Avoiding a Sticky Situation: Bypassing the Mucus Barrier for Improved Local Drug Delivery

Zierden, Hannah C.; Josyula, Aditya; Shapiro, Rachel L.; Hsueh, Henry T.; Hanes, Justin; Ensign, Laura M.

doi:10.1016/j.molmed.2020.12.001

Cited by 56 publications

(38 citation statements)

References 100 publications

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“…Mucus affects drug permeability and absorption and is considered as one of the most formidable barriers for oral, GI, vaginal, nasal, ocular, and intravesical drug transport. [131] Consequently, a significant amount of research was focused on developing alternative muco-mimetic materials. [132] Incorporating mucus into these in vitro models should improve in vitro/in vivo correlation and hopefully reduce animal usage.…”

Section: Nasal Drug Deliverymentioning

confidence: 99%

Bioengineered Biomimetic and Bioinspired Noninvasive Drug Delivery Systems

Rahamim

Azagury

2021

Adv Funct Materials

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The main purpose herein is to provide an up-to-date review on noninvasive biomimetic, bioinspired, and bioengineered drug delivery system (DDS). Noninvasive DDS is an ever-growing field critical for the applicability of drugs. It offers noninvasive administration routes with improved controlled, targeted, and triggered drug delivery. Noninvasive DDS employ many approaches and strategies, such as, nano-and microparticles, lipid-based systems, sonophoresis, electrophoresis and iontophoresis, penetration enhancers, microneedles, and gels. The last decade seen a surge in research papers employing the paradigms of biomimicry, bioinspiration, and bioengineering. However, since the use of these terms in noninvasive DDS field is often inconsistent and unclear, some generalized perspectives are provided on the possible usage of these terms in future publications. Additionally, a critical discussion on the novelty and origins of these paradigms is provided. The advantages and disadvantages of each of the noninvasive routes and their current main limitations are summarized. The main aspects of indicated fields are discussed: The unique physiology of the related tissues, the main hurdles for mass transport, the various DDS tested, and materials selection. Finally, the basic concepts and therapeutic effects of these DDS are discussed and future venues for noninvasive biomimetic, bioinspired, and bioengineered DDS research are proposed.

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Section: Nasal Drug Deliverymentioning

confidence: 99%

Bioengineered Biomimetic and Bioinspired Noninvasive Drug Delivery Systems

Rahamim

Azagury

2021

Adv Funct Materials

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“…Nanoformulations permit the delivery of poorly water-soluble drugs across the pulmonary route, thereby improving drug bioavailability. The nanoparticles incorporated in the mucoadhesive polymeric formulations promote drug localization in the nasal cavity [ 10 ]. The use of mucoadhesive natural polymers as excipients along with the aerosolized drug nanoformulation prolong the retention of the latter in the respiratory tract after inhalation.…”

Section: Advantages Of Nanosize In Pulmonary Deliverymentioning

confidence: 99%

“…Pulmonary administration ensures rapid absorption of the administered drug due to high vascularization of the respiratory epithelia, in addition to bypassing first-pass metabolism. Nanosized, neutral drug-delivery vehicles efficiently penetrate through the airway mucus, whereas the delivery systems with a positive surface charge preferentially adhere to the negatively charged mucus mesh in a typical pulmonary delivery paradigm [ 10 ]. Importantly, the mucoadhesive delivery systems based on cationic polysaccharides, such as trimethyl chitosan, cationic cellulose and cationic starch, display a prolonged retention time in the airway epithelium, thereby ensuring optimal drug absorption at the target site.…”

Section: Mucoadhesive Polysaccharide Nanoparticles As Prospective Delivery Systems For Covid-19mentioning

confidence: 99%

Mucoadhesive Nanoformulations and Their Potential for Combating COVID-19

Prasher

Sharma

2021

Nanomedicine (Lond.)

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“… 24 An alternative approach that has been demonstrated for a wide variety of mucosal surfaces, including the eye, female reproductive tract, gastrointestinal tract, and airways is to formulate nanoparticles with mucoinert surface coatings. 25 , 26 These so‐called mucus‐penetrating particles (MPP) are nonadhesive to the sticky mucin proteins and small enough in size to fit through the net‐like pores, leading to enhanced delivery of small‐molecule drugs and nucleic acids alike. 25 In the context of eye drops, MPP provide rapid and enhanced intraocular drug absorption, leading to the Food and Drug Administration (FDA) approval of two loteprednol etabonate (LE)‐based products for treating ocular inflammation and pain.…”

Section: Introductionmentioning

confidence: 99%

“… 25 , 26 These so‐called mucus‐penetrating particles (MPP) are nonadhesive to the sticky mucin proteins and small enough in size to fit through the net‐like pores, leading to enhanced delivery of small‐molecule drugs and nucleic acids alike. 25 In the context of eye drops, MPP provide rapid and enhanced intraocular drug absorption, leading to the Food and Drug Administration (FDA) approval of two loteprednol etabonate (LE)‐based products for treating ocular inflammation and pain. 7 Here, we describe an approach for forming an insoluble ion‐paired complex of MOX with pamoic acid that can be formulated into a mucoinert nanosuspension (MOX–PAM NS).…”

Section: Introductionmentioning

confidence: 99%

An ion‐paired moxifloxacin nanosuspension eye drop provides improved prevention and treatment of ocular infection

Josyula

Omiadze

Parikh

et al. 2021

Bioengineering & Transla Med

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There are numerous barriers to achieving effective intraocular drug administration, including the mucus layer protecting the ocular surface. For this reason, antibiotic eye drops must be used multiple times per day to prevent and treat ocular infections. Frequent eye drop use is inconvenient for patients, and lack of adherence to prescribed dosing regimens limits treatment efficacy and contributes to antibiotic resistance.Here, we describe an ion-pairing approach used to create an insoluble moxifloxacinpamoate (MOX-PAM) complex for formulation into mucus-penetrating nanosuspension eye drops (MOX-PAM NS). The MOX-PAM NS provided a significant increase in ocular drug absorption, as measured by the area under the curve in cornea tissue and aqueous humor, compared to Vigamox in healthy rats. Prophylactic and treatment efficacy were evaluated in a rat model of ocular Staphylococcus aureus infection. A single drop of MOX-PAM NS was more effective than Vigamox, and completely prevented infection. Once a day dosing with MOX-PAM NS was similar, if not more effective, than three times a day dosing with Vigamox for treating Aditya Josyula and Revaz Omiadze contributed equally to this study.

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Avoiding a Sticky Situation: Bypassing the Mucus Barrier for Improved Local Drug Delivery

Cited by 56 publications

References 100 publications

Bioengineered Biomimetic and Bioinspired Noninvasive Drug Delivery Systems

Bioengineered Biomimetic and Bioinspired Noninvasive Drug Delivery Systems

Mucoadhesive Nanoformulations and Their Potential for Combating COVID-19

An ion‐paired moxifloxacin nanosuspension eye drop provides improved prevention and treatment of ocular infection

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