Mechanisms of deformable nanovesicles based on insulin-phospholipid complex for enhancing buccal delivery of insulin

Xu, You; Zhang, Xing; Zhang, Yun; Ye, Jun; Wang, Hongliang; Xia, Xuejun; Liu, Yuling

doi:10.2147/ijn.s175425

Cited by 27 publications

(32 citation statements)

References 30 publications

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“…Similar differences in the interaction of the mucosa with nanoparticles of opposite charges were observed by Chaves et al (2017). However, other studies have reported that cationic nanoparticles interacted more with the mucus and exhibited lower mucosal permeability in comparison to anionic nanoparticles (Chen et al, 2010; Yuan et al, 2011; Mouftah et al, 2016; Patil and Devarajan, 2016; Xu et al, 2018). This is also supported by studies in the lower gastrointestinal tract, whereby electrostatic interaction between cationic nanoparticles and the negatively charged mucins impeded the transport of the nanoparticles through the mucus layer (Hua et al, 2015).…”

Section: Nanoparticulate Drug Delivery Approachessupporting

confidence: 70%

“…Firstly, the physicochemical properties of the nanoparticles themselves (e.g., size, charge, composition, and surface properties) for optimal interaction with the sublingual or buccal mucosa. A number of different nanoparticulate systems have been evaluated for sublingual and buccal drug delivery, with polymer-based and lipid-based compositions being the most common (He et al, 2009; Roblegg et al, 2012; Teubl et al, 2013; Teubl et al, 2015; Mouftah et al, 2016; Patil and Devarajan, 2016; Chaves et al, 2017; Xu et al, 2018). The composition and structure of nanoparticles can be designed to confer a number of different properties, including mucoadhesion, bioadhesion, mucus-penetration, controlled release, and deformability (Hua et al, 2015).…”

Section: Nanoparticulate Drug Delivery Approachesmentioning

confidence: 99%

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Advances in Nanoparticulate Drug Delivery Approaches for Sublingual and Buccal Administration

Hua¹

2019

Front. Pharmacol.

119

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The sublingual and buccal routes of administration have significant advantages for both local and systemic drug delivery. They have shown to be an effective alternative to the traditional oral route, especially when fast onset of action is required. Drugs can be rapidly and directly absorbed into the systemic circulation via venous drainage to the superior vena cava. Therefore, they are useful for drugs that undergo high hepatic clearance or degradation in the gastrointestinal tract, and for patients that have swallowing difficulties. Drugs administered via the sublingual and buccal routes are traditionally formulated as solid dosage forms (e.g., tablets, wafers, films, and patches), liquid dosage forms (e.g., sprays and drops), and semi-solid dosage forms (e.g., gels). Conventional dosage forms are commonly affected by physiological factors, which can reduce the contact of the formulation with the mucosa and lead to unpredictable drug absorption. There have been a number of advances in formulation development to improve the retention and absorption of drugs in the buccal and sublingual regions. This review will focus on the physiological aspects that influence buccal and sublingual drug delivery and the advances in nanoparticulate drug delivery approaches for sublingual and buccal administration. The clinical development pipeline with formulations approved and in clinical trials will also be addressed.

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Section: Nanoparticulate Drug Delivery Approachessupporting

confidence: 70%

Section: Nanoparticulate Drug Delivery Approachesmentioning

confidence: 99%

Advances in Nanoparticulate Drug Delivery Approaches for Sublingual and Buccal Administration

Hua¹

2019

Front. Pharmacol.

119

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“…The particle sizes were 82.55 ± 3.85 nm with a narrow size distribution indicated by PDI < 0.200. The entrapment efficiency and deformability index of IPC-DNVs were 79.29% ± 2.41% and 38.25 ± 1.38 g/cm 2 /s ( n = 3) before lyophilization, respectively [29]. TEM micrographs of IPC-DNVs confirmed their spherical shape and whorl-like structure (Figure 2A).…”

Section: Resultsmentioning

confidence: 99%

“…IPC-DNVs were prepared using a thin-film hydration method, as described in our previous studies [28,29]. Briefly, 60 mg insulin and 600 mg phospholipid were independently dissolved in 6mL 0.1% trifluoroacetic acid–methanol and 60 mL dichloromethane, respectively.…”

Section: Methodsmentioning

confidence: 99%

Stabilization of Deformable Nanovesicles Based on Insulin-Phospholipid Complex by Freeze-Drying

Guo

Yang

et al. 2019

Pharmaceutics

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Deformable nanovesicles have been extensively investigated due to their excellent ability to penetrate biological barriers. However, suffering from serious physical and chemical instabilities, the wide use of deformable nanovesicles in medical applications is still limited. Moreover, far less work has been done to pursue the lyophilization of deformable nanovesicles. Here, we aimed to obtain stable deformable nanovesicles via freeze-drying technology and to uncover the underlying protection mechanisms. Firstly, the density of nanovesicles before freeze-drying, the effect of different kinds of cryoprotectants, and the types of different reconstituted solvents after lyophilization were investigated in detail to obtain stable deformable nanovesicles based on insulin-phospholipid complex (IPC-DNVs). To further investigate the underlying protection mechanisms, we performed a variety of analyses. We found that deformable nanovesicles at a low density containing 8% lactose and trehalose in a ratio of 1:4 (8%-L-T) have a spherical shape, smooth surface morphology in the lyophilized state, a whorl-like structure, high entrapment efficiency, and deformability after reconstitution. Importantly, the integrity of IPC, as well as the secondary structure of insulin, were well protected. Accelerated stability studies demonstrated that 8%-L-T remained highly stable during storage for 6 months at 25 °C. Based on in vivo results, lyophilized IPC-DNVs retained their bioactivity and had good efficacy. Given the convenience of preparation and long term stability, the use of combined cryoprotectants in a proper ratio to protect stable nanovesicles indicates strong potential for industrial production.

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“…A J o u r n a l P r e -p r o o f mean particle size of 148 nm, zeta potential of 15.5 mV, PdI of 0.26 and an association efficiency of 97.56% were observed. Insulin was also conjugated with phosphate and encapsulated in flexible nanovesicles for buccal drug delivery by Xu et al [64]. The formulation had a mean particle size of 85.84 ± 2.38 nm and a zeta potential -26.2 ± 0.5 mV, and the deformability was also assessed.…”

Section: Recent Studies Carried Out By Mahdizadeh Barzoki Et Al Propmentioning

confidence: 99%

Novel and revisited approaches in nanoparticle systems for buccal drug delivery

Macedo

Castro

Roque

et al. 2020

Journal of Controlled Release

106

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The buccal route is considered patient friendly due to its non-invasive nature and ease of administration. Such delivery route has been used as an alternative for the delivery of drugs that undergo first-pass metabolism or are susceptible to pH and enzymatic degradation, such as occurs in the gastrointestinal tract. However, the drug concentration absorbed in the buccal mucosa is often low to obtain an acceptable therapeutic effect, mainly due to the saliva turnover, tongue and masticatory movements, phonation, enzymatic degradation and lack of epithelium permeation.Therefore, the encapsulation of drugs into nanoparticles is an important strategy to avoid such problems and improve their buccal delivery. Different materials from lipids to natural or synthetic polymers and others have been used to protect and deliver drugs in a sustained, controlled or targeted manner, and enhance their uptake through the buccal mucosa improving their bioavailability and therapeutic outcome. Overall, the main aim of this review is to perform an overview about the nanotechnological approaches developed so far to improve the buccal delivery of drugs. Herein, several types of nanoparticles and delivery strategies are addressed, and a special focus on pipeline products is also given.

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Mechanisms of deformable nanovesicles based on insulin-phospholipid complex for enhancing buccal delivery of insulin

Cited by 27 publications

References 30 publications

Advances in Nanoparticulate Drug Delivery Approaches for Sublingual and Buccal Administration

Advances in Nanoparticulate Drug Delivery Approaches for Sublingual and Buccal Administration

Stabilization of Deformable Nanovesicles Based on Insulin-Phospholipid Complex by Freeze-Drying

Novel and revisited approaches in nanoparticle systems for buccal drug delivery

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