curcumin-loaded chitosan nanoparticles modified with epidermal growth factor (EGF) to develop an aqueous EGF-modified spray (EGF@CCN) for the treatment of dermal wounds. In vitro assays showed that the EGF@CCN displayed low cytotoxicity, and that curcumin was continuously and slowly released from the EGF@CCN. In vivo efficacy on wound healing was then evaluated using full-thickness dermal defect models in Wistar rats, showing that the EGF@CCN had significant advantages in promoting wound healing. On day 12 post-operation, skin defects in the rats of the EGF@CCN group were almost completely restored. These effects were related to the activity of curcumin and EGF on skin healing, and the high compatibility of the nano formulation. We therefore conclude that the prepared nano-scaled EGF@CCN spray represents a promising strategy for the treatment of dermal wounds.

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Mechanisms and Pharmaceutical Action of Lipid Nanoformulation of Natural Bioactive Compounds as Efficient Delivery Systems in the Therapy of Osteoarthritis

Pharmaceutics ◽

10.3390/pharmaceutics13081108 ◽

2021 ◽

Vol 13 (8) ◽

pp. 1108

Author(s):

Oana Craciunescu ◽

Madalina Icriverzi ◽

Paula Ecaterina Florian ◽

Anca Roseanu ◽

Mihaela Trif

Keyword(s):

Drug Delivery ◽

Bioactive Compounds ◽

Targeted Delivery ◽

Drug Delivery Systems ◽

Delivery Systems ◽

Joint Disease ◽

Duration Of Action ◽

Immune System Activation

Osteoarthritis (OA) is a degenerative joint disease. An objective of the nanomedicine and drug delivery systems field is to design suitable pharmaceutical nanocarriers with controllable properties for drug delivery and site-specific targeting, in order to achieve greater efficacy and minimal toxicity, compared to the conventional drugs. The aim of this review is to present recent data on natural bioactive compounds with anti-inflammatory properties and efficacy in the treatment of OA, their formulation in lipid nanostructured carriers, mainly liposomes, as controlled release systems and the possibility to be intra-articularly (IA) administered. The literature regarding glycosaminoglycans, proteins, polyphenols and their ability to modify the cell response and mechanisms of action in different models of inflammation are reviewed. The advantages and limits of using lipid nanoformulations as drug delivery systems in OA treatment and the suitable route of administration are also discussed. Liposomes containing glycosaminoglycans presented good biocompatibility, lack of immune system activation, targeted delivery of bioactive compounds to the site of action, protection and efficiency of the encapsulated material, and prolonged duration of action, being highly recommended as controlled delivery systems in OA therapy through IA administration. Lipid nanoformulations of polyphenols were tested both in vivo and in vitro models that mimic OA conditions after IA or other routes of administration, recommending their clinical application.

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Single Domain Antibodies as Carriers for Intracellular Drug Delivery: A Proof of Principle Study

Biomolecules ◽

10.3390/biom11070927 ◽

2021 ◽

Vol 11 (7) ◽

pp. 927

Author(s):

Sebas D. Pronk ◽

Erik Schooten ◽

Jurgen Heinen ◽

Esra Helfrich ◽

Sabrina Oliveira ◽

...

Keyword(s):

Drug Delivery ◽

Targeted Delivery ◽

Single Domain ◽

Drug Conjugates ◽

Intracellular Drug Delivery ◽

Internalization Rate ◽

Single Domain Antibodies ◽

Different Characteristics

Antibody-drug conjugates (ADCs) are currently used for the targeted delivery of drugs to diseased cells, but intracellular drug delivery and therefore efficacy may be suboptimal because of the large size, slow internalization and ineffective intracellular trafficking of the antibody. Using a phage display method selecting internalizing phages only, we developed internalizing single domain antibodies (sdAbs) with high binding affinity to rat PDGFRβ, a receptor involved in different types of diseases. We demonstrate that these constructs have different characteristics with respect to internalization rates but all traffic to lysosomes. To compare their efficacy in targeted drug delivery, we conjugated the sdAbs to a cytotoxic drug. The conjugates showed improved cytotoxicity correlating to their internalization speed. The efficacy of the conjugates was inhibited in the presence of vacuolin-1, an inhibitor of lysosomal maturation, suggesting lysosomal trafficking is needed for efficient drug release. In conclusion, sdAb constructs with different internalization rates can be designed against the same target, and sdAbs with a high internalization rate induce more cell killing than sdAbs with a lower internalization rate in vitro. Even though the overall efficacy should also be tested in vivo, sdAbs are particularly interesting formats to be explored to obtain different internalization rates.

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Surface-Initiated Atom Transfer Polymerized Anionic Corona on Gold Nanoparticles for Anti-Cancer Therapy

Pharmaceutics ◽

10.3390/pharmaceutics12030261 ◽

2020 ◽

Vol 12 (3) ◽

pp. 261

Author(s):

Wei Mao ◽

Sol Lee ◽

Ji Un Shin ◽

Hyuk Sang Yoo

Keyword(s):

Gold Nanoparticles ◽

Transfection Efficiency ◽

Cancer Therapeutics ◽

Atom Transfer ◽

Layer By Layer ◽

Dependent Manner ◽

Metallic Particles ◽

Anti Cancer

Surface initiated atom transfer radical polymerization (SI-ATRP) documented a simple but efficient technique to grow a dense polymer layer on any surface. Gold nanoparticles (AuNPs) give a broad surface to immobilize sulfhyryl group-containing initiators for SI-ATRP; in addition, AuNPs are the major nanoparticulate carriers for delivery of anti-cancer therapeutics, since they are biocompatible and bioinert. In this work, AuNPs with a disulfide initiator were polymerized with sulfoethyl methacrylate by SI-ATRP to decorate the particles with anionic corona, and branched polyethyeleneimine (PEI) and siRNA were sequentially layered onto the anionic corona of AuNP by electrostatic interaction. The in vitro anti-cancer effect confirmed that AuNP with anionic corona showed higher degrees of apoptosis as well as suppression of the oncogene expression in a siRNA dose-dependent manner. The in vivo study of tumor-bearing nude mice revealed that mice treated with c-Myc siRNA-incorporated AuNPs showed dramatically decreased tumor size in comparison to those with free siRNA for 4 weeks. Furthermore, histological examination and gene expression study revealed that the decorated AuNP significantly suppressed c-Myc expression. Thus, we envision that the layer-by-layer assembly on the anionic brushes can be potentially used to incorporate nucleic acids onto metallic particles with high transfection efficiency.

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