Pharmaceutics

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18 pages, 3472 KiB

Open AccessArticle

Evaluation and Comparison of Solid Lipid Nanoparticles (SLNs) and Nanostructured Lipid Carriers (NLCs) as Vectors to Develop Hydrochlorothiazide Effective and Safe Pediatric Oral Liquid Formulations

by Paola Mura, Francesca Maestrelli, Mario D’Ambrosio, Cristina Luceri and Marzia Cirri

Pharmaceutics 2021, 13(4), 437; https://doi.org/10.3390/pharmaceutics13040437 - 24 Mar 2021

Cited by 62 | Viewed by 5156

Abstract

The aim of this study was the optimization of solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) in terms of physicochemical and biopharmaceutical properties, to develop effective and stable aqueous liquid formulations of hydrochlorothiazide, suitable for paediatric therapy, overcoming its low-solubility and [...] Read more.

The aim of this study was the optimization of solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) in terms of physicochemical and biopharmaceutical properties, to develop effective and stable aqueous liquid formulations of hydrochlorothiazide, suitable for paediatric therapy, overcoming its low-solubility and poor-stability problems. Based on solubility studies, Precirol^® ATO5 and Transcutol^® HP were used as solid and liquid lipids, respectively. The effect of different surfactants, also in different combinations and at different amounts, on particle size, homogeneity and surface-charge of nanoparticles was carefully investigated. The best formulations were selected for drug loading, and evaluated also for entrapment efficiency and release behaviour. For both SLN and NLC series, the use of Gelucire^® 44/14 as surfactant rather than PluronicF68 or Tween^® 80 yielded a marked particle size reduction (95–75 nm compared to around 600–400 nm), and an improvement in entrapment efficiency and drug release rate. NLC showed a better performance than SLN, reaching about 90% entrapped drug (vs. 80%) and more than 90% drug released after 300 min (vs. about 65%). All selected formulations showed good physical stability during 6-month storage at 4 °C, but a higher loss of encapsulated drug was found for SLNs (15%) than for NLCs (<5%). Moreover, all selected formulations revealed the absence of any cytotoxic effect, as assessed by a cell-viability test on Caco-2 cells and are able to pass the intestinal epithelium as suggested by Caco-2 uptake experiments. Full article

(This article belongs to the Special Issue Nano-Micro Encapsulation of Drugs)

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17 pages, 4183 KiB

Open AccessArticle

Endogenous Antioxidant Cocktail Loaded Hydrogel for Topical Wound Healing of Burns

by José L. Soriano, Ana C. Calpena, María J. Rodríguez-Lagunas, Òscar Domènech, Nuria Bozal-de Febrer, María L. Garduño-Ramírez and Beatriz Clares

Pharmaceutics 2021, 13(1), 8; https://doi.org/10.3390/pharmaceutics13010008 - 22 Dec 2020

Cited by 10 | Viewed by 3186

Abstract

The main goal of this work is the study of the skin wound healing efficacy of an antioxidant cocktail consisting of vitamins A, D, E and the endogenous pineal hormone melatonin (MLT), with all of these loaded into a thermosensitive hydrogel delivery system. [...] Read more.

The main goal of this work is the study of the skin wound healing efficacy of an antioxidant cocktail consisting of vitamins A, D, E and the endogenous pineal hormone melatonin (MLT), with all of these loaded into a thermosensitive hydrogel delivery system. The resulting formulation was characterized by scanning electron microscopy. The antioxidant efficacy and microbiological activity against Gram positive and Gram negative strains were also assayed. The skin healing efficacy was tested using an in vivo model which included histological evaluation. Furthermore, atomic force microscopy was employed to evaluate the wound healing efficacy of rat skin burns through the determination of its elasticity at the nanoscale using force spectroscopy analysis. The resulting hydrogel exhibited sol state at low temperature and turned into a gel at 30 ± 0.2 °C. The hydrogel containing the antioxidant cocktail showed higher scavenging activity than the hydrogel containing vitamins or MLT, separately. The formulation showed optimal antimicrobial activity. It was comparable to a commercial reference. It was also evidenced that the hydrogel containing the antioxidant cocktail exhibited the strongest healing process in the skin burns of rats, similar to the assayed commercial reference containing silver sulfadiazine. Histological studies confirmed the observed results. Finally, atomic force microscopy demonstrated a similar distribution of Young’s modulus values between burned skin treated with the commercial reference and burned skin treated with hydrogel containing the antioxidant cocktail, and all these with healthy skin. The use of an antioxidant cocktail of vitamins and MLT might be a promising treatment for skin wounds for future clinical studies. Full article

(This article belongs to the Special Issue Nano-Micro Encapsulation of Drugs)

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16 pages, 1899 KiB

Open AccessArticle

Development of a Thymoquinone Polymeric Anticancer Nanomedicine through Optimization of Polymer Molecular Weight and Nanoparticle Architecture

by Suhair Sunoqrot, Malek Alfaraj, Ala’a M. Hammad, Violet Kasabri, Dana Shalabi, Ahmad A. Deeb, Lina Hasan Ibrahim, Khaldoun Shnewer and Ismail Yousef

Pharmaceutics 2020, 12(9), 811; https://doi.org/10.3390/pharmaceutics12090811 - 27 Aug 2020

Cited by 23 | Viewed by 3660

Abstract

Thymoquinone (TQ) is a water-insoluble natural compound isolated from Nigella sativa that has demonstrated promising chemotherapeutic activity. The purpose of this study was to develop a polymeric nanoscale formulation for TQ to circumvent its delivery challenges. TQ-encapsulated nanoparticles (NPs) were fabricated using methoxy [...] Read more.

Thymoquinone (TQ) is a water-insoluble natural compound isolated from Nigella sativa that has demonstrated promising chemotherapeutic activity. The purpose of this study was to develop a polymeric nanoscale formulation for TQ to circumvent its delivery challenges. TQ-encapsulated nanoparticles (NPs) were fabricated using methoxy poly(ethylene glycol)-b-poly(ε-caprolactone) (mPEG-PCL) copolymers by the nanoprecipitation technique. Formulation variables included PCL chain length and NP architecture (matrix-type nanospheres or reservoir-type nanocapsules). The formulations were characterized in terms of their particle size, polydispersity index (PDI), drug loading efficiency, and drug release. An optimized TQ NP formulation in the form of oil-filled nanocapsules (F2-NC) was obtained with a mean hydrodynamic diameter of 117 nm, PDI of 0.16, about 60% loading efficiency, and sustained in vitro drug release. The formulation was then tested in cultured human cancer cell lines to verify its antiproliferative efficacy as a potential anticancer nanomedicine. A pilot pharmacokinetic study was also carried out in healthy mice to evaluate the oral bioavailability of the optimized formulation, which revealed a significant increase in the maximum plasma concentration (C_max) and a 1.3-fold increase in bioavailability compared to free TQ. Our findings demonstrate that the versatility of polymeric NPs can be effectively applied to design a nanoscale delivery platform for TQ that can overcome its biopharmaceutical limitations. Full article

(This article belongs to the Special Issue Nano-Micro Encapsulation of Drugs)

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19 pages, 3229 KiB

Open AccessArticle

π-Donor/π-Acceptor Interactions for the Encapsulation of Neurotransmitters on Functionalized Polysilicon-Based Microparticles

by Sandra Giraldo, María E. Alea-Reyes, David Limón, Asensio González, Marta Duch, José A. Plaza, David Ramos-López, Joaquín de Lapuente, Arántzazu González-Campo and Lluïsa Pérez-García

Pharmaceutics 2020, 12(8), 724; https://doi.org/10.3390/pharmaceutics12080724 - 1 Aug 2020

Cited by 4 | Viewed by 3431

Abstract

Bipyridinium salts, commonly known as viologens, are π-acceptor molecules that strongly interact with π-donor compounds, such as porphyrins or amino acids, leading their self-assembling. These properties have promoted us to functionalize polysilicon microparticles with bipyridinium salts for the encapsulation and release of π-donor [...] Read more.

Bipyridinium salts, commonly known as viologens, are π-acceptor molecules that strongly interact with π-donor compounds, such as porphyrins or amino acids, leading their self-assembling. These properties have promoted us to functionalize polysilicon microparticles with bipyridinium salts for the encapsulation and release of π-donor compounds such as catecholamines and indolamines. In this work, the synthesis and characterization of four gemini-type amphiphilic bipyridinium salts (1·4PF₆–4·4PF₆), and their immobilization either non-covalently or covalently on polysilicon surfaces and microparticles have been achieved. More importantly, they act as hosts for the subsequent incorporation of π-donor neurotransmitters such as dopamine, serotonin, adrenaline or noradrenaline. Ultraviolet-visible absorption and fluorescence spectroscopies and high-performance liquid chromatography were used to detect the formation of the complex in solution. The immobilization of bipyridinium salts and neurotransmitter incorporation on polysilicon surfaces was corroborated by contact angle measurements. The reduction in the bipyridinium moiety and the subsequent release of the neurotransmitter was achieved using ascorbic acid, or Vitamin C, as a triggering agent. Quantification of neurotransmitter encapsulated and released from the microparticles was performed using high-performance liquid chromatography. The cytotoxicity and genotoxicity studies of the bipyridinium salt 1·4PF₆, which was selected for the non-covalent functionalization of the microparticles, demonstrated its low toxicity in the mouse fibroblast cell line (3T3/NIH), the human liver carcinoma cell line (HepG2) and the human epithelial colorectal adenocarcinoma cell line (Caco-2). Full article

(This article belongs to the Special Issue Nano-Micro Encapsulation of Drugs)

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18 pages, 10120 KiB

Open AccessArticle

Encapsulating TGF-β1 Inhibitory Peptides P17 and P144 as a Promising Strategy to Facilitate Their Dissolution and to Improve Their Functionalization

by Nemany A. N. Hanafy, Isabel Fabregat, Stefano Leporatti and Maged El Kemary

Pharmaceutics 2020, 12(5), 421; https://doi.org/10.3390/pharmaceutics12050421 - 2 May 2020

Cited by 13 | Viewed by 3538

Abstract

Transforming growth factor-beta (TGFβ1) is considered as a master regulator for many intracellular signaling pathways, including proliferation, differentiation and death, both in health and disease. It further represents an oncogenic factor in advanced tumors allowing cancer cells to be more invasive and prone [...] Read more.

Transforming growth factor-beta (TGFβ1) is considered as a master regulator for many intracellular signaling pathways, including proliferation, differentiation and death, both in health and disease. It further represents an oncogenic factor in advanced tumors allowing cancer cells to be more invasive and prone to move into the metastatic process. This finding has received great attention for discovering new therapeutic molecules against the TGFβ1 pathway. Among many TGFβ1 inhibitors, peptides (P17 and P144) were designed to block the TGFβ1 pathway. However, their therapeutic applications have limited use, due to lack of selection for their targets and their possible recognition by the immune system and further due to their potential cytotoxicity on healthy cells. Besides that, P144 is a highly hydrophobic molecule with less dissolution even in organic solution. Here, we aimed to overcome the dissolution of P144, as well as design nano-delivery strategies to protect normal cells, to increase cellular penetration and to raise the targeted therapy of both P17 and P144. Peptides were encapsulated in moieties of polymer hybrid protein. Their assembly was investigated by TEM, microplate spectrum analysis and fluorescence microscopy. SMAD phosphorylation was analyzed by Western blot as a hallmark of their biological efficiency. The results showed that the encapsulation of P17 and P144 might improve their potential therapeutic applications. Full article

(This article belongs to the Special Issue Nano-Micro Encapsulation of Drugs)

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14 pages, 10249 KiB

Open AccessArticle

Crosslinked Hyaluronan Electrospun Nanofibers for Ferulic Acid Ocular Delivery

by Maria Aurora Grimaudo, Angel Concheiro and Carmen Alvarez-Lorenzo

Pharmaceutics 2020, 12(3), 274; https://doi.org/10.3390/pharmaceutics12030274 - 17 Mar 2020

Cited by 46 | Viewed by 4007

Abstract

Electrospun nanofibers are gaining interest as ocular drug delivery platforms that may adapt to the eye surface and provide sustained release. The aim of this work was to design an innovative ophthalmic insert composed of hyaluronan (HA) nanofibers for the dual delivery of [...] Read more.

Electrospun nanofibers are gaining interest as ocular drug delivery platforms that may adapt to the eye surface and provide sustained release. The aim of this work was to design an innovative ophthalmic insert composed of hyaluronan (HA) nanofibers for the dual delivery of an antioxidant (ferulic acid, FA) and an antimicrobial peptide (ε-polylysine, ε-PL). Polyvinylpyrrolidone (PVP) was added to facilitate the electrospinning process. Fibers with diameters of approx. 100 nm were obtained with PVP 5%-HA 0.8% w/v and PVP 10%-HA 0.5% w/v mixtures in ethanol:water 4:6 v/v. An increase in PVP concentration to 20% w/v in both presence and absence of HA rendered fibers of approx. 1 µm. PVP 5%-HA 0.8% w/v fibers were loaded with 83.3 ± 14.0 µg FA per mg. After nanofibers crosslinking with ε-PL, blank and FA-loaded inserts showed a mean thickness of 270 ± 21 µm and 273 ± 41 µm, respectively. Blank and FA-loaded inserts completely released ε-PL within 30 min under sink conditions, whereas FA-loaded inserts released the antioxidant within 20 min. Both blank and FA-loaded inserts were challenged against Pseudomonas aeruginosa and Staphylococcus aureus, demonstrating their efficacy against relevant microbial species. Full article

(This article belongs to the Special Issue Nano-Micro Encapsulation of Drugs)

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13 pages, 1277 KiB

Open AccessArticle

Perillaldehyde 1,2-epoxide Loaded SLN-Tailored mAb: Production, Physicochemical Characterization and In Vitro Cytotoxicity Profile in MCF-7 Cell Lines

by Eliana B. Souto, Selma B. Souto, Aleksandra Zielinska, Alessandra Durazzo, Massimo Lucarini, Antonello Santini, Olaf K. Horbańczuk, Atanas G. Atanasov, Conrado Marques, Luciana N. Andrade, Amélia M. Silva and Patricia Severino

Pharmaceutics 2020, 12(2), 161; https://doi.org/10.3390/pharmaceutics12020161 - 16 Feb 2020

Cited by 41 | Viewed by 3931

Abstract

We have developed a new cationic solid lipid nanoparticle (SLN) formulation, composed of Compritol ATO 888, poloxamer 188 and cetyltrimethylammonium bromide (CTAB), to load perillaldehyde 1,2-epoxide, and surface-tailored with a monoclonal antibody for site-specific targeting of human epithelial growth receptor 2 (HER2). Perillaldehyde [...] Read more.

We have developed a new cationic solid lipid nanoparticle (SLN) formulation, composed of Compritol ATO 888, poloxamer 188 and cetyltrimethylammonium bromide (CTAB), to load perillaldehyde 1,2-epoxide, and surface-tailored with a monoclonal antibody for site-specific targeting of human epithelial growth receptor 2 (HER2). Perillaldehyde 1,2-epoxide-loaded cationic SLN (cPa-SLN), with a mean particle size (z-Ave) of 275.31 ± 4.78 nm and polydispersity index (PI) of 0.303 ± 0.081, were produced by high shear homogenization. An encapsulation efficiency of cPa-SLN above 80% was achieved. The release of perillaldehyde 1,2-epoxide from cationic SLN followed the Korsemeyer–Peppas kinetic model, which is typically seen in nanoparticle formulations. The lipid peroxidation of cPa-SLN was assessed by the capacity to produce thiobarbituric acid-reactive substances, while the antioxidant activity was determined by the capacity to scavenge the stable radical DPPH. The surface functionalization of cPa-SLN with the antibody was done via streptavidin-biotin interaction, monitoring z-Ave, PI and ZP of the obtained assembly (cPa-SLN-S_Ab), as well as its stability in phosphate buffer. The effect of plain cationic SLN (c-SLN, monoterpene free), cPa-SLN and cPa-SLN-S_Ab onto the MCF-7 cell lines was evaluated in a concentration range from 0.01 to 0.1 mg/mL, confirming that streptavidin adsorption onto cPa-SLN-S_Ab improved the cell viability in comparison to the cationic cPa-SLN. Full article

(This article belongs to the Special Issue Nano-Micro Encapsulation of Drugs)

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14 pages, 1853 KiB

Open AccessArticle

Epidermal Delivery of Retinyl Palmitate Loaded Transfersomes: Penetration and Biodistribution Studies

by Eloy Pena-Rodríguez, Mari Carmen Moreno, Bárbara Blanco-Fernandez, Jordi González and Francisco Fernández-Campos

Pharmaceutics 2020, 12(2), 112; https://doi.org/10.3390/pharmaceutics12020112 - 30 Jan 2020

Cited by 29 | Viewed by 5477

Abstract

The alteration of retinoids levels in the skin can cause different disorders in the maturation of epithelial skin cells. Topical administration of these lipophilic molecules is a challenge that can be addressed by encapsulation into drug delivery systems. In this study, retinyl palmitate [...] Read more.

The alteration of retinoids levels in the skin can cause different disorders in the maturation of epithelial skin cells. Topical administration of these lipophilic molecules is a challenge that can be addressed by encapsulation into drug delivery systems. In this study, retinyl palmitate transferosomes formulated in cream were developed and the increases in the penetration of the active ingredients as well as the biodistribution were evaluated in vitro and in vivo. Transfersomes demonstrated a significant increase in the administration of retinyl palmitate to the epidermis by quantification of the active ingredients in the different layers of the skin, as well as by fluorescence microscopy of biopsies of non-dermatomized pig-ear skin. These results suggest that transfersomes may be an efficient vehicle for the delivery of retinoids to inner layers of the skin, such as the epidermis. Full article

(This article belongs to the Special Issue Nano-Micro Encapsulation of Drugs)

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