Local delivery of imiquimod in hamsters using mucoadhesive films and their residence time in human patients

Ramineni, Sandeep K.; Dziubla, Thomas D.; Cunningham, Larry L.; Puleo, David A.

doi:10.1016/j.oooo.2014.08.015

Cited by 18 publications

(17 citation statements)

References 30 publications

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“…OSCC encompasses 90% of all oral malignancies 1, 3. Available treatment options include surgical resection, radiation, and chemotherapy.…”

Section: Discussionmentioning

confidence: 99%

“…Oral squamous cell carcinoma (OSCC) has historically been treated with surgery or radiation with or without chemotherapy, all of which lead to significant posttreatment morbidity 1 . Topical imiquimod cream has been approved by the Food and Drug Administration for treatment of nonhyperkeratotic actinic keratosis, superficial basal cell carcinoma, and external genital warts.…”

Section: Introductionmentioning

confidence: 99%

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Topical imiquimod for the palliative treatment of recurrent oral squamous cell carcinoma

2017

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“…OSCC encompasses 90% of all oral malignancies 1, 3. Available treatment options include surgical resection, radiation, and chemotherapy.…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Topical imiquimod for the palliative treatment of recurrent oral squamous cell carcinoma

2017

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“…It is critical to retain delivery system in the affected site for sufficient time to achieve desired local chemoprevention efficacy . To address these challenges, different mucoadhesive systems have been developed and evaluated . Films and patches are novel (can be trimmed to any shape or size), flexible, patient‐friendly, and convenient systems for local and systemic drug delivery applications .…”

Section: Advances In Drug Delivery Systemsmentioning

confidence: 99%

“…Aldara cream has also been effective in treating precancerous lesions of the oral cavity . Ramineni et al developed and evaluated polyvinylpyrrolidone (PVP) and carboxymethylcellulose (CMC) blend mucoadhesive films for improved intraoral site‐specific delivery of imiquimod . Imiquimod is a hydrophobic drug with poor water solubility.…”

Section: Advances In Drug Delivery Systemsmentioning

confidence: 99%

“…The PVP content also affected the polymer erosion and drug‐release characteristics (greater polymer erosion and higher drug release with increasing content of PVP) . Importantly, PVP/CMC films have been shown to exhibit excellent residence time in the mouth (4–8 h in hamsters and up to 4 h humans) and provide improved mucosal permeation and tissue localization of imiquimod without systemic exposure …”

Section: Advances In Drug Delivery Systemsmentioning

confidence: 99%

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Polymeric drug delivery systems for intraoral site‐specific chemoprevention of oral cancer

Desai

2017

J Biomed Mater Res

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Oral cancer is among the most prevalent cancers in the world. Moreover, it is one of the major health problems and causes of death in many regions of the world. The traditional treatment modalities include surgical removal, radiation therapy, systemic chemotherapy, or a combination of these methods. In recent decades, there has been significant interest in intraoral site-specific chemoprevention via local drug delivery using polymeric systems. Because of its easy accessibility and clear visibility, the oral mucosa is amenable for local drug delivery. A variety of polymeric systems-such as gels, tablets, films, patches, injectable systems (e.g., millicylindrical implants, microparticles, and in situ-forming depots), and nanosized carriers (e.g., polymeric nanoparticles, nanofibers, polymer-drug conjugates, polymeric micelles, nanoliposomes, nanoemulsions, and polymersomes)-have been developed and evaluated for the local delivery of natural and synthetic chemopreventive agents. The findings of in vitro, ex vivo, and in vivo studies and the positive outcome of clinical trials demonstrate that intraoral site-specific drug delivery is an attractive, highly effective and patient-friendly strategy for the management of oral cancer. Intraoral site-specific drug delivery provides unique therapeutic advantages when compared to systemic chemotherapy. Moreover, intraoral drug delivery systems are self-administrable and can be removed when needed, increasing patient compliance. This article covers important aspects and advances related to the design, development, and efficacy of polymeric systems for intraoral site-specific drug delivery. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1383-1413, 2018.

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Design and Testing of Efficient Mucus‐Penetrating Nanogels—Pitfalls of Preclinical Testing and Lessons Learned

Charbaji

Kar

Theune

et al. 2021

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Mucosal surfaces pose a challenging environment for efficient drug delivery. Various delivery strategies such as nanoparticles have been employed so far; yet, still yielding limited success. To address the need of efficient transmucosal drug delivery, this report presents the synthesis of novel disulfide‐containing dendritic polyglycerol (dPG)‐based nanogels and their preclinical testing. A bifunctional disulfide‐containing linker is coupled to dPG to act as a macromolecular crosslinker for poly‐N‐isopropylacrylamide (PNIPAM) and poly‐N‐isopropylmethacrylamide (PNIPMAM) in a precipitation polymerization process. A systematic analysis of the polymerization reveals the importance of a careful polymer choice to yield mucus‐degradable nanogels with diameters between 100 and 200 nm, low polydispersity, and intact disulfide linkers. Absorption studies in porcine intestinal tissue and human bronchial epithelial models demonstrate that disulfide‐containing nanogels are highly efficient in overcoming mucosal barriers. The nanogels efficiently degrade and deliver the anti‐inflammatory biomacromolecule etanercept into epithelial tissues yielding local anti‐inflammatory effects. Over the course of this work, several problems are encountered due to a limited availability of valid test systems for mucosal drug‐delivery systems. Hence, this study also emphasizes how critical a combined and multifaceted approach is for the preclinical testing of mucosal drug‐delivery systems, discusses potential pitfalls, and provides suggestions for solutions.

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Local delivery of imiquimod in hamsters using mucoadhesive films and their residence time in human patients

Cited by 18 publications

References 30 publications

Topical imiquimod for the palliative treatment of recurrent oral squamous cell carcinoma

Topical imiquimod for the palliative treatment of recurrent oral squamous cell carcinoma

Polymeric drug delivery systems for intraoral site‐specific chemoprevention of oral cancer

Design and Testing of Efficient Mucus‐Penetrating Nanogels—Pitfalls of Preclinical Testing and Lessons Learned

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