Semi-Solid Pharmaceutical Formulations for the Delivery of Papain Nanoparticles

Papain is a therapeutic enzyme with restricted applications due to associated allergenic reactions. Papain nanoparticles have shown to be safe for biomedical use, although a method for proper drug loading and release remains to be developed. Thus, the objective of this work was to develop and assess the stability of papain nanoparticles in a prototype semi-solid formulation suitable for dermatological or topical administrations. Papain nanoparticles of 7.0 ± 0.1 nm were synthesized and loaded into carboxymethylcellulose- and poly(vinyl alcohol)-based gels. The formulations were then assayed for preliminary stability, enzyme activity, cytotoxicity studies, and characterized according to their microstructures and protein distribution. The formulations were suitable for papain nanoparticle loading and provided a stable environment for the nanoparticles. The enzyme distribution along the gel matrix was homogeneous for all the formulations, and the proteolytic activity was preserved after the gel preparation. Both gels presented a slow release of the papain nanoparticles for four days. Cell viability assays revealed no potential cytotoxicity, and the presence of the nanoparticles did not alter the microstructure of the gel. The developed systems presented a potential for biomedical applications, either as drug delivery systems for papain nanoparticles and/or its complexes.

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The Effect of Phase Transition Temperature on Therapeutic Efficacy of Liposomal Bortezomib

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520620666200101150640 ◽

2020 ◽

Vol 20 (6) ◽

pp. 700-708

Author(s):

Mitra Korani ◽

Sara Nikoofal-Sahlabadi ◽

Amin R. Nikpoor ◽

Solmaz Ghaffari ◽

Hossein Attar ◽

...

Keyword(s):

Side Effects ◽

Cell Line ◽

Therapeutic Efficacy ◽

Drug Loading ◽

Particle Diameter ◽

In Vitro Cytotoxicity ◽

Liposomal Formulations ◽

Cytotoxicity Studies ◽

Anti Tumor Activity

Aims: Here, three liposomal formulations of DPPC/DPPG/Chol/DSPE-mPEG2000 (F1), DPPC/DPPG/Chol (F2) and HSPC/DPPG/Chol/DSPE-mPEG2000 (F3) encapsulating BTZ were prepared and characterized in terms of their size, surface charge, drug loading, and release profile. Mannitol was used as a trapping agent to entrap the BTZ inside the liposomal core. The cytotoxicity and anti-tumor activity of formulations were investigated in vitro and in vivo in mice bearing tumor. Background: Bortezomib (BTZ) is an FDA approved proteasome inhibitor for the treatment of mantle cell lymphoma and multiple myeloma. The low solubility of BTZ has been responsible for the several side effects and low therapeutic efficacy of the drug. Encapsulating BTZ in a nano drug delivery system; helps overcome such issues. Among NDDSs, liposomes are promising diagnostic and therapeutic delivery vehicles in cancer treatment. Objective: Evaluating anti-tumor activity of bortezomib liposomal formulations. Methods: Data prompted us to design and develop three different liposomal formulations of BTZ based on Tm parameter, which determines liposomal stiffness. DPPC (Tm 41°C) and HSPC (Tm 55°C) lipids were chosen as variables associated with liposome rigidity. In vitro cytotoxicity assay was then carried out for the three designed liposomal formulations on C26 and B16F0, which are the colon and melanoma cancer mouse-cell lines, respectively. NIH 3T3 mouse embryonic fibroblast cell line was also used as a normal cell line. The therapeutic efficacy of these formulations was further assessed in mice tumor models. Result: MBTZ were successfully encapsulated into all the three liposomal formulations with a high entrapment efficacy of 60, 64, and 84% for F1, F2, and F3, respectively. The findings showed that liposomes mean particle diameter ranged from 103.4 to 146.8nm. In vitro cytotoxicity studies showed that liposomal-BTZ formulations had higher IC50 value in comparison to free BTZ. F2-liposomes with DPPC, having lower Tm of 41°C, showed much higher anti-tumor efficacy in mice models of C26 and B16F0 tumors compared to F3-HSPC liposomes with a Tm of 55°C. F2 formulation also enhanced mice survival compared with untreated groups, either in BALB/c or in C57BL/6 mice. Conclusion: Our findings indicated that F2-DPPC-liposomal formulations prepared with Tm close to body temperature seem to be effective in reducing the side effects and increasing the therapeutic efficacy of BTZ and merits further investigation.

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Functionalization of Gold Nanostars with Cationic β-Cyclodextrin-Based Polymer for Drug Co-Loading and SERS Monitoring

Pharmaceutics ◽

10.3390/pharmaceutics13020261 ◽

2021 ◽

Vol 13 (2) ◽

pp. 261

Author(s):

Orlando Donoso-González ◽

Lucas Lodeiro ◽

Álvaro E. Aliaga ◽

Miguel A. Laguna-Bercero ◽

Soledad Bollo ◽

...

Keyword(s):

Biomedical Applications ◽

Colloidal Stability ◽

Biomedical Application ◽

Drug Loading ◽

Gold Nanostars ◽

Raman Optical Activity ◽

Cationic Group ◽

Low Cytotoxicity ◽

Stability Limits ◽

Zeta Potential Analysis

Gold nanostars (AuNSs) exhibit modulated plasmon resonance and have a high SERS enhancement factor. However, their low colloidal stability limits their biomedical application as a nanomaterial. Cationic β-cyclodextrin-based polymer (CCD/P) has low cytotoxicity, can load and transport drugs more efficiently than the corresponding monomeric form, and has an appropriate cationic group to stabilize gold nanoparticles. In this work, we functionalized AuNSs with CCD/P to load phenylethylamine (PhEA) and piperine (PIP) and evaluated SERS-based applications of the products. PhEA and PIP were included in the polymer and used to functionalize AuNSs, forming a new AuNS-CCD/P-PhEA-PIP nanosystem. The system was characterized by UV–VIS, IR, and NMR spectroscopy, TGA, SPR, DLS, zeta potential analysis, FE-SEM, and TEM. Additionally, Raman optical activity, SERS analysis and complementary theoretical studies were used for characterization. Minor adjustments increased the colloidal stability of AuNSs. The loading capacity of the CCD/P with PhEA-PIP was 95 ± 7%. The physicochemical parameters of the AuNS-CCD/P-PhEA-PIP system, such as size and Z potential, are suitable for potential biomedical applications Raman and SERS studies were used to monitor PhEA and PIP loading and their preferential orientation upon interaction with the surface of AuNSs. This unique nanomaterial could be used for simultaneous drug loading and SERS-based detection.

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Polysaccharide-Based Aerogel Production for Biomedical Applications: A Comparative Review

Materials ◽

10.3390/ma14071631 ◽

2021 ◽

Vol 14 (7) ◽

pp. 1631

Author(s):

Mariangela Guastaferro ◽

Ernesto Reverchon ◽

Lucia Baldino

Keyword(s):

Tissue Regeneration ◽

Supercritical Co2 ◽

Biomedical Applications ◽

Freeze Drying ◽

Time Interval ◽

Comparative Review ◽

Biomedical Field ◽

Low Cytotoxicity ◽

Gel Preparation ◽

Cell Adhesion And Proliferation

A comparative analysis concerning bio-based gels production, to be used for tissue regeneration, has been performed in this review. These gels are generally applied as scaffolds in the biomedical field, thanks to their morphology, low cytotoxicity, and high biocompatibility. Focusing on the time interval 2015–2020, the production of 3D scaffolds of alginate, chitosan and agarose, for skin and bone regeneration, has mainly been investigated. Traditional techniques are critically reviewed to understand their limitations and how supercritical CO2-assisted processes could overcome these drawbacks. In particular, even if freeze-drying represents the most widespread drying technique used to produce polysaccharide-based cryogels, supercritical CO2-assisted drying effectively allows preservation of the nanoporous aerogel structure and removes the organic solvent used for gel preparation. These characteristics are essential for cell adhesion and proliferation.

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Semi-interpenetrating polymeric networks based on poly(dimethylsiloxane)-chitosan-poly(vinyl alcohol) crosslinked with genipin with possible use in biomedical applications

Journal of Materials Science ◽

10.1007/s10853-020-05683-3 ◽

2021 ◽

Vol 56 (9) ◽

pp. 5936-5955

Author(s):

J. A. Benítez-Martínez ◽

I. M. Garnica-Palafox ◽

G. Vázquez-Victorio ◽

M. Hautefeuille ◽

F. M. Sánchez-Arévalo

Keyword(s):

Vinyl Alcohol ◽

Biomedical Applications ◽

Poly Vinyl Alcohol ◽

Polymeric Networks ◽

Interpenetrating Polymeric Networks

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Evaluation of Semi-Solid-State Fermentation of Elaeocarpus serratus L. Leaves and Black Soymilk by Lactobacillus plantarum on Bioactive Compounds and Antioxidant Capacity

Foods ◽

10.3390/foods10040704 ◽

2021 ◽

Vol 10 (4) ◽

pp. 704

Author(s):

Chia-Yu Tsui ◽

Chun-Yao Yang

Keyword(s):

Solid State ◽

Lactobacillus Plantarum ◽

Solid State Fermentation ◽

Nutritional Supplement ◽

Antioxidant Power ◽

Glucosidase Activity ◽

Fermented Product ◽

Ferric Reducing Antioxidant Power ◽

Semi Solid ◽

The Stability

Elaeocarpus serratus L. leaves (EL) containing phenolic compounds and flavonoids, including myricitrin with pharmacological properties, could be valorized as nutritional additive in foods. In this study, the semi-solid-state fermentation of EL and black soymilk (BS) by Lactobacillus plantarum BCRC 10357 was investigated. Without adding EL in MRS medium, the β-glucosidase activity of L. plantarum quickly reduced to 2.33 ± 0.15 U/mL in 36 h of fermentation; by using 3% EL, the stability period of β-glucosidase activity was prolonged as 12.94 ± 0.69 U/mL in 12 h to 13.71 ± 0.94 in 36 h, showing positive response of the bacteria encountering EL. Using L. plantarum to ferment BS with 3% EL, the β-glucosidase activity increased to 23.78 ± 1.34 U/mL in 24 h, and in the fermented product extract (FPE), the content of myricitrin (2297.06 μg/g-FPE) and isoflavone aglycones (daidzein and genistein, 474.47 μg/g-FPE) at 48 h of fermentation were 1.61-fold and 1.95-fold of that before fermentation (at 0 h), respectively. Total flavonoid content, myricitrin, and ferric reducing antioxidant power in FPE using BS and EL were higher than that using EL alone. This study developed the potential fermented product of black soymilk using EL as a nutritional supplement with probiotics.

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Formulation and Stability Test of Lip Cream Preparation of Kenop Flower Ethanol Extract (Gomphrena globosa L.)

Journal of Pharmacological Research and Developments ◽

10.46610/jprd.2021.v03i02.008 ◽

2021 ◽

Vol 3 (2) ◽

Author(s):

Mevi Irianti Tonapa ◽

Rani Dewi Pratiwi ◽

Elsye Gunawan

Keyword(s):

Ph Value ◽

Ethanol Extract ◽

Stability Test ◽

Gomphrena Globosa ◽

Homogeneous Composition ◽

Semi Solid ◽

The Stability ◽

Ph Range ◽

Average Dispersion ◽

Brown Color

Kenop Flower (Gomphrena globosa L.) is used in the manufacture of lip cream because contains betacyanin pigments that function as color pigments. This study aims to determine the physical quality and stability of the lip cream preparation of the ethanol extract of kenop flower (Gomphrena globosa L.). This research was conducted experimentally, including the manufacture of lip cream formulations with ethanol extract of kenop flower (Gomphrena globosa L.) with a concentration of 10%. The results of the physical examination test for lip cream preparations for all preparations have a distinctive vanilla aroma with a semi-solid texture, F0 has ivory white color and F1-F3 has a brown color. The preparations had a homogeneous composition, average pH 6-7, had good greasing power, 5.0-5.8 average dispersion and 60.33-66.67 seconds average adhesion. The stability test carried out on day 28 found that all preparations were stable, had a distinctive vanilla aroma with a semi-solid texture, F0 had ivory white color and F1-F3 had a brown color. The preparation has a homogeneous composition; the average pH is 6-7. Where the lip cream formulas F1 and F3 decreased the pH value on the 28th day from 7 to 6 but tended to be stable and in the pH range that matched the lip pH. And there is no phase separation in all formulas.

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Photodynamic Treatment of Colorectal Cancer Using Chlorin e6-Loaded Poly(lactide-co-glycolide)- Based Nanoparticles

Journal of Biomedical Nanotechnology ◽

10.1166/jbn.2021.3170 ◽

2021 ◽

Vol 17 (10) ◽

pp. 1939-1950

Author(s):

Beibei Lin ◽

Xuegu Xu ◽

Xiaobi Zhang ◽

Yinfei Yu ◽

Xiaoling Wang

Keyword(s):

Colorectal Cancer ◽

Drug Loading ◽

Average Diameter ◽

Plga Nanoparticles ◽

Chlorin E6 ◽

Photodynamic Treatment ◽

Hct 116 ◽

Hct 116 Cells ◽

The Stability

We prepared poly(lactide-co-glycolide) (PLGA) encapsulated with chlorin e6 (Ce6) in an effort to increase the stability and efficiency of photosensitizers for photodynamic therapy (PDT). We determined that Ce6-loaded PLGA nanoparticles (PLGA-Ce6 NPs) had drug-loading efficiency of 5%. The efficiency of encapsulation was 82%, the zeta potential was- 25 mV, and the average diameter was 130 nm. The encapsulation of Ce6 in PLGA nanoparticles showed excellent stability. The nanoparticles exhibited sustained Ce6 release profiles with 50% released at the end of 3 days, whereas free Ce6 showed rapid release within 1 day. Ce6 release patterns were controlled by encapsulation into PLGA. The uptake of PLGA-Ce6 NPs was significantly enhanced by endocytosis in the first 8 hours in the HCT-116 cell line. An intracellular reactive oxygen species assay revealed the enhanced uptake of the nanoparticles. An in vitro anti-tumor activity assay showed that the PLGA-Ce6 NPs exhibited enhanced phototoxicity toward HCT-116 cells and a slightly lower IC50 value in HCT-116 cells than Ce6 solution alone. Exposure of HCT-116 cell spheroids to PLGA-Ce6 NPs penetrated more profoundly and had better phototoxicity than pure drugs. These findings suggest that PLGA-Ce6 NPs might serve as PDT for colorectal cancer.

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Nanosuspensions – An Update on Recent Patents, Methods of Preparation, and Evaluation Parameters

Recent Patents on Nanotechnology ◽

10.2174/1872210514666201224103010 ◽

2020 ◽

Vol 14 ◽

Author(s):

Harpreet Kaur Khanuja ◽

Rajendra Awasthi ◽

Meenu Mehta ◽

Saurabh Satija ◽

Alaa AA Aljabali ◽

...

Keyword(s):

Drug Loading ◽

Pharmaceutical Research ◽

Vital Role ◽

Solid Matrix ◽

Colloidal Systems ◽

Passive Targeting ◽

Physico Chemical ◽

Extensive Information ◽

The Stability ◽

Preparation And Evaluation

Background: Nanosuspensions are colloidal systems consisting of pure drug and stabilizers, without matrix or lyophilized into a solid matrix. Nanosuspensions improve the solubility of the drug both in the aqueous and organic phases. Nanosuspensions are also known as brick dust molecules, as they increase the dissolution of a system and improve absorption. Methods: Extensive information related to nanosuspensions and its associated patents were collected using PubMed and Google Scholar. Results: Over the last decade nanosuspensions have attracted tremendous interest in pharmaceutical research. It provides unique features including, improved solubility, high drug loading capacity, and passive targeting. These particles are costeffective, simple, and have lesser side effects with minimal dose requirements. However, the stability of nanosuspensions still warrants attention. Conclusion: Nanosuspensions plays a vital role in handling the numerous drug entities with difficult physico-chemical characteristics such as solubility and can further aid with a range of routes that include nasal, transdermal, occular, parenteral, pulmonary etc. This review highlights the relevance of nanosuspensions in achieving safe, effective and targeted drug delivery.

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Extracellular Vesicles: “Stealth Transport Aircrafts” for Drugs

10.5772/intechopen.94502 ◽

2020 ◽

Author(s):

Chunying Liu ◽

Xuejing Lin ◽

Changqing Su

Keyword(s):

Extracellular Vesicles ◽

Drug Carrier ◽

Drug Loading ◽

Source Material ◽

Material Transport ◽

Disease Treatment ◽

Small Molecule Drugs ◽

Viral Particles ◽

The Stability

Extracellular vesicles (EVs) can deliver many types of drugs with their natural source material transport properties, inherent long-term blood circulation capabilities and excellent biocompatibility, and have great potential in the field of drug carrier. Modification of the content and surface of EVs according to the purpose of treatment has become a research focus to improve the drug load and the targeting of EVs. EVs can maximize the stability of the drugs, prevent immune clearance and achieve accurate delivery. Therefore, EVs can be described as \" stealth transport aircrafts \" for drugs. This chapter will respectively introduce the application of natural EVs as cell substitutes in cell therapy and engineered EVs as carriers of nucleic acids, proteins, small molecule drugs and therapeutic viral particles in disease treatment. It will also explain the drug loading and modification strategies of EVs, the source and characteristics of EVs. In addition, the commercialization progress of EVs drugs will be mentioned here, and the problems in their applications will be discussed in conjunction with the application of EVs in the treatment of COVID-19.

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Introduction of Surface Loops as a Tool for Encapsulin Functionalization.

10.1101/2021.05.13.444092 ◽

2021 ◽

Author(s):

Sandra Michel-Souzy ◽

Naomi M. Hamelmann ◽

Sara Zarzuela-Pura ◽

Jos M. J. Paulusse ◽

Jeroen J. L. M. Cornelissen

Keyword(s):

Biomedical Applications ◽

Large Scale ◽

Thermotoga Maritima ◽

Scale Production ◽

Structure Property ◽

Protein Subunit ◽

Protein Cages ◽

Notable Increase ◽

The Stability ◽

Surface Loops

Encapsulin based protein cages are nanoparticles with different biomedical applications, such as targeted drug delivery or imaging agents. These particles are biocompatible and can be produced in bacteria, allowing large scale production and protein engineering. In order to use these bacterial nanocages in different applications, it is important to further explore the potential of their surface modification and optimize their production. In this study we design and show new surface modifications of the Thermotoga maritima (Tm) and Brevibacterium linens (Bl) encapsulins. Two new loops on Tm encapsulin with a His-tag insertion after the residue 64 and the residue 127, and the modification of the C-terminal on Bl encapsulin, are reported. The multi-modification of the Tm encapsulin enables up to 240 different functionalities on the cage surface, resulting from 4 potential modifications per protein subunit. We furthermore report an improved protocol giving a better stability and providing a notable increase of the production yield of the cages. Finally, we tested the stability of different encapsulin variants over a year and the results show a difference in stability arising from the tag insertion position. These first insights in the structure-property relationship of encapsulins, with respect to the position of a function loop, allow for further study of the use of these protein nanocages in biomedical applications.

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