Bioadhesive Gel Research Articles

Design and evaluation of an intravesical delivery system for superficial bladder cancer: preparation of gemcitabine HCl-loaded chitosan-thioglycolic acid nanoparticles and comparison of chitosan/poloxamer gels as carriers.

This study aimed to develop an intravesical delivery system of gemcitabine HCl for superficial bladder cancer in order to provide a controlled release profile, to prolong the residence time, and to avoid drug elimination via urination. For this aim, bioadhesive nanoparticles were prepared with thiolated chitosan (chitosan–thioglycolic acid conjugate) and were dispersed in bioadhesive chitosan gel or in an in situ gelling poloxamer formulation in order to improve intravesical residence time. In addition, nanoparticle-loaded gels were diluted with artificial urine to mimic in vivo conditions in the bladder and were characterized regarding changes in gel structure. The obtained results showed that chitosanthioglycolic acid nanoparticles with a mean diameter of 174.5±3.762 nm and zeta potential of 32.100±0.575 mV were successfully developed via ionotropic gelation and that the encapsulation efficiency of gemcitabine HCl was nearly 20%. In vitro/ex vivo characterization studies demonstrated that both nanoparticles and nanoparticle-loaded chitosan and poloxamer gels might be alternative carriers for intravesical administration of gemcitabine HCl, prolonging its residence time in the bladder and hence improving treatment efficacy. However, when the gel formulations were diluted with artificial urine, poloxamer gels lost their in situ gelling properties at body temperature, which is in conflict with the aimed formulation property. Therefore, 2% chitosan gel formulation was found to be a more promising carrier system for intravesical administration of nanoparticles.

Preparation and characterization of bioadhesive controlled-release gels of cidofovir for vaginal delivery

The aim of this study was to develop mucoadhesive and thermosensitive gels for vaginal delivery that would be able to provide a controlled release of the model drug, cidofovir. The study also monitored the drug’s potential antiviral properties. Cidofovir was put into the form of a vaginal gel, using mucoadhesive and thermosensitive polymers such as chitosan, Carbopol 974P, HPMC, and poloxamer 407. The physicopharmaceutical properties and stability of the vaginal gel formulations were evaluated. The gel formulation which was prepared with HPMC K100M exhibited the highest viscosity, as well as maximum adhesiveness, cohesiveness, and mucoadhesion values. The results of antiviral activity studies, which used the bovine herpes virus type 1 virus infection in vitro model using Vero cells, demonstrated the antiherpetic effect of the cidofovir gel containing HPMC K100M, at least under in vitro conditions. The study found that a mucoadhesive vaginal gel containing cidofovir can be a promising and innovative alternative therapeutic system for the treatment of genital herpes simplex virus and human papilloma virus induced infections in women.

Double-blind, randomized pilot study of bioadhesive chlorhexidine gel in the prevention and treatment of mucositis induced by chemoradiotherapy of head and neck cancer.

BackgroundTo evaluate, in an initial way, the effectiveness of bioadhesive chlorhexidine gel 0.2% versus placebo as a preventive and therapeutic intervention of oral mucositis induced by radiation therapy and chemotherapy in patients diagnosed with head and neck cancer treated with chemoradiotherapy.Material and MethodsIn this pilot study, 7 patients (range of age: 18- 65), having histological documented diagnosis of squamous carcinoma on the head and neck region in stage III and IV, and receiving combined radiation treatment and chemotherapy (cisplatin 100 mg/m2 IV on days 1, 22, and 43 of irradiation) were studied. Simultaneously, a topical application was performed with bioadhesive chlorhexidine gel 0.2% in the study group, and the placebo gel for the control group in 5 applications per day, from the time of initiation of cancer treatment to 2 weeks after completion of chemo-radiotherapy treatment (11 weeks of follow-up). The gradation of mucositis, pain, analgesic consumption, infectious complications, and treatment tolerance was measured.ResultsAfter 7 patients completed the protocol, any differences were observed between groups in an interval analysis. Mucositis, pain, and tolerance was similar in both groups.ConclusionsOur results must be interpreted with caution due to the reduced sample size, but the use of bioadhesive chlorhexidine gel 0.2% didn’t contribute clinical improvement to the oral mucositis induced by radiation therapy and chemotherapy. Key words: Chlorhexidine, mucositis, head and neck cancer.

Effect of intra-alveolar placement of 0.2% chlorhexidine bioadhesive gel on the incidence of alveolar osteitis following the extraction of mandibular third molars. A double-blind randomized clinical trial.

Alveolar osteitis (AO) is a common complication after third molar surgery. One of the most studied agents in its prevention is chlorhexidine (CHX), which has proved to be effective. Objectives: The aim of this randomized double-blind clinical trial was to evaluate the efficacy of 0.2% bioadhesive chlorhexidine gel placed intra-alveolar in the prevention of AO after the extraction of mandibular third molars and to analyze the impact of risk factors such as smoking and oral contraceptives in the development of AO. Study Design: The study was a randomized, double-blind, clinical trial performed in the Ambulatory Surgery Unit of Hospital Vall d’Hebron and was approved by the Ethics Committee. A total of 160 patients randomly received 0.2% bioadhesive gel (80 patients) or bioadhesive placebo (80 patients). Results: 0.2% bioadhesive chlorhexidine gel applied in the alveolus after third molar extraction reduced the incidence of dry socket by 22% compared to placebo with differences that were not statistically significant. Smoking and the use of oral contraceptives were not related to higher incidence of dry socket. Female patients and the difficulty of the surgery were associated with a higher incidence of AO with statistically significant differences. 0.2% bioadhesive chlorhexidine gel did not produce any of the side effects related to chlorhexidine rinses. Conclusions: A 22% reduction of the incidence of alveolar osteitis with the application of 0.2% bioadhesive chlorhexidine gel compared to placebo with differences that were not statistically significant was found in this clinical trial. The lack of adverse reactions and complications related to chlorhexidine gel supports its clinical use specially in simple extractions and adds some advantages compared to the rinses in terms of duration of the treatment and reduction of staining and taste disturbance. Key words:Alveolar osteitis, dry socket, chlorhexidine bioadhesive gel, mandibular third molar surgery.

Effect of 0.2% Chlorhexidine Gel on Frequency of Dry Socket Following Mandibular Third Molar Surgery: A Double-Blind Clinical Trial Clinical Trial

Introduction: Alveolar osteitis (AO) is one of the most common postoperative complications after third molar surgery. Various techniques have been used to reduce the risk of AO. The aim of the current study was to evaluate the effect of Chlorhexidine (CHX) bioadhesive gel in preventing the development of AO. Methods: Patients with bilateral impacted mandibular third molars underwent surgical extraction of both teeth. One socket was randomly received CHX gel and the contralateral socket served as the control. The outcome variable was development of AO and the CHX gel application was the predictor variable. Data were analyzed using chi-square test with the confidence interval of 95%. Results: 41 patients (27 females and 14 males) with mean age of 24.15 ± 5.02 years underwent 82 surgeries. Total of 11 sockets (13.41%) developed AO. The frequency of AO in CHX gel (2 cases, 4.87%) side was significantly lower than control (9 cases, 21.95%) side (P-value < 0.05). No side effects observed following CHX gel application. Conclusion: Application of CHX gel could be an effective approach to reduce the risk of developing AO following mandibular third molar surgery.

In Vitro Liberation of Indomethacin from Chitosan Gels Containing Microemulsion in Different Dissolution Mediums

The objective of this research is to outline the liberation of indomethacin from different chitosan gels containing O/W microemulsion. The influence of surfactant, sodium lauryl sulfate, in two concentrations (0.5% and 0.75%, w/w) was determined in dissolution medium on the release of indomethacin, which was used as poor water-soluble model drug. Chitosan gels were prepared in four different concentrations of chitosan-1%, 1.5%, 2%, and 3% (w/w). Microemulsion enhanced the liberation of the indomethacin from chitosan gels into all dissolution mediums. Adding the surfactant into phosphate-buffered saline decreased the amount of liberated indomethacin from microemulsion, gel mixture, but increased the drug liberation from pure chitosan gels. It was detected that with the increased concentration of chitosan in the samples, the amount of indomethacin liberated (p < 0.05) also increased. A conclusion was drawn that the liberation of indomethacin from chitosan gels was influenced by increased pH of the samples. The high viscosity induced a higher release of indomethacin from 3% (w/w) chitosan hydrogel at pH 5.8 as compared with 3% (w/w) chitosan hydrogel at pH 3.8. The highest percentage of released indomethacin was determined when a mixture of microemulsion gel with higher chitosan content was used.

Prophylactic treatment with a novel bioadhesive gel formulation containing aciclovir and tenofovir protects from HSV-2 infection.

Over-the-counter access to an inexpensive, effective topical microbicide could reduce the transmission of HIV and would increase women's control over their health and eliminate the need to obtain their partners' consent for prophylaxis. Chronic infection with herpes simplex virus 2 (HSV-2), also known as human herpes virus 2, has been shown to facilitate HIV infection and speed the progression to immunodeficiency disease. Our objective is to develop a drug formulation that protects against both HSV-2 and HIV infection and adheres to the vaginal surface with extended residence time. We developed a formulation using two approved antiviral active pharmaceutical ingredients, aciclovir and tenofovir, in a novel bioadhesive vaginal delivery platform (designated SR-2P) composed of two polymers, poloxamer 407 NF (Pluronic(®) F-127) and polycarbophil USP (Noveon(®) AA-1). The efficacy of the formulation to protect from HSV-2 infection was tested in vitro and in vivo. In addition to its efficacy, it is essential for a successful microbicide to be non-irritating to the vaginal mucosa. We therefore tested our SR-2P platform gel in the FDA gold-standard microbicide safety model in rabbits and also in a rat vaginal irritation model. Our studies indicated that SR-2P containing 1% aciclovir and 5% tenofovir protects (i) Vero cells from HSV-2 infection in vitro and (ii) mice from HSV-2 infection in vivo. Our results further demonstrated that SR-2P was not irritating in either vaginal irritation model. We conclude that SR-2P containing aciclovir and tenofovir may be a suitable candidate microbicide to protect humans from vaginal HSV-2 infection.

Enfermedad periodontal en pacientes adolescentes con síndrome de Down. Presentación de caso

Down’s syndrome or trisomy 21 is man’s most frequent genetic disorder. It affects one out of 600-700 live births. It is characterized by the presence of an additional chromosome at the 21 pair which elicits generalized decrease of growth as well as intellectual disability. In scientific literature there are many reports of craniofacial and oral manifestations of this disorder. Chief oral condition reported in this group of patients is periodontal disease. ObjectiveEstablishment of preventive oral care for the development of periodontal disease in adolescent patients afflicted with Down’s syndrome. Case presentation15 year old Mexican-Indian male patient with trisomy 21. The patient was bilingual, afflicted with congenital heart disease, pulmonary hypertension and nephrotic syndrome. The patient equally presented ectopic dental eruption as well as congenital dental absences, Angle’s class III occlusion, anterior and posterior unilateral crossbite, oral respiration, labial eversion, fissured tongue and lips, clinodactyly and localized gingivitis. Behavior management was achieved with the «show-tell-do» technique alongside with voice control. Initial treatment consisted on sweeping brushing technique with parental assistance, use of dental floss (Dento Bacterial Plaque Control [DBPC]) (100%) as well as topical application of fluoride varnish. It was recommended to the parents they should use home applications of bioadhesive gel (Perioxidin®). After these measures, oral rehabilitation was undertaken. ConclusionsThe most relevant aspect of the treatment was the decrease (40%) in bacterial plaque reported in later control visits.

Identification of the viscoelastic properties of soft materials at low frequency: Performance, ill-conditioning and extrapolation capabilities of fractional and exponential models

We report about the experimental identification of viscoelastic constitutive models for frequencies ranging within 0–10Hz. Dynamic moduli data are fitted forseveral materials of interest to medical applications: liver tissue (Chatelin et al., 2011), bioadhesive gel (Andrews et al., 2005), spleen tissue (Nicolle et al., 2012) and synthetic elastomer (Osanaiye, 1996). These materials actually represent a rather wide class of soft viscoelastic materials which are usually subjected to low frequencies deformations.We also provide prescriptions for the correct extrapolation of the material behavior at higher frequencies. Indeed, while experimental tests are more easily carried out at low frequency, the identified viscoelastic models are often used outside the frequency range of the actual test.We consider two different classes of models according to their relaxation function: Debye models, whose kernel decays exponentially fast, and fractional models, including Cole–Cole, Davidson–Cole, Nutting and Havriliak–Negami, characterized by a slower decay rate of the material memory. Candidate constitutive models are hence rated according to the accurateness of the identification and to their robustness to extrapolation. It is shown that all kernels whose decay rate is too fast lead to a poor fitting and high errors when the material behavior is extrapolated to broader frequency ranges.

Evaluation of chitosan based vaginal bioadhesive gel formulations for antifungal drugs.

The aim of the present study was to evaluate chitosan as a vaginal mucoadhesive gel base for econazole nitrate and miconazole nitrate. To this aim, different types of chitosan with different molecular masses and viscosity properties [low molecular mass chitosan (viscosity: 20,000 mPa s), medium molecular mass chitosan (viscosity: 200,000 mPa s), high molecular mass chitosan (viscosity: 800,000 mPa s)] have been used. First, rheological studies were conducted on chitosan gels. Mechanical, syringeability and mucoadhesive properties of chitosan gels were determined. Release profiles of econazole nitrate and miconazole nitrate from chitosan gels were obtained and evaluated kinetically. In addition, anticandidal activities of formulations were determined. Finally, vaginal retention of chitosan gels in rats was evaluated by in vivo distribution studies. Based on the results, it can be concluded that gels prepared with medium molecular mass chitosan might be effectively used for different antifungal agents in the treatment of vaginal candidiosis, since it has high mucoadhesiveness, suitable mechanical and release properties with good vaginal retention.

Development, Characterization and in vivo Localization Study of Topical 5-Fluorouracil Gels: A Comparative Study with Conventional Formulation

5-Fluorouracil (5-FU) is one of the most effective antineoplastic agents used for the treatment of skin cancers and actinic keratosis (AK). Currently commercial formulation for topical 5-FU administration is available in the form of solution or cream. Commercial topical formulations are associated with the limitation of very short retention time at the administration site resulting in very poor skin permeation and deposition of drug. In the present study attempt was made for the preparation, optimization and characterization of bioadhesive gel formulations for localized delivery of 5-FU. Four bioadhesive gel formers, Carbopol 934, Carbopol 980, Methylcellulose (MC) and Poloxamer 188 were selected for the preparation of 5-FU bioadhesive gel formulations. The formulations were characterized for characteristic parameters including bioadhesive strength, skin deposition and interaction study. Carbopol 934 based bioadhesive gel formulation at the concentration of 1.5% w/w showed the best physicochemical properties such as viscosity (2670±12.2 cP), which was similar to the value obtained with the marketed cream (2870±14.4 cP), highest skin deposition (1290±56.4μg) and bioadhesive strength (18.62 gf). Cutaneous irritation of optimized bioadhesive gel formulations was also tested using the Draize test and only very slight erythema and no oedema was observed. In comparison, marketed formulation showed well defined erythema along with oedema formation. The result of the present study demonstrated that formulation of Carbopol 934 based 5-FU bioadhesive gel is a better alternative to the traditional cream base for enhanced topical delivery of 5-FU. The developed formulation will have the ease of application, better skin deposition and sustained release characteristic with reduced skin toxicity.

Topical Application of a Mucoadhesive Freeze-Dried Black Raspberry Gel Induces Clinical and Histologic Regression and Reduces Loss of Heterozygosity Events in Premalignant Oral Intraepithelial Lesions: Results from a Multicentered, Placebo-Controlled Clinical Trial

Approximately 30% higher grade premalignant oral intraepithelial neoplasia (OIN) lesions will progress to oral cancer. Although surgery is the OIN treatment mainstay, many OIN lesions recur, which is highly problematic for both surgeons and patients. This clinical trial assessed the chemopreventive efficacy of a natural product-based bioadhesive gel on OIN lesions. This placebo-controlled multicenter study investigated the effects of topical application of bioadhesive gels that contained either 10% w/w freeze-dried black raspberries (BRB) or an identical formulation devoid of BRB placebo to biopsy-confirmed OIN lesions (0.5 g × q.i.d., 12 weeks). Baseline evaluative parameters (size, histologic grade, LOH events) were comparable in the randomly assigned BRB (n = 22) and placebo (n = 18) gel cohorts. Evaluative parameters were: histologic grade, clinical size, and LOH. Topical application of the BRB gel to OIN lesions resulted in statistically significant reductions in lesional sizes, histologic grades, and LOH events. In contrast, placebo gel lesions demonstrated a significant increase in lesional size and no significant effects on histologic grade or LOH events. Collectively, these data strongly support BRB's chemopreventive impact. A cohort of very BRB-responsive patients, as demonstrated by high therapeutic efficacy, was identified. Corresponding protein profiling studies, which demonstrated higher pretreatment levels of BRB metabolic and keratinocyte differentiation enzymes in BRB-responsive lesions, reinforce the importance of local metabolism and differentiation competency. Results from this trial substantiate the LOH reductions identified in the pilot BRB gel study and extend therapeutic effects to significant improvements in histologic grade and lesional size.

A novel surfactant aided micellar system of oxidation inhibitors in clotrimazole bioadhesive gel: development, characterization, in vitro and in vivo antifungal evaluation against Candida clinical isolates

Clotrimazole (CLZ) is a widely used antifungal agent with poor aqueous solubility, which requires the development of new delivery systems to improve its therapeutic activity.

Design expert assisted formulation of topical bioadhesive gel of sertaconazole nitrate.

The objective of this work was to develop a bioadhesive topical gel of sertaconazole nitrate with the help of response-surface approach. Experiments were performed according to a 3-level factorial design to evaluate the effects of two independent variables [amount of Carbapol 934 = X1) and Sodium carboxymethylcellulose (NaCMC) = X2)] on the bioadhesive character of gel, rheological property of gel (consistency index), and in-vitro drug release. The best model was selected to fit the data. Mathematical equation was generated by Design Expert® software for the model which assists in determining the effect of independent variables. Response surface plots were also generated by the software for analyzing effect of the independent variables on the response. The effect of formulation variables on the product characteristics can be easily predicted and precisely interpreted by using a 3-level factorial design and generated quadratic mathematical equations. On the basis of product characteristics viscosity, bioadhesiveness, permeation study, in-vitro release, in-vivo studies, TPA and spreadability it can be concluded that the best batch of topical bioadhesive gel of Sertaconazole nitrate would be with 1% Carbopol 934 and 1% NaCMC.

The ability of retention, drug release and rheological properties of nanogel bioadhesives based on cellulose derivatives

The rheological and drug release behavior of biopolymer nanocomposite gels based on the cellulose derivatives, formulated as the bioadhesive drug delivery platforms, were investigated. The bioadhesive gel is composed of the microcrystalline cellulose, sodium carboxymethyl cellulose and phosphate buffered saline (pH = 7.4 at 20 °C) as the dissolution and release medium. The reinforcing nanofillers such as MMT-clay, fumed porous silica and porous starch were used as additives in the nanogel bioadhesive. The constant steady state viscosities of this nanogels upon incorporation of various nanofillers into the systems is the sign of structural stability. Hence, this system is suitable for use in the controlled drug delivery systems in contact with the biological tissues. Based on the rheological measurements, the shear flow properties (i.e. zero shear viscosity and yield stress) were influenced by the concentration of polymers and nanoparticles. The results indicate that the nonlinear rheological data are fitted properly by the Giesekus model. Furthermore, the results showed that the nonlinear viscoelastic parameters (λ and α) are highly affected by the biogel and nanoparticles concentrations. Finally, the drug release was measured, and the results indicated that the biopolymer-clay nanocomposites have appropriate release pattern as the release is better controlled compared to the other nanogel formulations.

Development of long-acting bioadhesive vaginal gels of oxybutynin: Formulation, in vitro and in vivo evaluations

Overactive bladder (OAB) and vaginal dryness are common problems after menopause. Oxybutynin (OXY) is an antimuscarinic agent that has been available for more than 30 years in the treatment of OAB patients. The aim of the work reported in this paper was to develop long acting mucoadhesive gel formulations of OXY and to investigate their effects on blood levels compared to those of oral OXY immediate release tablets, in rabbits. Mucoadhesive gels were prepared with chitosan, hydroxypropyl methylcellulose (HPMC K100M) and Poloxamer 407 (Pluronic F 127). The physicopharmaceutical properties of gels were evaluated. The gel formulation which was prepared with HPMC K100M, exhibited the highest viscosity, the greatest adhesiveness, cohesiveness and mucoadhesion values. The formulation which was prepared from HPMC K100M showed suitable permeation characteristics across the vaginal mucosa. Comparative bioavailability studies were carried out on rabbits with vaginal HPMC gel, vaginal chitosan gel, vaginal OXY solution and commercially available oral Üropan tablets. It was concluded that the highest AUC and relative bioavailability values were obtained for the bioadhesive vaginal gel formulation prepared with HPMC K100M. Therefore, the mucoadhesive vaginal gels of OXY can be a promising and innovative alternative therapeutic system for the treatment of OAB. It can be safely used in cases of overactive bladder and as well as vaginal dryness after menopause.

Considerations in selecting rapid-onset opioids for the management of breakthrough pain

Correspondence: Suzan Leake Archimedes Pharma, One Crossroads Drive, Bedminister, NJ 07921, USA Email suzanleake@archimedespharma.com Dear editor We read with great interest the recent publication by Smith. This article provides a valuable perspective on the selection of an agent to manage breakthrough pain. Smith recognizes the importance of a fast onset-of-action and the identification by Farrar et al of a 33% (often $2 point) change in the pain intensity difference as a measure of a ‘clinically important improvement’. For these reasons, Smith focuses on the various transmucosal fentanyl formulations that offer a rapid onset and he provides a nice summary of the key features of each of the available products. Smith also provides some ‘advantages and disadvantages’ of different routes of administration which can be used to select an appropriate formulation for an individual patient. We agree with much of the commentary presented, but feel that the grouping of dissimilar formulations based on route of administration is potentially too simple. For example, Smith includes two different products in the intranasal route discussion, despite earlier recognition of key formulation differences, and in doing so allocates weaknesses of one formulation to the other. We would like to inform readers of three important points regarding one intranasal fentanyl formulation: • First, fentanyl pectin nasal spray (Lazanda/PecFent Archimedes Development Ltd, Nottingham, UK) includes the unique PecSys technology that forms a bioadhesive gel on the nasal mucosa, which significantly reduces run-off/drip compared with a simple solution. This means that the fentanyl is retained in the nasal cavity and that variable absorption associated with nasal drip or swallowing is not an issue for fentanyl pectin nasal spray. Other formulations (nasal and oral) explicitly acknowledge in their prescribing information, the potential for variable absorption. • Secondly, the absorption of fentanyl from fentanyl pectin nasal spray has been specifically studied in patients with rhinitis; in that setting the absorption of fentanyl was not affected by nasal inflammation (area under the curve from time 0 to time of last quantifiable plasma concentration, area under the curve from time 0 to 1 hour after administration, maximum plasma concentration, and time to maximum plasma concentration) – which by implication suggests that patients with colds or illnesses that result in changes to the nasal mucosa are suitable candidates for fentanyl pectin nasal spray. • Finally, data from fentanyl pectin nasal spray Phase III trials show that patients did not have difficulty using the spray device; in fact the vast majority reported a high degree of satisfaction. Dovepress

MICROSPHERES AS AN OCULAR DRUG DELIVERY SYSTEM- A REVIEW

Ophthalmic drug delivery is most interesting and challenging delivery system facing the pharmaceutical scientist. The anatomy, physiology, and biochemistry of the eye render this organ highly impervious to foreign substances. A significant challenge to the formulator is to circumvent the protective barriers of the eye without causing permanent tissue damage. These barriers affect the bioavailability of drugs. Development of newer, more sensitive diagnostic techniques and novel therapeutic agents continue to provide ocular delivery systems with high therapeutic efficacy. These includes iontophoresis, liposome bioadhesive gels, ocular insert, contact lenses, liposomes & a special one is microspheres. Microsphere is a well designed controlled drug delivery system can overcome some of the problems of conventional therapy and enhance the therapeutic efficacy of a given drug. This approach delivering a therapeutic substance to the target site in a sustained controlled release fashion & achive a good bioavalability in ocular delivery system.

Effects of Intra-alveolar Placement of 0.2% Chlorhexidine Bioadhesive Gel on Dry Socket Incidence and Postsurgical Pain: A Double-Blind Split-Mouth Randomized Controlled Clinical Trial

To assess the effects of intra-alveolar application of chlorhexidine gel on the incidence of alveolar osteitis (dry socket) and the severity of postsurgical pain. A total of 160 impacted mandibular third molars were extracted in 80 patients enrolled in this trial. In each subject, a socket was randomly selected and packed to the crest of the alveolar ridge with a gelatin sponge dressing saturated in 0.2% chlorhexidine gel. The contralateral socket was packed with a dry dressing as the placebo. None of the included patients took antibiotics or analgesics. The occurrence of dry socket and patients' pain levels were assessed at the first and third postoperative days. The data were analyzed using Spearman correlation coefficient, McNemar, Wilcoxon, and chi-square tests. Chlorhexidine gel significantly reduced dry socket incidence from 32.6% to 11.3% (P ≤ .001 [McNemar and chi-square], absolute risk reduction = 21.2%, relative risk reduction = 65.4%, odds ratio = 0.263, relative risk = 0.345). It also significantly relieved postoperative pain on both sides in all the patients (P ≤ .001 [Wilcoxon]) and also in the 54 subjects who did not develop dry socket (P ≤ .001 [Wilcoxon]). Besides decreasing the incidence of dry socket, chlorhexidine gel can reduce postsurgical pain in patients with and without dry socket.

Painting blood vessels and atherosclerotic plaques with an adhesive drug depot.

The treatment of diseased vasculature remains challenging, in part because of the difficulty in implanting drug-eluting devices without subjecting vessels to damaging mechanical forces. Implanting materials using adhesive forces could overcome this challenge, but materials have previously not been shown to durably adhere to intact endothelium under blood flow. Marine mussels secrete strong underwater adhesives that have been mimicked in synthetic systems. Here we develop a drug-eluting bioadhesive gel that can be locally and durably glued onto the inside surface of blood vessels. In a mouse model of atherosclerosis, inflamed plaques treated with steroid-eluting adhesive gels had reduced macrophage content and developed protective fibrous caps covering the plaque core. Treatment also lowered plasma cytokine levels and biomarkers of inflammation in the plaque. The drug-eluting devices developed here provide a general strategy for implanting therapeutics in the vasculature using adhesive forces and could potentially be used to stabilize rupture-prone plaques.