Mucoadhesive Particles: A Novel, Prolonged-Release Nanocarrier of Sitagliptin for the Treatment of Diabetics

Sitagliptin (MK–0431) is a widely and commonly used oral hypoglycemic drug in the treatment of type 2 diabetes mellitus; patients typically take higher doses of this drug (50 mg, twice daily). One drawback is that only 38% of the drug is bound reversibly to plasma proteins and 79% is excreted in urine without being metabolized. To overcome this issue, there is a need for a better drug-delivery method to improve its efficacy in patients. It has been found that in existing formulations, the drug content is 72.5% ± 5% and the percentage yield is 84.9% ± 3%. In this study, sitagliptin nanoparticles (sizes ranging from 210 to 618 nm) were developed. The bioadhesion properties of the nanoparticles, as well as the swelling of the nanoparticles on the mucus membrane aided in sustained drug release. The pattern of drug release was in accordance with the Peppas model. Fourier-transform infrared (FTIR) spectroscopy demonstrated that there were no significant interactions between sitagliptin and chitosan. Differential scanning calorimetry (DSC) results showed an absence of drug peaks due to the fact that the drug was present in an amorphous state. Mucoadhesive nanoparticles were formulated using sitagliptin and were effective for about 12 hours in the gastrointestinal tract. When compared to conventional sitagliptin administration, use of a nanoparticle delivery system demonstrated greater benefits for use in oral delivery applications. This is the first time that a drug-delivery method based on the mucoadhesive properties of nanoparticles could prolong the drug-release time of sitagliptin.

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Colon-Targeted Drug Delivery Microparticles Prepared Using Electrohydrodynamic Atomization

Applied Mechanics and Materials ◽

10.4028/www.scientific.net/amm.130-134.1663 ◽

2011 ◽

Vol 130-134 ◽

pp. 1663-1667

Author(s):

Deng Guang Yu ◽

Xia Wang ◽

Ping Lu ◽

Xiao Chen ◽

Hui Peng Zhao ◽

...

Keyword(s):

Drug Delivery ◽

Targeted Drug Delivery ◽

Amorphous State ◽

In Vitro Dissolution ◽

Infrared Analysis ◽

Drug Release Profile ◽

Sustained Drug Release ◽

Scanning Calorimetry ◽

Electrohydrodynamic Atomization ◽

Targeted Drug

Electrohydrodynamic atomization (EHDA) process was exploited to prepare drug-loaded microparticles for colon-targeted drug delivery. Field emission scanning electron microscope results showed that the particles had a size of 1.3±0.7 μm. Differential scanning calorimetry (DSC) analyses and wide-angle X-ray diffraction analyses (XRD) results similarly demonstrated that the drug DS had been totally converted into an amorphous state in the EHDA microparticles with Eudragit® L-100 as the polymer matrix. Attenuated total reflectance Fourier transform infrared analysis disclosed that the secondary interactions presented between DS and Eudragit® L100 molecules. In vitro dissolution tests verified that the microparticles had a pH-dependent and sustained drug release profile. The present study provides an easy way for developing colon-targeted drug delivery microparticles.

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Synthesis of a PVA drug delivery system for controlled release of a Tramadol–Dexketoprofen combination

Journal of Materials Science Materials in Medicine ◽

10.1007/s10856-021-06529-3 ◽

2021 ◽

Vol 32 (5) ◽

Author(s):

Juan Carlos Flores-Arriaga ◽

Daniel Chavarría-Bolaños ◽

Amaury de Jesús Pozos-Guillén ◽

Vladimir Alonso Escobar-Barrios ◽

Bernardino Isaac Cerda-Cristerna

Keyword(s):

Drug Delivery ◽

Molecular Weight ◽

Citric Acid ◽

Postoperative Pain ◽

Drug Release ◽

Release Rate ◽

Poly Vinyl Alcohol ◽

Prolonged Release ◽

Scanning Calorimetry ◽

Drug Release Rate

AbstractThe local administration of analgesic combinations by means of degradable polymeric drug delivery systems is an alternative for the management of postoperative pain. We formulated a Tramadol–Dexketoprofen combination (TDC) loaded in poly(vinyl alcohol) (PVA) film. Films were prepared by the solvent casting method using three different molecular weights of PVA and crosslinking those films with citric acid, with the objective of controlling the drug release rate, which was evaluated by UV–vis spectrometry. Non-crosslinked PVA films were also evaluated in the experiments. Differential scanning calorimetry (DSC) analysis of samples corroborated the crosslinking of PVA by the citric acid. Blank and loaded PVA films were tested in vitro for its impact on blood coagulation prothrombin time (PT) and partial thromboplastin time (PTT). The swelling capacity was also evaluated. Crosslinked PVA films of higher-molecular weight showed a prolonged release rate compared with that of the lower-molecular-weight films tested. Non-crosslinked PVA films released 11–14% of TDC. Crosslinked PVA films released 80% of the TDC loaded (p < 0.05). This suggests that crosslinking films can modify the drug release rate. The blank and loaded PVA films induced PT and PTT in the normal range. The results showed that the polymeric films evaluated here have the appropriate properties to allow films to be placed directly on surgical wounds and have the capacity for controlled drug release to promote local analgesia for the control of postoperative pain.

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Coaxial Electrospinning with Mixed Solvents: From Flat to Round Eudragit L100 Nanofibers for Better Colon-Targeted Sustained Drug Release Profiles

Journal of Nanomaterials ◽

10.1155/2014/967295 ◽

2014 ◽

Vol 2014 ◽

pp. 1-8 ◽

Cited By ~ 10

Author(s):

Deng-Guang Yu ◽

Ying Xu ◽

Zan Li ◽

Lin-Ping Du ◽

Ben-Guo Zhao ◽

...

Keyword(s):

Drug Release ◽

Diclofenac Sodium ◽

Mixed Solvents ◽

Amorphous State ◽

Electrospinning Process ◽

Release Time ◽

Coaxial Electrospinning ◽

Sustained Drug Release ◽

Eudragit L100 ◽

Physical Form

A modified coaxial electrospinning process was developed for creating drug-loaded composite nanofibers. Using a mixed solvent of ethanol and N,N-dimethylacetamide as a sheath fluid, the electrospinning of a codissolving solution of diclofenac sodium (DS) and Eudragit L100 (EL100) could run smoothly and continuously without any clogging. A series of analyses were undertaken to characterize the resultant nanofibers from both the modified coaxial process and a one-fluid electrospinning in terms of their morphology, physical form of the components, and their functional performance. Compared with those from the one-fluid electrospinning, the DS-loaded EL100 fibers from the modified coaxial process were rounder and smoother and possessed higher quality in terms of diameter and distribution with the DS existing in the EL100 matrix in an amorphous state; they also provided a better colon-targeted sustained drug release profile with a longer release time period. The modified coaxial process not only can smooth the electrospinning process to prevent clogging of spinneret, but also is a useful tool to tailor the shape of electrospun nanofibers and thus endow them improved functions.

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Mucoadhesive Formulation Designs for Oral Controlled Drug Release at the Colon

Current Pharmaceutical Design ◽

10.2174/1381612826666200917143816 ◽

2020 ◽

Vol 26 ◽

Author(s):

Phuong H.L. Tran ◽

Thao T.D. Tran

Keyword(s):

Drug Delivery ◽

Controlled Release ◽

Drug Release ◽

Basic Principle ◽

Oral Delivery ◽

Drug Delivery Systems ◽

Controlled Drug Release ◽

Delivery Systems ◽

Sustained Drug Release ◽

Mucosal Tissues

: Mucoadhesive formulations have been demonstrated to result in efficient drug delivery systems with advantages over existing systems such as increased local retention and sustained drug release via adhesiveness to mucosal tissues. The controlled release of colon-targeted, orally administered drugs has recently attracted a number of studies investigating mucoadhesive systems. Consequently, substantial designs, from mucoadhesive cores to shells of particles, have been studied with promising applications. This review will provide an overview of and discuss specific strategies for developing mucoadhesive systems for colon-targeted oral delivery with controlled drug release, including mucoadhesive matrices, cross-linked mucoadhesive microparticles, coatings and mucoadhesive nanoparticles. The understanding of the basic principle of these designs and advanced formulations throughout will lead to the development of products with efficient drug delivery at the colon for therapies for different diseases.

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Targeted Delivery of Paclitaxel in Liver Cancer Using Hyaluronic Acid Functionalized Mesoporous Hollow Alumina Nanoparticles

BioMed Research International ◽

10.1155/2019/2928507 ◽

2019 ◽

Vol 2019 ◽

pp. 1-10 ◽

Cited By ~ 1

Author(s):

Yu Gao ◽

Lili Hu ◽

Ying Liu ◽

Xiaoyan Xu ◽

Chao Wu

Keyword(s):

Hyaluronic Acid ◽

Cancer Therapy ◽

Liver Cancer ◽

Drug Release ◽

Targeted Delivery ◽

Amorphous State ◽

Alumina Nanoparticles ◽

Sustained Drug Release ◽

Scanning Calorimetry ◽

Adsorption Method

Hyaluronic acid functionalized mesoporous hollow alumina nanoparticles (HMHA) were used as a tumor-targeted delivery carrier for liver cancer therapy. Paclitaxel (PAC) incorporated in the carrier by the adsorption method was analyzed by X-ray diffraction and differential scanning calorimetry. PAC was found to be in an amorphous state. The hyaluronic acid coated on the surface of mesoporous hollow alumina nanoparticles (MHA) regulated the drug release rate and the loaded samples obtained a sustained drug release. In vitro experiments demonstrated that paclitaxel-hyaluronic acid functionalized mesoporous hollow alumina nanoparticles (PAC-HMHA) had a high cellular uptake, which increased the drug level in tumor tissues and was beneficial to promote apoptosis. An in vivo tumor inhibition rate study demonstrated that PAC-HMHA (64.633 ± 4.389%) had a better antitumor effect than that of paclitaxel-mesoporous alumina nanoparticles (PAC-MHA, 56.019 ± 6.207%) and pure PAC (25.593 ± 4.115%). Therefore it can be concluded that PAC-HMHA are a prospective tumor-targeted delivery medium and can be useful for future cancer therapy.

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Ferulic Acid-Loaded Shellac Microparticles Prepared Using Electrohydrodynamic Atomization

Advanced Materials Research ◽

10.4028/www.scientific.net/amr.675.326 ◽

2013 ◽

Vol 675 ◽

pp. 326-330 ◽

Cited By ~ 3

Author(s):

Deng Guang Yu ◽

Wei Qian ◽

Xia Wang ◽

Ying Li ◽

Wei Jun Lu ◽

...

Keyword(s):

Drug Release ◽

Ferulic Acid ◽

Diffusion Mechanism ◽

Amorphous State ◽

Fickian Diffusion ◽

In Vitro Dissolution ◽

Release Time ◽

Infrared Analysis ◽

Sustained Drug Release ◽

Electrohydrodynamic Atomization

An Electrohydrodynamic atomization (EHDA) process was exploited to prepare ferulic acid (FA)-loaded shellac microparticles. SEM observations showed that all the particles were round and solid with their sizes gradually increased from 0.68 ± 0.21 to 2.75 ± 0.64 μm as the concentrations of shellac and FA in ethanol raised from 20% to 50% (w/v). Wide-angle X-ray diffraction analyses demonstrated that FA had been totally converted into an amorphous state in the shellac matrix microparticles. Attenuated total reflectance Fourier transform infrared analysis disclosed that the hydrogen bonding presented between FA and shellac molecules. In vitro dissolution tests verified that all the microparticles were able to provide a fine sustained drug release profile. The release time periods had a close relationship with the diameters of microparticles. All the microparticles released the loaded FA via a typical Fickian diffusion mechanism. The present study provides an easy way to develop novel drug delivery microparticles for providing sustained drug release profiles.

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Drug Sustained Release Multiple-Component Polymeric Microparticles Fabricated Using an Electrospray Process

Advanced Materials Research ◽

10.4028/www.scientific.net/amr.937.269 ◽

2014 ◽

Vol 937 ◽

pp. 269-275 ◽

Cited By ~ 2

Author(s):

Xiao Yan Li ◽

Deng Guang Yu ◽

Fa Ping Jiang ◽

Kong Jing Deng ◽

Zhi Du ◽

...

Keyword(s):

Drug Release ◽

Sustained Release ◽

Amorphous State ◽

Release Time ◽

Drug Release Profile ◽

Sustained Drug Release ◽

Electron Microscopic ◽

Polymeric Microparticles ◽

Multiple Component ◽

Release Profiles

The present study investigates the preparation of ferulic acid (FA) sustained-release cellulose acetate (CA) microparticles, in which a third component, polyvinylpyrrolidone (PVP), was included into the microcomposites for an improved sustained drug release profile. An electrospraying process was exploited for the fabrication of multiple-component microparticles. Under an applied voltage of 18 kV, FA/PVP/CA composite microparticles were successfully generated. Field emission scanning electron microscopic observations demonstrated that these microparticles had an indented surface morphology with an average diameter of 1.71 ± 0.56 μm. The drug presented in the polymeric microparticles in an amorphous state due to the favorable secondary interactions among the components, as verified by the X-ray diffraction (XRD) patterns and attenuated total reflectance Fourier transform spectra. The triple-component microparticles could provide a fine sustained release profiles with full release completeness and small tailing-off release time period. The electrospraying process is a useful tool for developing sustained release microparticles and multiple-component co-existence in the microparticles can be taken to adjust the sustained drug release profiles.

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The Development of Pemetrexed Diacid-Loaded Gelatin-Cloisite 30B (MMT) Nanocomposite for Improved Oral Efficacy Against Cancer: Characterization, In-Vitro and Ex-Vivo Assessment

Current Drug Delivery ◽

10.2174/1567201817666200210120231 ◽

2020 ◽

Vol 17 (3) ◽

pp. 246-256

Author(s):

Kriti Soni ◽

Ali Mujtaba ◽

Md. Habban Akhter ◽

Kanchan Kohli

Keyword(s):

Drug Release ◽

Oral Delivery ◽

Ex Vivo ◽

Confocal Laser ◽

Release Mechanism ◽

Scanning Calorimetry ◽

Sem Images ◽

Cloisite 30B ◽

Ft Ir

Aim: The intention of this investigation was to develop Pemetrexed Diacid (PTX)-loaded gelatine-cloisite 30B (MMT) nanocomposite for the potential oral delivery of PTX and the in vitro, and ex vivo assessment. Background: Gelatin/Cloisite 30 B (MMT) nanocomposites were prepared by blending gelatin with MMT in aqueous solution. Methods: PTX was incorporated into the nanocomposite preparation. The nanocomposites were investigated by Fourier Transmission Infra Red Spectroscopy (FT-IR), Differential Scanning Calorimetry (DSC), Scanning Electron Microscope (SEM) X-Ray Diffraction (XRD) and Confocal Laser Microscopy (CLSM). FT-IR of nanocomposite showed the disappearance of all major peaks which corroborated the formation of nanocomposites. The nanocomposites were found to have a particle size of 121.9 ± 1.85 nm and zeta potential -12.1 ± 0.63 mV. DSC thermogram of drug loaded nanocomposites indicated peak at 117.165 oC and 205.816 oC, which clearly revealed that the drug has been incorporated into the nanocomposite because of cross-linking of cloisite 30 B and gelatin in the presence of glutaraldehyde. Results: SEM images of gelatin show a network like structure which disappears in the nanocomposite. The kinetics of the drug release was studied in order to ascertain the type of release mechanism. The drug release from nanocomposites was in a controlled manner, followed by first-order kinetics and the drug release mechanism was found to be of Fickian type. Conclusion: Ex vivo gut permeation studies revealed 4 times enhancement in the permeation of drug present in the nanocomposite as compared to plain drug solution and were further affirmed by CLSM. Thus, gelatin/(MMT) nanocomposite could be promising for the oral delivery of PTX in cancer therapy and future prospects for the industrial pharmacy.

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The Correlation between Physical Crosslinking and Water-Soluble Drug Release from Chitosan-Based Microparticles

Pharmaceutics ◽

10.3390/pharmaceutics12050455 ◽

2020 ◽

Vol 12 (5) ◽

pp. 455

Author(s):

Emilia Szymańska ◽

Katarzyna Woś-Latosi ◽

Julia Jacyna ◽

Magdalena Dąbrowska ◽

Joanna Potaś ◽

...

Keyword(s):

Drug Release ◽

Polymer Matrix ◽

Drug Loading ◽

Water Soluble ◽

Dissolution Behavior ◽

Complex Nature ◽

Prolonged Release ◽

Scanning Calorimetry ◽

Burst Effect ◽

The Impact

Microparticles containing water-soluble zidovudine were prepared by spray-drying using chitosan glutamate and beta-glycerophosphate as an ion crosslinker (CF). The Box–Behnken design was applied to optimize the microparticles in terms of their drug loading and release behavior. Physicochemical studies were undertaken to support the results from dissolution tests and to evaluate the impact of the crosslinking ratio on the microparticles’ characteristics. The zidovudine dissolution behavior had a complex nature which comprised two phases: an initial burst effect followed with a prolonged release stage. The initial drug release, which can be modulated by the crosslinking degree, was primarily governed by the dissolution of the drug crystals located on the microparticles’ surfaces. In turn, the further dissolution stage was related to the drug diffusion from the swollen polymer matrix and was found to correlate with the drug loading. Differential Scanning Calorimetry (DSC) studies revealed the partial incorporation of a non-crystallized drug within the polymer matrix, which correlated with the amount of CF. Although CF influenced the swelling capacity of chitosan glutamate microparticles, surprisingly a higher amount of CF did not impact the time required for 80% of the drug to be released markedly. The formulation with the lowest polymer:CF ratio, 3:1, was selected as optimal, providing satisfactory drug loading and displaying a moderate burst effect within the first 30 min of the study, followed with a prolonged drug release of up to 210 min.

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Towards feedback-controlled nanomedicines for smart, adaptive delivery

Experimental Biology and Medicine ◽

10.1177/1535370218800456 ◽

2018 ◽

Vol 244 (4) ◽

pp. 283-293 ◽

Cited By ~ 4

Author(s):

Stephen J. Jones ◽

Annette F. Taylor ◽

Paul A Beales

Keyword(s):

Drug Delivery ◽

Drug Release ◽

Drug Delivery Systems ◽

Delivery Systems ◽

The Body ◽

Living Systems ◽

Prolonged Release ◽

Drug Bioavailability ◽

Drug Release Profile ◽

Chemical Systems

Nanomedicines for controlled drug release provide temporal and spatial regulation of drug bioavailability in the body. The timing of drug release is usually engineered either for slow gradual release over an extended period of time or for rapid release triggered by a specific change in its physicochemical environment. However, between these two extremes, there is the desirable possibility of adaptive nanomedicines that dynamically modulate drug release in tune with its changing environment. Adaptation and response through communication with its environment is a fundamental trait of living systems; therefore, the design of biomimetic nanomedicines through the approaches of bottom-up synthetic biology provides a viable route to this goal. This could enable drug delivery systems to optimize release in synchronicity with the body’s natural biological rhythms and the personalized physiological characteristics of the patient, e.g. their metabolic rate. Living systems achieve this responsiveness through feedback-controlled biochemical processes that regulate their functional outputs. Towards this goal of adaptive drug delivery systems, we review the general benefits of nanomedicine formulations, provide existing examples of experimental nanomedicines that encapsulate the metabolic function of enzymes, and give relevant examples of feedback-controlled chemical systems. These are the underpinning concepts that hold promise to be combined to form novel adaptive release systems. Furthermore, we motivate the advantages of adaptive release through chronobiological examples. By providing a brief review of these topics and an assessment of the state of the art, we aim to provide a useful resource to accelerate developments in this field. Impact statement The timing and rate of release of pharmaceuticals from advanced drug delivery systems is an important property that has received considerable attention in the scientific literature. Broadly, these mostly fall into two classes: controlled release with a prolonged release rate or triggered release where the drug is rapidly released in response to an environmental stimulus. This review aims to highlight the potential for developing adaptive release systems that more subtlety modulate the drug release profile through continuous communication with its environment facilitated through feedback control. By reviewing the key elements of this approach in one place (fundamental principles of nanomedicine, enzymatic nanoreactors for medical therapies and feedback-controlled chemical systems) and providing additional motivating case studies in the context of chronobiology, we hope to inspire innovative development of novel “chrononanomedicines.”

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