A Mechanistic Study of Ultrasonically‐Enhanced Transdermal Drug Delivery

Mitragotri, Samir; Edwards, David A.; Blankschtein, Daniel; Langer, Robert

doi:10.1002/jps.2600840607

Cited by 321 publications

(202 citation statements)

References 22 publications

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“…They concluded that the 1 MHz frequency showed a relatively higher transport than either 3 MHz or its topical application of the drug. Mitragotri et al [13] also reported that phonophoretic enhancement varies inversely with ultrasound frequency as frequency increases, the vibration amplitude decreases and absorption increases. Therefore, 1 MHz frequency ultrasound for aceclofenac gel phonophoresis was considered to be effective and adapted in this study.…”

Section: Discussionmentioning

confidence: 97%

Phonophoresis in temporomandibular joint disorders: A clinical trial

Vijayalakshmi¹,

Mubeen²,

Rajguru³

2015

JCRI

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Background and Objective: Temporomandibular joint disorders (TMDs) are identified as a major cause of non-dental pain in the orofacial region. An effective drug delivery into this complex joint can result in a good prognosis. Phonophoresis is a novel phenomenon that exponentially increases the absorption of topical pharmacological compounds and achieves effective therapeutic drug concentration at the target site. Hence, this study is designed to assess the feasibility and effectiveness of aceclofenac gel phonophoresis in the management of TMDs. Methods: Selected 60 patients were randomly divided into two equal groups. Group A were treated with aceclofenac gel phonophoresis and Group B with that of its topical application for 15 days. The scores of visual analog scale (VAS), maximum mouth opening, lateral and protrusive excursion, Helkimo anamnestic and clinical dysfunction index, erythrocyte sedimentation rate, and C-reactive protein were evaluated at baseline and 15 days after treatment. Results: Statistically significant increase in mean maximum mouth opening, lateral excursion and a significant reduction in scores of VAS, Helkimo anamnestic, and clinical dysfunction index were observed post-treatment in Group A as compared to Group B. Conclusions: Aceclofenac gel phonophoresis is feasible and effective in reduction of signs and symptoms of TMDs.

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Section: Discussionmentioning

confidence: 97%

Phonophoresis in temporomandibular joint disorders: A clinical trial

Vijayalakshmi¹,

Mubeen²,

Rajguru³

2015

JCRI

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“…Sometimes chemical enhancers were used to further increase the permeability [102][103][104]. However, no significant transport of protein could be achieved until 10 years ago when Mitrogotri et al showed that low frequency ultrasound was much more effective than higher frequencies and provided evidence as to the mechanism involved [102][103][104][105][106][107][108][109][110][111][112][113][114]. Skin permeability increased with decreasing frequency, and with increasing time of exposure and intensity (beyond a threshold), thus identifying collapse cavitation as a causative mechanism [105][106][107]110,111,115].…”

Section: Transdermal Protein Delivery-mentioning

confidence: 99%

“…The current theory is that cavitation events open reversible channels in the lipids layers of the stratum corneum and provide less tortuous paths of transport for proteins such as insulin [90,[105][106][107]110]. Electron microscopy on skin exposed to low frequency ultrasound revealed the removal of surface cells and the formation of large pores and pockets (~20 μm), large enough to accomodate transport of proteins and other large molecules [116][117][118][119].…”

Section: Transdermal Protein Delivery-mentioning

confidence: 99%

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Ultrasonic drug delivery – a general review

Pitt

Husseini

Staples

2004

Expert Opinion on Drug Delivery

546

428

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Ultrasound (US) has an ever-increasing role in the delivery of therapeutic agents including genetic material, proteins, and chemotherapeutic agents. Cavitating gas bodies such as microbubbles are the mediators through which the energy of relatively non-interactive pressure waves is concentrated to produce forces that permeabilize cell membranes and disrupt the vesicles that carry drugs. Thus the presence of microbubbles enormously enhances delivery of genetic material, proteins and smaller chemical agents. Delivery of genetic material is greatly enhanced by ultrasound in the presence of microbubbles. Attaching the DNA directly to the microbubbles or to gas-containing liposomes enhances gene uptake even further. US-enhanced gene delivery has been studied in various tissues including cardiac, vascular, skeletal muscle, tumor and even fetal tissue. US-enhanced delivery of proteins has found most application in transdermal delivery of insulin. Cavitation events reversibly disrupt the structure of the stratus corneum to allow transport of these large molecules. Other hormones and small proteins could also be delivered transdermally. Small chemotherapeutic molecules are delivered in research settings from micelles and liposomes exposed to ultrasound. Cavitation appears to play two roles: it disrupts the structure of the carrier vesicle and releases the drug; it also makes the cell membranes and capillaries more permeable to drugs. There remains a need to better understand the physics of cavitation of microbubbles and the impact that such cavitation has upon cells and drug-carrying vesicles.

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“…Passive permeability of drugs across the highly lipophilic stratum corneum is especially difficult to com-pounds which are hydrophilic, very lipophilic, of high molecular weight (MW > 400 g/mol) or charged (Vasil'ev et al, 2001;Wang et al, 2005). There have been many different approaches to overcome the skin barrier, including mechanical disruption (Mitragotri et al, 1995), chemical modification (Stoughton and Fritsch, 1964), electroporation and iontophoresis (Weaver et al, 1999). Iontophoresis has been reported as a promising answer for the effective transdermal drug delivery, especially for the novel biotechnologically developed drugs such as peptides and proteins that are hydrophillic, charged macromolecules and susceptible to proteolysis, chemical change and denaturation (Tabata and Ikada, 1998;Banga et al, 1999;Wang et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

pH- and electro-responsive characteristics of silk fibroin–hyaluronic acid polyelectrolyte complex membranes

Malay

Batıgün

Bayraktar

2009

International Journal of Pharmaceutics

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a b s t r a c t pH-responsiveness of recently developed silk fibroin (SF) and hyaluronic acid (HA) polyelectrolyte complex (PEC) membranes and their potential use in electro-responsive drug release systems were investigated. PEC membranes were prepared within a narrow pH window (3.0-3.5) for a SF-HA weight ratio of 20 and they were characterized by Atomic Force Microscopy in addition to characterization studies previously reported by our group. Swelling kinetics of the membranes was studied for a pH window of 2.5-7.4 and cyclic swelling test was performed to determine the pH-responsiveness of the membranes. It was shown that membranes swelled more in alkaline conditions and responded to variations in pH of the medium. Electric-stimuli assisted drug permeation and release studies were performed with a custom-made diffusion cell under both passive condition and electric field applied in pulsatile fashion. The instantaneous flux raised as the current was applied and then declined when the current application was terminated, and this process was repeated on subsequent applications. SF-HA complex membranes were found promising for the electric-stimuli-sensitive release of a high molecular weight and charged model drug for a membrane-permeation controlled formulation.

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A Mechanistic Study of Ultrasonically‐Enhanced Transdermal Drug Delivery

Cited by 321 publications

References 22 publications

Phonophoresis in temporomandibular joint disorders: A clinical trial

Phonophoresis in temporomandibular joint disorders: A clinical trial

Ultrasonic drug delivery – a general review

pH- and electro-responsive characteristics of silk fibroin–hyaluronic acid polyelectrolyte complex membranes

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