Research

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22 pages, 7845 KiB

Open AccessArticle

Influence of Folate-Targeted Gold Nanoparticles on Subcellular Localization and Distribution into Lysosomes

by Raffaella Daniele, Chiara Brazzale, Busra Arpac, Francesco Tognetti, Cristiano Pesce, Alessio Malfanti, Edward Sayers, Francesca Mastrotto, Arwyn T. Jones, Stefano Salmaso and Paolo Caliceti

Pharmaceutics 2023, 15(3), 864; https://doi.org/10.3390/pharmaceutics15030864 - 07 Mar 2023

Cited by 4 | Viewed by 1741

Abstract

The cell interaction, mechanism of cell entry and intracellular fate of surface decorated nanoparticles are known to be affected by the surface density of targeting agents. However, the correlation between nanoparticles multivalency and kinetics of the cell uptake process and disposition of intracellular [...] Read more.

The cell interaction, mechanism of cell entry and intracellular fate of surface decorated nanoparticles are known to be affected by the surface density of targeting agents. However, the correlation between nanoparticles multivalency and kinetics of the cell uptake process and disposition of intracellular compartments is complicated and dependent on a number of physicochemical and biological parameters, including the ligand, nanoparticle composition and colloidal properties, features of targeted cells, etc. Here, we have carried out an in-depth investigation on the impact of increasing folic acid density on the kinetic uptake process and endocytic route of folate (FA)-targeted fluorescently labelled gold nanoparticles (AuNPs). A set of AuNPs (15 nm mean size) produced by the Turkevich method was decorated with 0–100 FA-PEG_3.5kDa-SH molecules/particle, and the surface was saturated with about 500 rhodamine-PEG_2kDa-SH fluorescent probes. In vitro studies carried out using folate receptor overexpressing KB cells (KB^FR-high) showed that the cell internalization progressively increased with the ligand surface density, reaching a plateau at 50:1 FA-PEG_3.5kDa-SH/particle ratio. Pulse-chase experiments showed that higher FA density (50 FA-PEG_3.5kDa-SH molecules/particle) induces more efficient particle internalization and trafficking to lysosomes, reaching the maximum concentration in lysosomes at 2 h, than the lower FA density of 10 FA-PEG_3.5kDa-SH molecules/particle. Pharmacological inhibition of endocytic pathways and TEM analysis showed that particles with high folate density are internalized predominantly by a clathrin-independent process. Full article

(This article belongs to the Special Issue Special Issue in Honor of Professor Carla Caramella)

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14 pages, 5064 KiB

Open AccessEditor’s ChoiceArticle

Clay-Based Hydrogels as Drug Delivery Vehicles of Curcumin Nanocrystals for Topical Application

by Marco Ruggeri, Rita Sánchez-Espejo, Luca Casula, Raquel de Melo Barbosa, Giuseppina Sandri, Maria Cristina Cardia, Francesco Lai and César Viseras

Pharmaceutics 2022, 14(12), 2836; https://doi.org/10.3390/pharmaceutics14122836 - 17 Dec 2022

Cited by 7 | Viewed by 2014

Abstract

The poor water solubility of a significant number of active pharmaceutical ingredients (API) remains one of the main challenges in the drug development process, causing low bioavailability and therapeutic failure of drug candidates. Curcumin is a well-known Biopharmaceutics Classification System (BCS) class IV [...] Read more.

The poor water solubility of a significant number of active pharmaceutical ingredients (API) remains one of the main challenges in the drug development process, causing low bioavailability and therapeutic failure of drug candidates. Curcumin is a well-known Biopharmaceutics Classification System (BCS) class IV drug, characterized by lipophilicity and low permeability, which hampers topical bioavailability. Given these premises, the aim of this work was the design and the development of curcumin nanocrystals and their incorporation into natural inorganic hydrogels for topical application. Curcumin nanocrystals were manufactured by the wet ball milling technique and then loaded in clay-based hydrogels. Bentonite and/or palygorskite were selected as the inorganic gelling agents. Curcumin nanocrystal-loaded hydrogels were manufactured by means of a homogenization process and characterized with respect to their chemico-physical properties, in vitro release, antioxidant activity and skin permeation. The results highlighted that the presence of bentonite provided an increase of curcumin skin penetration and simultaneously allowed its radical scavenging properties, due to the desirable rheological characteristics, which should guarantee the necessary contact time of the gel with the skin. Full article

(This article belongs to the Special Issue Special Issue in Honor of Professor Carla Caramella)

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15 pages, 1507 KiB

Open AccessArticle

An Alternative Device for the Topical Treatment of Oral Cancer: Development and Ex-Vivo Evaluation of Imiquimod-Loaded Polysaccharides Formulations

by Paula de Freitas Rosa Remiro, Mariana Harue Taniguchi Nagahara, Martina Ghezzi, Alessia Filippini, Anna Demurtas, Silvia Pescina, Patrizia Santi, Cristina Padula, Ângela Maria Moraes and Sara Nicoli

Pharmaceutics 2022, 14(12), 2573; https://doi.org/10.3390/pharmaceutics14122573 - 23 Nov 2022

Cited by 1 | Viewed by 1731

Abstract

The topical use of imiquimod (IMQ), a non-specific immune response modifier, showed to be a promising therapeutic option for the early-stage treatment of some type of oral cancer, even when performed with a formulation (Aldara^®) developed and approved for skin application. [...] Read more.

The topical use of imiquimod (IMQ), a non-specific immune response modifier, showed to be a promising therapeutic option for the early-stage treatment of some type of oral cancer, even when performed with a formulation (Aldara^®) developed and approved for skin application. The aim of this work was the development of buccal formulations for the topical administration of IMQ with improved mucosal retention and reduced trans-mucosal permeation when compared to the reference formulation. Three different hydrogels based on carboxymethyl chitosan (CMChit), sodium alginate (A), and xanthan gum (X) in different combinations were prepared, and the loading of imiquimod was successfully performed by using a micellar formulation based on d-α-tocopheril polyethylene glycol 100 succinate (TPGS). Except for CMChit formulation, in all the other cases, the performance in vitro on the mucosa resulted comparable to the commercial formulation, despite the drug loading being 50-fold lower. Converting the gels in films did not modify the IMQ accumulated with respect to the correspondent gel formulation but produced as a positive effect a significant reduction in the amount permeated. Compared to the commercial formulation, this reduction was significant (p < 0.01) in the case of X film, resulting in an improvement of the retained/permeated ratio from 1 to 5.44. Mucoadhesion evaluation showed similar behavior when comparing the developed gels and the commercial formulation, and an excellent bioadhesion was observed for the films. Full article

(This article belongs to the Special Issue Special Issue in Honor of Professor Carla Caramella)

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18 pages, 4643 KiB

Open AccessArticle

Hybrid Lipid/Clay Carrier Systems Containing Annatto Oil for Topical Formulations

by Raquel de Melo Barbosa, Aliana Monteiro Leite, Fátima García-Villén, Rita Sánchez-Espejo, Pilar Cerezo, César Viseras, Angela Faccendini, Giuseppina Sandri, Fernanda Nervo Raffin and Túlio Flávio Accioly de Lima e Moura

Pharmaceutics 2022, 14(5), 1067; https://doi.org/10.3390/pharmaceutics14051067 - 17 May 2022

Viewed by 1763

Abstract

Nanocomposites formed by clay and lipid carriers (NLCs) show a high potential for providing controlled release and specific delivery of bioactive molecules and have recently gained attention in the pharmaceutical sector due to their ability to transport hydrophilic and hydrophobic drugs. Recent studies [...] Read more.

Nanocomposites formed by clay and lipid carriers (NLCs) show a high potential for providing controlled release and specific delivery of bioactive molecules and have recently gained attention in the pharmaceutical sector due to their ability to transport hydrophilic and hydrophobic drugs. Recent studies have recognized the biological activity of the oil of Bixa orellana L. (AO) with regards to its healing, antioxidant, antibacterial, and anti-leishmanial properties. Therefore, the purpose of this study is the preparation and characterization of hybrid systems based on lipid nanocarriers and laponite for the delivery of AO. NLCs were prepared by the fusion-emulsification method, using cetyl palmitate (CP) or myristyl myristate (MM), AO, and Poloxamer 188. The morphology, hydrodynamic diameters, zeta potential (ZP), polydispersity index (PDI), thermal analysis, X-ray diffraction analysis (XRD), viscosity behavior, and cytotoxicity testing of the hybrid systems were performed. The thermal study and X-ray diffraction analyses (XRD) revealed polymorphic structural changes compatible with the amorphization of the material. Rheological assays highlighted a typical pseudoplastic behavior in all systems (MM and CP with LAP). The hybrid systems’ morphology, size diameters, and PDIs were similar, preset spherical and monodisperse structures (≈200 nm; <0.3), without significant change up to sixty days. The ZP values differed from each other, becoming higher with increasing AO concentration. XEDS spectra and elemental X-ray maps show peaks of lipids (organic components, C and O) and inorganic components O, Mg, and Si. All samples showed cell viability above 60%. The results indicated a stable, biocompatible hybrid system that can be an alternative for topical application. Full article

(This article belongs to the Special Issue Special Issue in Honor of Professor Carla Caramella)

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18 pages, 3751 KiB

Open AccessArticle

Anti-Inflammatory and Analgesic Evaluation of a Phytochemical Intercalated into Layered Double Hydroxide

by Viviane A. Guilherme, Vanessa R. R. Cunha, Eneida de Paula, Daniele R. de Araujo and Vera R. L. Constantino

Pharmaceutics 2022, 14(5), 934; https://doi.org/10.3390/pharmaceutics14050934 - 25 Apr 2022

Cited by 6 | Viewed by 1971

Abstract

Coumaric acid (CouH), an antioxidant molecule assimilated by food consumption, was intercalated into layered double hydroxide (LDH) nanocarrier, having zinc and aluminium ions in the layers (LDH-Cou), to evaluate its pharmacological activity through in vitro and in vivo assays in mice. Therefore, the [...] Read more.

Coumaric acid (CouH), an antioxidant molecule assimilated by food consumption, was intercalated into layered double hydroxide (LDH) nanocarrier, having zinc and aluminium ions in the layers (LDH-Cou), to evaluate its pharmacological activity through in vitro and in vivo assays in mice. Therefore, the following tests were performed: coumarate delivery in saline solution, fibroblasts’ cell viability using neutral red, peritonitis induced by carrageenan, formalin test, acetic-acid-induced writhing, and tail-flick assay, for the non-intercalated CouH and the intercalated LDH-Cou system. Furthermore, different pharmacological pathways were also investigated to evaluate their possible anti-inflammatory and antinociceptive mechanisms of action, in comparison to traditionally used agents (morphine, naloxone, caffeine, and indomethacin). The LDH-Cou drug delivery system showed more pronounced anti-inflammatory effect than CouH but not more than that evoked by the classic non-steroidal anti-inflammatory drug (NSAID) indomethacin. For the analgesic effect, according to the tail-flick test, the treatment with LDH-Cou expressively increased the analgesia duration (p < 0.001) by approximately 1.7–1.8 times compared to CouH or indomethacin. Thus, the results pointed out that the LDH-Cou system induced in vivo analgesic and anti-inflammatory activities and possibly uses similar mechanisms to that observed for classic NSAIDs, such as indomethacin. Full article

(This article belongs to the Special Issue Special Issue in Honor of Professor Carla Caramella)

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14 pages, 3093 KiB

Open AccessArticle

Escinosomes: Safe and Successful Nanovesicles to Deliver Andrographolide by a Subcutaneous Route in a Mice Model of Oxaliplatin-Induced Neuropathy

by Giulia Vanti, Michela Capizzi, Lorenzo Di Cesare Mannelli, Elena Lucarini, Maria Camilla Bergonzi, Carla Ghelardini and Anna Rita Bilia

Pharmaceutics 2022, 14(3), 493; https://doi.org/10.3390/pharmaceutics14030493 - 24 Feb 2022

Cited by 2 | Viewed by 1670

Abstract

Andrographolide (AG) is a natural diterpene lactone endowed with considerable therapeutic potential for treating numerous diseases, including neurological disorders, but its low aqueous solubility and scarce bioavailability limit its clinical use. To overcome this problem, AG was encapsulated in escinosomes, special nanovesicles made [...] Read more.

Andrographolide (AG) is a natural diterpene lactone endowed with considerable therapeutic potential for treating numerous diseases, including neurological disorders, but its low aqueous solubility and scarce bioavailability limit its clinical use. To overcome this problem, AG was encapsulated in escinosomes, special nanovesicles made of escin (ESN), a natural saponin, and phosphatidylcholine. Escinosomes loaded with AG had an average size of 164.7 ± 13.30 nm, optimal polydispersity index (0.190 ± 0.0890) and high ζ-potential (−35.4 ± 0.451 mV), and significantly loaded the active substance—the encapsulation efficiency of AG was about 88%. Escinosomes allowed the prolonged release of AG over time, without burst effects—about 85% AG was released after 24 h. Morphological analysis by cryo-transmission electron microscopy showed nanovesicles with a spherical shape, unilamellar and oligolamellar structures, and dimensions in agreement with those measured by dynamic light scattering. In addition, stability studies were performed on AG-loaded escinosomes stored for one month at 4 °C. The pain-relieving efficacy of these nanovesicles was tested in a rat model of oxaliplatin-induced neuropathy. AG-loaded escinosomes, subcutaneously administered, effectively reduced the thermal allodynia characteristic of chemotherapy-induced neuropathy, enhancing and prolonging the effect of the natural compound. Overall, AG-loaded escinosomes were found to be excellent for loading AG, physically and chemically stable for one-month storage, and with controlled-release properties, making the formulation an ideal pharmacological approach for persistent pain treatment. Full article

(This article belongs to the Special Issue Special Issue in Honor of Professor Carla Caramella)

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19 pages, 5043 KiB

Open AccessEditor’s ChoiceArticle

Wound Dressing: Combination of Acacia Gum/PVP/Cyclic Dextrin in Bioadhesive Patches Loaded with Grape Seed Extract

by Cinzia Pagano, Francesca Luzi, Maurizio Ricci, Alessandro Di Michele, Debora Puglia, Maria Rachele Ceccarini, Tommaso Beccari, Francesca Blasi, Lina Cossignani, Aurélie Schoubben, Sara Primavilla, César Antonio Viseras Iborra and Luana Perioli

Pharmaceutics 2022, 14(3), 485; https://doi.org/10.3390/pharmaceutics14030485 - 22 Feb 2022

Cited by 14 | Viewed by 2496

Abstract

The success of wound treatment is conditioned by the combination of both suitable active ingredients and formulation. Grape seed extract (GSE), a waste by-product obtained by grape processing, is a natural source rich in many phenolic compounds responsible for antioxidant, anti-inflammatory, and antimicrobial [...] Read more.

The success of wound treatment is conditioned by the combination of both suitable active ingredients and formulation. Grape seed extract (GSE), a waste by-product obtained by grape processing, is a natural source rich in many phenolic compounds responsible for antioxidant, anti-inflammatory, and antimicrobial activities and for this reason useful to be used in a wound care product. Bioadhesive polymeric patches have been realized by combining acacia gum (AG) and polyvinylpyrrolidone (PVP). Prototypes were prepared by considering different AG/PVP ratios and the most suitable in terms of mechanical and bioadhesion properties resulted in the 9.5/1.0 ratio. This patch was loaded with GSE combined with cyclic dextrin (CD) to obtain the molecular dispersion of the active ingredient in the dried formulation. The loaded patch resulted mechanically resistant and able to release GSE by a sustained mechanism reaching concentrations able to stimulate keratinocytes’ growth, to exert both antibacterial and antioxidant activities. Full article

(This article belongs to the Special Issue Special Issue in Honor of Professor Carla Caramella)

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16 pages, 4441 KiB

Open AccessArticle

Inhalable Microparticles Embedding Calcium Phosphate Nanoparticles for Heart Targeting: The Formulation Experimental Design

by Eride Quarta, Fabio Sonvico, Ruggero Bettini, Claudio De Luca, Alessandro Dotti, Daniele Catalucci, Michele Iafisco, Lorenzo Degli Esposti, Gaia Colombo, Giovanna Trevisi, Dimitrios M. Rekkas, Alessandra Rossi, Tin Wui Wong, Francesca Buttini and Paolo Colombo

Pharmaceutics 2021, 13(11), 1825; https://doi.org/10.3390/pharmaceutics13111825 - 01 Nov 2021

Cited by 13 | Viewed by 2504

Abstract

Inhalation of Calcium Phosphate nanoparticles (CaPs) has recently unmasked the potential of this nanomedicine for a respiratory lung-to-heart drug delivery targeting the myocardial cells. In this work, we investigated the development of a novel highly respirable dry powder embedding crystalline CaPs. Mannitol was [...] Read more.

Inhalation of Calcium Phosphate nanoparticles (CaPs) has recently unmasked the potential of this nanomedicine for a respiratory lung-to-heart drug delivery targeting the myocardial cells. In this work, we investigated the development of a novel highly respirable dry powder embedding crystalline CaPs. Mannitol was selected as water soluble matrix excipient for constructing respirable dry microparticles by spray drying technique. A Quality by Design approach was applied for understanding the effect of the feed composition and spraying feed rate on typical quality attributes of inhalation powders. The in vitro aerodynamic behaviour of powders was evaluated using a medium resistance device. The inner structure and morphology of generated microparticles were also studied. The 1:4 ratio of CaPs/mannitol led to the generation of hollow microparticles, with the best aerodynamic performance. After microparticle dissolution, the released nanoparticles kept their original size. Full article

(This article belongs to the Special Issue Special Issue in Honor of Professor Carla Caramella)

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17 pages, 3205 KiB

Open AccessArticle

Chitosan Oleate Coated PLGA Nanoparticles as siRNA Drug Delivery System

by Dalila Miele, Xin Xia, Laura Catenacci, Milena Sorrenti, Silvia Rossi, Giuseppina Sandri, Franca Ferrari, John J. Rossi and Maria Cristina Bonferoni

Pharmaceutics 2021, 13(10), 1716; https://doi.org/10.3390/pharmaceutics13101716 - 17 Oct 2021

Cited by 12 | Viewed by 2542

Abstract

Oligonucleotide therapeutics such as miRNAs and siRNAs represent a class of molecules developed to modulate gene expression by interfering with ribonucleic acids (RNAs) and protein synthesis. These molecules are characterized by strong instability and easy degradation due to nuclease enzymes. To avoid these [...] Read more.

Oligonucleotide therapeutics such as miRNAs and siRNAs represent a class of molecules developed to modulate gene expression by interfering with ribonucleic acids (RNAs) and protein synthesis. These molecules are characterized by strong instability and easy degradation due to nuclease enzymes. To avoid these drawbacks and ensure efficient delivery to target cells, viral and non-viral vectors are the two main approaches currently employed. Viral vectors are one of the major vehicles in gene therapy; however, the potent immunogenicity and the insertional mutagenesis is a potential issue for the patient. Non-viral vectors, such as polymeric nanocarriers, provide a safer and more efficient delivery of RNA-interfering molecules. The aim of this work is to employ PLGA core nanoparticles shell-coated with chitosan oleate as siRNA carriers. An siRNA targeted on HIV-1, directed against the viral Tat/Rev transcripts was employed as a model. The ionic interaction between the oligonucleotide’s moieties, negatively charged, and the positive surface charges of the chitosan shell was exploited to associate siRNA and nanoparticles. Non-covalent bonds can protect siRNA from nuclease degradation and guarantee a good cell internalization and a fast release of the siRNA into the cytosolic portion, allowing its easy activation. Full article

(This article belongs to the Special Issue Special Issue in Honor of Professor Carla Caramella)

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19 pages, 4951 KiB

Open AccessArticle

Mechanochemical Synthesis and Physicochemical Characterization of Previously Unreported Praziquantel Solvates with 2-Pyrrolidone and Acetic Acid

by Debora Zanolla, Lara Gigli, Dritan Hasa, Michele R. Chierotti, Mihails Arhangelskis, Nicola Demitri, William Jones, Dario Voinovich and Beatrice Perissutti

Pharmaceutics 2021, 13(10), 1606; https://doi.org/10.3390/pharmaceutics13101606 - 02 Oct 2021

Cited by 10 | Viewed by 2036

Abstract

Two new solvates of the widely used anthelminthic Praziquantel (PZQ) were obtained through mechanochemical screening with different liquid additives. Specifically, 2-pyrrolidone and acetic acid gave solvates with 1:1 stoichiometry (PZQ-AA and PZQ-2P, respectively). A wide-ranging characterization of the new solid forms was carried [...] Read more.

Two new solvates of the widely used anthelminthic Praziquantel (PZQ) were obtained through mechanochemical screening with different liquid additives. Specifically, 2-pyrrolidone and acetic acid gave solvates with 1:1 stoichiometry (PZQ-AA and PZQ-2P, respectively). A wide-ranging characterization of the new solid forms was carried out by means of powder X-ray diffraction, differential scanning calorimetry, FT-IR, solid-state NMR and biopharmaceutical analyses (solubility and intrinsic dissolution studies). Besides, the crystal structures of the two new solvates were solved from their Synchrotron-PXRD pattern: the solvates are isostructural, with equivalent triclinic packing. In both structures acetic acid and 2-pyrrolidone showed a strong interaction with the PZQ molecule via hydrogen bond. Even though previous studies have shown that PZQ is conformationally flexible, the same syn conformation as the PZQ Form A of the C=O groups of the piperazinone-cyclohexylcarbonyl segment is involved in these two new solid forms. In terms of biopharmaceutical properties, PZQ-AA and PZQ-2P exhibited water solubility and intrinsic dissolution rate much greater than those of anhydrous Form A. Full article

(This article belongs to the Special Issue Special Issue in Honor of Professor Carla Caramella)

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14 pages, 3930 KiB

Open AccessArticle

Probing Critical Physical Properties of Lactose-Polyethylene Glycol Microparticles in Pulmonary Delivery of Chitosan Nanoparticles

by Nasser Alhajj, Idanawati Naharudin, Paolo Colombo, Eride Quarta and Tin Wui Wong

Pharmaceutics 2021, 13(10), 1581; https://doi.org/10.3390/pharmaceutics13101581 - 29 Sep 2021

Cited by 3 | Viewed by 2285

Abstract

Pulmonary delivery of chitosan nanoparticles is met with nanoparticle agglomeration and exhalation. Admixing lactose-based microparticles (surface area-weighted diameter~5 μm) with nanoparticles mutually reduces particle agglomeration through surface adsorption phenomenon. Lactose-polyethylene glycol (PEG) microparticles with different sizes, morphologies and crystallinities were prepared by a [...] Read more.

Pulmonary delivery of chitosan nanoparticles is met with nanoparticle agglomeration and exhalation. Admixing lactose-based microparticles (surface area-weighted diameter~5 μm) with nanoparticles mutually reduces particle agglomeration through surface adsorption phenomenon. Lactose-polyethylene glycol (PEG) microparticles with different sizes, morphologies and crystallinities were prepared by a spray drying method using varying PEG molecular weights and ethanol contents. The chitosan nanoparticles were similarly prepared. In vitro inhalation performance and peripheral lung deposition of chitosan nanoparticles were enhanced through co-blending with larger lactose-PEG microparticles with reduced specific surface area. These microparticles had reduced inter-microparticle interaction, thereby promoting microparticle–nanoparticle interaction and facilitating nanoparticles flow into peripheral lung. Full article

(This article belongs to the Special Issue Special Issue in Honor of Professor Carla Caramella)

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7 pages, 1959 KiB

Open AccessArticle

Design of the Prototype of Contact Drawing Device for Potential Individual Therapeutic Fiber Formation Purposes

by István Sebe, István Kovács and Romána Zelkó

Pharmaceutics 2021, 13(6), 875; https://doi.org/10.3390/pharmaceutics13060875 - 13 Jun 2021

Viewed by 1847

Abstract

Pharmaceutical compounding enables the preparation of unlicensed medicine to meet specific patient needs that do not have a licensed medicine available on the market. It must be performed in the best possible circumstance by certified pharmacists using validated standard operating procedures to obtain [...] Read more.

Pharmaceutical compounding enables the preparation of unlicensed medicine to meet specific patient needs that do not have a licensed medicine available on the market. It must be performed in the best possible circumstance by certified pharmacists using validated standard operating procedures to obtain the highest quality medicinal product. The various spinning techniques provide drug delivery systems easily adapted to individual patient’s needs among the emerging technologies. The primary purpose of the present work was to introduce the prototype of a contact drawing device for the compounding of drug delivery systems for individual in-patient needs. The preliminary experiments resulted in oriented fibers of micrometer diameter range. The device can be placed in controlled conditions and could provide drug-loaded fibrous sheets for further treatments assuring the individual patient’s medicine need of the required quality. Full article

(This article belongs to the Special Issue Special Issue in Honor of Professor Carla Caramella)

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Review

Jump to: Research

26 pages, 11932 KiB

Open AccessReview

Time-Based Formulation Strategies for Colon Drug Delivery

by Andrea Gazzaniga, Saliha Moutaharrik, Ilaria Filippin, Anastasia Foppoli, Luca Palugan, Alessandra Maroni and Matteo Cerea

Pharmaceutics 2022, 14(12), 2762; https://doi.org/10.3390/pharmaceutics14122762 - 09 Dec 2022

Cited by 10 | Viewed by 2740

Abstract

Despite poor absorption properties, delivery to the colon of bioactive compounds administered by the oral route has become a focus of pharmaceutical research over the last few decades. In particular, the high prevalence of Inflammatory Bowel Disease has driven interest because of the [...] Read more.

Despite poor absorption properties, delivery to the colon of bioactive compounds administered by the oral route has become a focus of pharmaceutical research over the last few decades. In particular, the high prevalence of Inflammatory Bowel Disease has driven interest because of the need for improved pharmacological treatments, which may provide high local drug concentrations and low systemic exposure. Colonic release has also been explored to deliver orally biologics having gut stability and permeability issues. For colon delivery, various technologies have been proposed, among which time-dependent systems rely on relatively constant small intestine transit time. Drug delivery platforms exploiting this physiological feature provide a lag time programmed to cover the entire small intestine transit and control the onset of release. Functional polymer coatings or capsule plugs are mainly used for this purpose, working through different mechanisms, such as swelling, dissolution/erosion, rupturing and/or increasing permeability, all activated by aqueous fluids. In addition, enteric coating is generally required to protect time-controlled formulations during their stay in the stomach and rule out the influence of variable gastric emptying. In this review, the rationale and main delivery technologies for oral colon delivery based on the time-dependent strategy are presented and discussed. Full article

(This article belongs to the Special Issue Special Issue in Honor of Professor Carla Caramella)

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26 pages, 5160 KiB

Open AccessEditor’s ChoiceReview

Inorganic Nanomaterials in Tissue Engineering

by Eleonora Bianchi, Barbara Vigani, César Viseras, Franca Ferrari, Silvia Rossi and Giuseppina Sandri

Pharmaceutics 2022, 14(6), 1127; https://doi.org/10.3390/pharmaceutics14061127 - 26 May 2022

Cited by 25 | Viewed by 2461

Abstract

In recent decades, the demand for replacement of damaged or broken tissues has increased; this poses the attention on problems related to low donor availability. For this reason, researchers focused their attention on the field of tissue engineering, which allows the development of [...] Read more.

In recent decades, the demand for replacement of damaged or broken tissues has increased; this poses the attention on problems related to low donor availability. For this reason, researchers focused their attention on the field of tissue engineering, which allows the development of scaffolds able to mimic the tissues’ extracellular matrix. However, tissue replacement and regeneration are complex since scaffolds need to guarantee an adequate hierarchical structured morphology as well as adequate mechanical, chemical, and physical properties to stand the stresses and enhance the new tissue formation. For this purpose, the use of inorganic materials as fillers for the scaffolds has gained great interest in tissue engineering applications, due to their wide range of physicochemical properties as well as their capability to induce biological responses. However, some issues still need to be faced to improve their efficacy. This review focuses on the description of the most effective inorganic nanomaterials (clays, nano-based nanomaterials, metal oxides, metallic nanoparticles) used in tissue engineering and their properties. Particular attention has been devoted to their combination with scaffolds in a wide range of applications. In particular, skin, orthopaedic, and neural tissue engineering have been considered. Full article

(This article belongs to the Special Issue Special Issue in Honor of Professor Carla Caramella)

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15 pages, 1748 KiB

Open AccessReview

Clays as Vehicles for Drug Photostability

by Monsuêto C. da Rocha, Thais Galdino, Pollyana Trigueiro, Luzia M. C. Honorio, Raquel de Melo Barbosa, Santiago M. Carrasco, Edson C. Silva-Filho, Josy A. Osajima and César Viseras

Pharmaceutics 2022, 14(4), 796; https://doi.org/10.3390/pharmaceutics14040796 - 05 Apr 2022

Cited by 8 | Viewed by 2206

Abstract

Clay minerals are often used due to their high adsorption capacity, which has sparked interest in their biological applications to stabilize drugs and pharmaceutical products. This research aims to summarize information about the stability of drugs, cosmetics, dermocosmetics, and pharmaceutical compounds incorporated in [...] Read more.

Clay minerals are often used due to their high adsorption capacity, which has sparked interest in their biological applications to stabilize drugs and pharmaceutical products. This research aims to summarize information about the stability of drugs, cosmetics, dermocosmetics, and pharmaceutical compounds incorporated in the structure of different clay minerals. The databases used to search the articles were Web of Science, Scopus, PubMed, and Science Direct. Photostabilization of these compounds is reviewed and its importance demonstrated. For biological applications, the increase in solubility and bioavailability of clay minerals has proven useful for them as drug carriers. While their natural abundance, low toxicity, and accessible cost have contributed to classical applications of clay minerals, a wide range of interesting new applications may be facilitated, mainly through incorporating different organic molecules. The search for new functional materials is promising to challenge research on clay minerals in biological or biotechnological approaches. Full article

(This article belongs to the Special Issue Special Issue in Honor of Professor Carla Caramella)

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21 pages, 5444 KiB

Open AccessReview

Challenges and Complications of Poly(lactic-co-glycolic acid)-Based Long-Acting Drug Product Development

by Yi Wen Lim, Wen Siang Tan, Kok Lian Ho, Abdul Razak Mariatulqabtiah, Noor Hayaty Abu Kasim, Noorsaadah Abd. Rahman, Tin Wui Wong and Chin Fei Chee

Pharmaceutics 2022, 14(3), 614; https://doi.org/10.3390/pharmaceutics14030614 - 11 Mar 2022

Cited by 25 | Viewed by 5224

Abstract

Poly(lactic-co-glycolic acid) (PLGA) is one of the preferred polymeric inactive ingredients for long-acting parenteral drug products that are constituted of complex formulations. Despite over 30 years of use, there are still many challenges faced by researchers in formulation-related aspects pertaining to [...] Read more.

Poly(lactic-co-glycolic acid) (PLGA) is one of the preferred polymeric inactive ingredients for long-acting parenteral drug products that are constituted of complex formulations. Despite over 30 years of use, there are still many challenges faced by researchers in formulation-related aspects pertaining to drug loading and release. Until now, PLGA-based complex generic drug products have not been successfully developed. The complexity in developing these generic drug products is not just due to their complex formulation, but also to the manufacturing process of the listed reference drugs that involve PLGA. The composition and product attributes of commercial PLGA formulations vary with the drugs and their intended applications. The lack of standard compendial methods for in vitro release studies hinders generic pharmaceutical companies in their efforts to develop PLGA-based complex generic drug products. In this review, we discuss the challenges faced in developing PLGA-based long-acting injectable/implantable (LAI) drug products; hurdles that are associated with drug loading and release that are dictated by the physicochemical properties of PLGA and product manufacturing processes. Approaches to overcome these challenges and hurdles are highlighted specifically with respect to drug encapsulation and release. Full article

(This article belongs to the Special Issue Special Issue in Honor of Professor Carla Caramella)

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29 pages, 2667 KiB

Open AccessReview

Drug Delivery Strategies for Curcumin and Other Natural Nrf2 Modulators of Oxidative Stress-Related Diseases

by Nina Katarina Grilc, Matej Sova and Julijana Kristl

Pharmaceutics 2021, 13(12), 2137; https://doi.org/10.3390/pharmaceutics13122137 - 12 Dec 2021

Cited by 19 | Viewed by 4294

Abstract

Oxidative stress is associated with a wide range of diseases characterised by oxidant-mediated disturbances of various signalling pathways and cellular damage. The only effective strategy for the prevention of cellular damage is to limit the production of oxidants and support their efficient removal. [...] Read more.

Oxidative stress is associated with a wide range of diseases characterised by oxidant-mediated disturbances of various signalling pathways and cellular damage. The only effective strategy for the prevention of cellular damage is to limit the production of oxidants and support their efficient removal. The implication of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway in the cellular redox status has spurred new interest in the use of its natural modulators (e.g., curcumin, resveratrol). Unfortunately, most natural Nrf2 modulators are poorly soluble and show extensive pre-systemic metabolism, low oral bioavailability, and rapid elimination, which necessitates formulation strategies to circumvent these limitations. This paper provides a brief introduction on the cellular and molecular mechanisms involved in Nrf2 modulation and an overview of commonly studied formulations for the improvement of oral bioavailability and in vivo pharmacokinetics of Nrf2 modulators. Some formulations that have also been studied in vivo are discussed, including solid dispersions, self-microemulsifying drug delivery systems, and nanotechnology approaches, such as polymeric and solid lipid nanoparticles, nanocrystals, and micelles. Lastly, brief considerations of nano drug delivery systems for the delivery of Nrf2 modulators to the brain, are provided. The literature reviewed shows that the formulations discussed can provide various improvements to the bioavailability and pharmacokinetics of natural Nrf2 modulators. This has been demonstrated in animal models and clinical studies, thereby increasing the potential for the translation of natural Nrf2 modulators into clinical practice. Full article

(This article belongs to the Special Issue Special Issue in Honor of Professor Carla Caramella)

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15 pages, 1178 KiB

Open AccessReview

Understanding the Importance of Capsules in Dry Powder Inhalers

by Francesca Buttini, Eride Quarta, Chiara Allegrini and Federico Lavorini

Pharmaceutics 2021, 13(11), 1936; https://doi.org/10.3390/pharmaceutics13111936 - 16 Nov 2021

Cited by 17 | Viewed by 9752

Abstract

Pulmonary drug delivery is currently the focus of research and development because of its potential to produce maximum therapeutic benefit to patients by directing the drug straight to the lung disease site. Among all the available delivery options, one popular, proven and convenient [...] Read more.

Pulmonary drug delivery is currently the focus of research and development because of its potential to produce maximum therapeutic benefit to patients by directing the drug straight to the lung disease site. Among all the available delivery options, one popular, proven and convenient inhaler device is the capsule-based dry powder inhaler (cDPI) for the treatment of an increasingly diverse range of diseases. cDPIs use a hard capsule that contains a powder formulation which consists of a mixture of a micronized drug and a carrier usually the lactose, known for its good lung tolerance. The capsule is either inserted into the device during manufacturer or by the patient prior to use. After perforating, opening or cut the capsule in the device, patients take a deep and rapid breath to inhale the powder, using air as the vector of drug displacement. The system is simple, relatively cheap and characterized by a lower carbon footprint than that of pressurized metered dose inhalers. This article reviews cDPI technology, focusing particularly on the importance of capsule characteristics and their function as a drug reservoir in cDPIs. Full article

(This article belongs to the Special Issue Special Issue in Honor of Professor Carla Caramella)

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46 pages, 11949 KiB

Open AccessReview

Clay Minerals as Bioink Ingredients for 3D Printing and 3D Bioprinting: Application in Tissue Engineering and Regenerative Medicine

by Fátima García-Villén, Sandra Ruiz-Alonso, Markel Lafuente-Merchan, Idoia Gallego, Myriam Sainz-Ramos, Laura Saenz-del-Burgo and Jose Luis Pedraz

Pharmaceutics 2021, 13(11), 1806; https://doi.org/10.3390/pharmaceutics13111806 - 28 Oct 2021

Cited by 21 | Viewed by 4005

Abstract

The adaptation and progress of 3D printing technology toward 3D bioprinting (specifically adapted to biomedical purposes) has opened the door to a world of new opportunities and possibilities in tissue engineering and regenerative medicine. In this regard, 3D bioprinting allows for the production [...] Read more.

The adaptation and progress of 3D printing technology toward 3D bioprinting (specifically adapted to biomedical purposes) has opened the door to a world of new opportunities and possibilities in tissue engineering and regenerative medicine. In this regard, 3D bioprinting allows for the production of tailor-made constructs and organs as well as the production of custom implants and medical devices. As it is a growing field of study, currently, the attention is heeded on the optimization and improvement of the mechanical and biological properties of the so-called bioinks/biomaterial inks. One of the strategies proposed is the use of inorganic ingredients (clays, hydroxyapatite, graphene, carbon nanotubes and other silicate nanoparticles). Clays have proven to be useful as rheological and mechanical reinforcement in a wide range of fields, from the building industry to pharmacy. Moreover, they are naturally occurring materials with recognized biocompatibility and bioactivity, revealing them as optimal candidates for this cutting-edge technology. This review deals with the use of clays (both natural and synthetic) for tissue engineering and regenerative medicine through 3D printing and bioprinting. Despite the limited number of studies, it is possible to conclude that clays play a fundamental role in the formulation and optimization of bioinks and biomaterial inks since they are able to improve their rheology and mechanical properties, thus improving printability and construct resistance. Additionally, they have also proven to be exceptionally functional ingredients (enhancing cellular proliferation, adhesion, differentiation and alignment), controlling biodegradation and carrying/releasing actives with tissue regeneration therapeutic activities. Full article

(This article belongs to the Special Issue Special Issue in Honor of Professor Carla Caramella)

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20 pages, 1682 KiB

Open AccessReview

Polymeric and Lipid Nanoparticles: Which Applications in Pediatrics?

by Noelia Nieto González, Antonella Obinu, Giovanna Rassu, Paolo Giunchedi and Elisabetta Gavini

Pharmaceutics 2021, 13(5), 670; https://doi.org/10.3390/pharmaceutics13050670 - 07 May 2021

Cited by 23 | Viewed by 3373

Abstract

This review aims to provide the state of the art on polymeric and lipid nanoparticles, used or suggested to approach pediatric diseases’ problems and needs, and to inspire new researches in this field. Several drugs are currently not available in formulations suitable for [...] Read more.

This review aims to provide the state of the art on polymeric and lipid nanoparticles, used or suggested to approach pediatric diseases’ problems and needs, and to inspire new researches in this field. Several drugs are currently not available in formulations suitable for pediatric patients. The United States Pediatric Formulation Initiative suggested applying new technologies to pediatric drug formulations, for instance, nanotechnology. The literature analysis showed that polymeric and lipid nanoparticles have been widely studied to treat pediatric diseases, and albumin nanoparticles and liposomes are already used in clinical practice. Nevertheless, these studies are focused almost exclusively on pediatric cancer treatment. Although nanomedicine may solve many needs of pediatric diseases and medicines, the unavailability of data on pharmacokinetics, safety and efficacy of both drugs and nanoparticles in pediatric patients limits the development of new pediatric medicines based on nanoparticles. Therefore, nanomedicine applied in pediatrics remains a significant challenge in the near future. Full article

(This article belongs to the Special Issue Special Issue in Honor of Professor Carla Caramella)

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