Research

13 pages, 2476 KiB

Open AccessArticle

Chitosan/poly(lactic-co-glycolic)acid Nanoparticle Formulations with Finely-Tuned Size Distributions for Enhanced Mucoadhesion

by Feipeng Yang, Maleen Cabe, Hope A. Nowak and Kelly A. Langert

Pharmaceutics 2022, 14(1), 95; https://doi.org/10.3390/pharmaceutics14010095 - 01 Jan 2022

Cited by 9 | Viewed by 2252

Abstract

Non-parenteral drug delivery systems using biomaterials have advantages over traditional parenteral strategies. For ocular and intranasal delivery, nanoparticulate systems must bind to and permeate through mucosal epithelium and other biological barriers. The incorporation of mucoadhesive and permeation-enhancing biomaterials such as chitosan facilitate this, [...] Read more.

Non-parenteral drug delivery systems using biomaterials have advantages over traditional parenteral strategies. For ocular and intranasal delivery, nanoparticulate systems must bind to and permeate through mucosal epithelium and other biological barriers. The incorporation of mucoadhesive and permeation-enhancing biomaterials such as chitosan facilitate this, but tend to increase the size and polydispersity of the nanoparticles, making practical optimization and implementation of mucoadhesive nanoparticle formulations a challenge. In this study, we adjusted key poly(lactic-co-glycolic) acid (PLGA) nanoparticle formulation parameters including the organic solvent and co-solvent, the concentration of polymer in the organic phase, the composition of the aqueous phase, the sonication amplitude, and the inclusion of chitosan in the aqueous phase. By doing so, we prepared four statistically unique size groups of PLGA NPs and equally-sized chitosan-PLGA NP counterparts. We loaded simvastatin, a candidate for novel ocular and intranasal delivery systems, into the nanoparticles to investigate the effects of size and surface modification on drug loading and release, and we quantified size- and surface-dependent changes in mucoadhesion in vitro. These methods and findings will contribute to the advancement of mucoadhesive nanoformulations for ocular and nose-to-brain drug delivery. Full article

(This article belongs to the Special Issue Chitosan Nanoparticles in Drug Delivery)

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20 pages, 4102 KiB

Open AccessArticle

In Vitro Performance of Dutasteride-Nanostructured Lipid Carriers Coated with Lauric Acid-Chitosan Oligomer for Dermal Delivery

by Norhayati Mohamed Noor, Azila Abdul-Aziz, Khalid Sheikh, Satyanarayana Somavarapu and Kevin M. G. Taylor

Pharmaceutics 2020, 12(10), 994; https://doi.org/10.3390/pharmaceutics12100994 - 20 Oct 2020

Cited by 9 | Viewed by 4044

Abstract

Dutasteride, licensed as an oral medicine for the treatment of benign prostatic hypoplasia, has been investigated as a treatment for androgenic alopecia. In this study, the potential for dustasteride to be delivered topically in order to reduce systemic exposure, irritation of the skin, [...] Read more.

Dutasteride, licensed as an oral medicine for the treatment of benign prostatic hypoplasia, has been investigated as a treatment for androgenic alopecia. In this study, the potential for dustasteride to be delivered topically in order to reduce systemic exposure, irritation of the skin, and also cytotoxicity was explored. Chitosan oligomer (CSO) was successfully synthesised with lauric acid as a coating for a dutasteride-loaded nanostructured lipid carriers (DST-NLCs) system. DST-NLCs were prepared using a combination of melt-dispersion and ultrasonication. These negatively charged NLCs (−18.0 mV) had a mean particle size of ~184 nm, which was not significantly increased (p > 0.05) when coated with lauric acid-chitosan oligomer (CSO-LA), whilst the surface charge changed to positive (+24.8 mV). The entrapment efficiency of DST-NLCs was 97%, and coated and uncoated preparations were physically stable for up to 180 days at 4–8 °C. The drug release was slower from DST-NLCs coated with CSO-LA than from uncoated NLCs, with no detectable drug permeation through full-thickness pig ear skin from either preparation. Considering the cytotoxicity, the IC₅₀ values for the DST-NLCs, coated and uncoated with CSO-LA were greater than for dutasteride alone (p < 0.05). DST-NLCs and empty NLCs coated with CSO-LA at 25 µM increased the cell proliferation compared to the control, and no skin irritation was observed when the DST-NLC formulations were tested using EpiDerm™. The cell and skin uptake studies of coated and uncoated NLCs incorporating the fluorescent marker Coumarin-6 showed the time-dependent uptake of Coumarin-6. Overall, the findings suggest that DST-NLCs coated with CSO-LA represent a promising formulation strategy for dutasteride delivery for the treatment of androgenic alopecia, with a reduced cytotoxicity compared to that of the drug alone and lower irritancy than an ethanolic solution of dutasteride. Full article

(This article belongs to the Special Issue Chitosan Nanoparticles in Drug Delivery)

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22 pages, 6823 KiB

Open AccessArticle

Development of Metronidazole Loaded Chitosan Nanoparticles Using QbD Approach—A Novel and Potential Antibacterial Formulation

by Nagaraja Sreeharsha, Kuldeep Rajpoot, Muktika Tekade, Dnyaneshwar Kalyane, Anroop B. Nair, Katharigatta N. Venugopala and Rakesh K. Tekade

Pharmaceutics 2020, 12(10), 920; https://doi.org/10.3390/pharmaceutics12100920 - 25 Sep 2020

Cited by 52 | Viewed by 3909

Abstract

The aim of this study was to design, optimize, and develop metronidazole (Met) loaded nanoparticles (MetNp) by employing quality-based design (QbD) as well as a risk assessment methodology. A fractional factorial design was used by selecting five independent variables viz., chitosan concentration, tripolyphosphate [...] Read more.

The aim of this study was to design, optimize, and develop metronidazole (Met) loaded nanoparticles (MetNp) by employing quality-based design (QbD) as well as a risk assessment methodology. A fractional factorial design was used by selecting five independent variables viz., chitosan concentration, tripolyphosphate concentration, and acetic acid concentration as material attributes, stirring speed, and stirring time as process parameters, whereby their influence on two dependent variables such as particle size (PS) and %entrapment efficiency (%EE) was studied. MetNp were synthesized by employing an ionic-gelation technique and optimized formula obtained from the QbD design study. PS and %EE studies revealed the formation of MetNp with 558.06 ± 2.52 nm and 59.07 ± 2.15%, respectively. Furthermore, a Met release study in various simulated gastro-intestinal media suggested pH-triggered (pH > 7.0) and sustained release profile of Met from Eudragit S100 enteric-coated MetNp capsule (MetNp cap). Moreover, the stability investigation of formulations confirmed good stability with respect to their PS and residual drug content (RDC) at different temperature conditions. In conclusion, the QbD method was effectively utilized in the development of MetNp and enteric-coated MetNp cap depicting their potential to release Met through MetNp cap only in the colon region and can be utilized for the treatment of amoebiasis in the colon. Full article

(This article belongs to the Special Issue Chitosan Nanoparticles in Drug Delivery)

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21 pages, 4508 KiB

Open AccessArticle

Characterization and Mathematical Modeling of Alginate/Chitosan-Based Nanoparticles Releasing the Chemokine CXCL12 to Attract Glioblastoma Cells

by Suzanne Gascon, Angéla Giraldo Solano, Wiam El Kheir, Hélène Therriault, Pierre Berthelin, Bettina Cattier, Bernard Marcos, Nick Virgilio, Benoit Paquette, Nathalie Faucheux and Marc-Antoine Lauzon

Pharmaceutics 2020, 12(4), 356; https://doi.org/10.3390/pharmaceutics12040356 - 14 Apr 2020

Cited by 11 | Viewed by 4085

Abstract

Chitosan (Chit) currently used to prepare nanoparticles (NPs) for brain application can be complexed with negatively charged polymers such as alginate (Alg) to better entrap positively charged molecules such as CXCL12. A sustained CXCL12 gradient created by a delivery system can be used, [...] Read more.

Chitosan (Chit) currently used to prepare nanoparticles (NPs) for brain application can be complexed with negatively charged polymers such as alginate (Alg) to better entrap positively charged molecules such as CXCL12. A sustained CXCL12 gradient created by a delivery system can be used, as a therapeutic approach, to control the migration of cancerous cells infiltrated in peri-tumoral tissues similar to those of glioblastoma multiforme (GBM). For this purpose, we prepared Alg/Chit NPs entrapping CXCL12 and characterized them. We demonstrated that Alg/Chit NPs, with an average size of ~250 nm, entrapped CXCL12 with ~98% efficiency for initial mass loadings varying from 0.372 to 1.490 µg/mg NPs. The release kinetic profiles of CXCL12 were dependent on the initial mass loading, and the released chemokine from NPs after seven days reached 12.6%, 32.3%, and 59.9% of cumulative release for initial contents of 0.372, 0.744, and 1.490 µg CXCL12/mg NPs, respectively. Mathematical modeling of released kinetics showed a predominant diffusive process with strong interactions between Alg and CXCL12. The CXCL12-NPs were not toxic and did not promote F98 GBM cell proliferation, while the released CXCL12 kept its chemotaxis effect. Thus, we developed an efficient and tunable CXCL12 delivery system as a promising therapeutic strategy that aims to be injected into a hydrogel used to fill the cavity after surgical tumor resection. This system will be used to attract infiltrated GBM cells prior to their elimination by conventional treatment without affecting a large zone of healthy brain tissue. Full article

(This article belongs to the Special Issue Chitosan Nanoparticles in Drug Delivery)

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21 pages, 6199 KiB

Open AccessArticle

Optimization of Thiolated Chitosan Nanoparticles for the Enhancement of in Vivo Hypoglycemic Efficacy of Sitagliptin in Streptozotocin-Induced Diabetic Rats

by Kousalya Prabahar, Ubaidulla Udhumansha and Mona Qushawy

Pharmaceutics 2020, 12(4), 300; https://doi.org/10.3390/pharmaceutics12040300 - 26 Mar 2020

Cited by 25 | Viewed by 2952

Abstract

Sitagliptin (SGN) is an antidiabetic drug used for treatment of diabetes mellitus type II. The objectives of this study were to formulate SGN in form of thiolated chitosan (TC) nanoparticles to enhance the mucoadhesion properties of SGN to the gastrointestinal tract, prolong drug [...] Read more.

Sitagliptin (SGN) is an antidiabetic drug used for treatment of diabetes mellitus type II. The objectives of this study were to formulate SGN in form of thiolated chitosan (TC) nanoparticles to enhance the mucoadhesion properties of SGN to the gastrointestinal tract, prolong drug release, decrease side effects, and enhance patient compliance. Seventeen batches of SGN-TC nanoparticles were designed by Box-Behnken design and prepared using the ionic gelation method using tripolyphosphate (TPP) as crosslinking agent. The prepared formulations were evaluated for particle size, entrapment efficiency %, and in vitro drug release. Based on the results of optimization, three formulations (F1–F3) were prepared with different drug polymer ratios (1:1, 1:2, and 1:3). The mucoadhesion study and in vivo hypoglycemic activity of three formulations were evaluated in comparison to free SGN in streptozotocin (STZ)-induced diabetic rats. The seventeen SGN-TC nanoparticles showed small particle sizes, high entrapment efficiency, and prolonged drug release. The concentration of TC polymers had highest effect on these responses. The percentage of SGN–TC nanoparticles adhered to tissue was increased and the release was prolonged as the concentration of TC polymer increased (F3 > F2 > F1). The hypoglycemic effect of SGN-TC nanoparticles was significantly higher than resulted by free SGN. It was concluded that TC nanoparticles had the ability to enhance the mucoadhesion properties of SGN and prolong the drug release. SGN-TC nanoparticles significantly reduced plasma glucose levels compared to free SGN in STZ-induced diabetic rats. Full article

(This article belongs to the Special Issue Chitosan Nanoparticles in Drug Delivery)

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18 pages, 3728 KiB

Open AccessArticle

Fabrication of Ion-Crosslinking Aminochitosan Nanoparticles for Encapsulation and Slow Release of Curcumin

by Xiaoxiao Sun, Dongyan Yu, Zhuoyang Ying, Chuqiao Pan, Nan Wang, Fangfang Huang, Junhong Ling and Xiao-kun Ouyang

Pharmaceutics 2019, 11(11), 584; https://doi.org/10.3390/pharmaceutics11110584 - 07 Nov 2019

Cited by 28 | Viewed by 3343

Abstract

Curcumin (Cur) has anticancer activities but has poor stability, which can be improved using carrier materials. In this study, chitosan was aminated to increase the number of amino groups on its surface, modified with folic acid (FA), and then made into nanoparticles by [...] Read more.

Curcumin (Cur) has anticancer activities but has poor stability, which can be improved using carrier materials. In this study, chitosan was aminated to increase the number of amino groups on its surface, modified with folic acid (FA), and then made into nanoparticles by ionic crosslinking. Owing to ion interaction, the negatively charged, non-toxic tripolyphosphate (TPP) interacted with the positively charged amino group on the aminated chitosan (AmCS) surface, producing FA-AmCS-TPP nanoparticles, which were then characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier transform infrared spectrophotometry (FT-IR), and thermogravimetric analysis (TGA). Their small particle size (175.2 ± 0.99 nm) and good surface positive potential (+42.4 mV) are beneficial for carrying antitumor drugs. We subsequently investigated whether coating of Cur by AmCS allows slow drug release by FA-AmCS-TPP nanoparticles in different pH environments, and estimated the Cur loading efficiency (EE-Cur). Our results showed that the cumulative release rate of Cur at 48 h was 56.2%, and that the EE-Cur reached 94.26 ± 0.91% with nanoparticles composed of 0.10 g AmCS, 10.0 mg FA, 10.0 mg TPP, and 15.0 mg Cur. Additionally, cytotoxicity experiments showed that the Cur/FA-AmCS-TPP nanoparticles had good targeting ability for tumor cells. Therefore, the non-toxic targeted composite nanoparticles had potential as a new antitumor agent that can overcome the limitations of Cur. Full article

(This article belongs to the Special Issue Chitosan Nanoparticles in Drug Delivery)

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Review

Jump to: Research, Other

27 pages, 15443 KiB

Open AccessReview

Chitosan Nanoparticles at the Biological Interface: Implications for Drug Delivery

by Noorjahan Aibani, Raj Rai, Parth Patel, Grace Cuddihy and Ellen K. Wasan

Pharmaceutics 2021, 13(10), 1686; https://doi.org/10.3390/pharmaceutics13101686 - 14 Oct 2021

Cited by 90 | Viewed by 6114

Abstract

The unique properties of chitosan make it a useful choice for various nanoparticulate drug delivery applications. Although chitosan is biocompatible and enables cellular uptake, its interactions at cellular and systemic levels need to be studied in more depth. This review focuses on the [...] Read more.

The unique properties of chitosan make it a useful choice for various nanoparticulate drug delivery applications. Although chitosan is biocompatible and enables cellular uptake, its interactions at cellular and systemic levels need to be studied in more depth. This review focuses on the various physical and chemical properties of chitosan that affect its performance in biological systems. We aim to analyze recent research studying interactions of chitosan nanoparticles (NPs) upon their cellular uptake and their journey through the various compartments of the cell. The positive charge of chitosan enables it to efficiently attach to cells, increasing the probability of cellular uptake. Chitosan NPs are taken up by cells via different pathways and escape endosomal degradation due to the proton sponge effect. Furthermore, we have reviewed the interaction of chitosan NPs upon in vivo administration. Chitosan NPs are immediately surrounded by a serum protein corona in systemic circulation upon intravenous administration, and their biodistribution is mainly to the liver and spleen indicating RES uptake. However, the evasion of RES system as well as the targeting ability and bioavailability of chitosan NPs can be improved by utilizing specific routes of administration and covalent modifications of surface properties. Ongoing clinical trials of chitosan formulations for therapeutic applications are paving the way for the introduction of chitosan into the pharmaceutical market and for their toxicological evaluation. Chitosan provides specific biophysical properties for effective and tunable cellular uptake and systemic delivery for a wide range of applications. Full article

(This article belongs to the Special Issue Chitosan Nanoparticles in Drug Delivery)

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68 pages, 2844 KiB

Open AccessReview

Nanosystems for the Encapsulation of Natural Products: The Case of Chitosan Biopolymer as a Matrix

by Anastasia Detsi, Eleni Kavetsou, Ioanna Kostopoulou, Ioanna Pitterou, Antonella Rozaria Nefeli Pontillo, Andromachi Tzani, Paris Christodoulou, Aristeia Siliachli and Panagiotis Zoumpoulakis

Pharmaceutics 2020, 12(7), 669; https://doi.org/10.3390/pharmaceutics12070669 - 16 Jul 2020

Cited by 95 | Viewed by 7082

Abstract

Chitosan is a cationic natural polysaccharide, which has emerged as an increasingly interesting biomaterialover the past few years. It constitutes a novel perspective in drug delivery systems and nanocarriers’ formulations due to its beneficial properties, including biocompatibility, biodegradability and low toxicity. The potentiality [...] Read more.

Chitosan is a cationic natural polysaccharide, which has emerged as an increasingly interesting biomaterialover the past few years. It constitutes a novel perspective in drug delivery systems and nanocarriers’ formulations due to its beneficial properties, including biocompatibility, biodegradability and low toxicity. The potentiality of chemical or enzymatic modifications of the biopolymer, as well as its complementary use with other polymers, further attract the scientific community, offering improved and combined properties in the final materials. As a result, chitosan has been extensively used as a matrix for the encapsulation of several valuable compounds. In this review article, the advantageous character of chitosan as a matrix for nanosystemsis presented, focusing on the encapsulation of natural products. A five-year literature review is attempted covering the use of chitosan and modified chitosan as matrices and coatings for the encapsulation of natural extracts, essential oils or pure naturally occurring bioactive compounds are discussed. Full article

(This article belongs to the Special Issue Chitosan Nanoparticles in Drug Delivery)

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Other

Jump to: Research, Review

2 pages, 195 KiB

Open AccessErratum

Erratum: Gascon S.; et al. Characterization and Mathematical Modeling of Alginate/Chitosan-Based Nanoparticles Releasing the Chemokine CXCL12 to Attract Glioblastoma Cells. Pharmaceutics 2020, 12, 356

by Suzanne Gascon, Angéla Giraldo Solano, Wiam El Kheir, Hélène Therriault, Pierre Berthelin, Bettina Cattier, Bernard Marcos, Nick Virgilio, Benoit Paquette, Nathalie Faucheux and Marc-Antoine Lauzon

Pharmaceutics 2020, 12(12), 1153; https://doi.org/10.3390/pharmaceutics12121153 - 27 Nov 2020

Cited by 1 | Viewed by 1373

Abstract

The authors wish to make the following correction to this paper [...] Full article

(This article belongs to the Special Issue Chitosan Nanoparticles in Drug Delivery)

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