[A two-dimensional photographic and three-dimensional digital dental model comparative analysis in maxillary anterior teeth].

Objective: To assess the accuracy of two-dimensional (2D) photographs in measuring esthetic parameters of the maxillary anterior teeth by comparing them with measurements obtained from three-dimensional (3D) dental models. Methods: A total of one hundred volunteers (49 males, 51 females, aged 18-23 years) were recruited from School and Hospital of Stomatology, Wuhan University from January to February 2024. 3D digital models of their dentitions were obtained using an intraoral scanner, and standardized frontal 2D intraoral photographs were captured with a digital camera. The lengths, widths and width/length ratio of the bilateral incisors, lateral incisors and canines were measured on both the 3D digital models and the 2D intraoral photographs. The width ratios of adjacent maxillary anterior were also calculated on the 2D intraoral photographs and the frontal view of 3D digital models. Results: The widths of lateral incisors [(5.85±0.60) mm] and canines [(4.73±0.71) mm] and the lengths of canines [(8.72±0.96) mm] in the 2D intraoral photographs were significantly lower than those in 3D digital models [(6.65±0.59), (7.76±0.60), (8.90±0.86) mm] (t=-18.24, P<0.001; t=-54.43, P<0.001; t=-4.40, P<0.001), while there were no significant differences in the lengths and widths of the other teeth (P>0.05). The width/length ratios measured from the 2D intraoral photographs for the lateral incisors and canines (0.74±0.08, 0.55±0.08) were significantly lower than those measured in the 3D digital models (0.84±0.09, 0.88±0.09) (t=-19.68, P<0.001; t=-50.21, P<0.001), and the width/length ratio of the central incisors showed no significant difference between the two groups (P>0.05). The width ratios of canines/lateral incisors and lateral incisors/central incisors measured on the 2D intraoral photographs (0.72±0.06, 0.85±0.11) were significantly smaller than those measured in the frontal view of 3D digital models (0.75±0.06, 0.89±0.11) (t=-9.31, P<0.001; t=-6.58, P<0.001). Conclusions: There is a difference between 2D and 3D measurement results of teeth in the esthetic area and the magnitude of the difference varies with their position in the dental arch. When analyzing the measurement of the anterior teeth, it is necessary to choose the appropriate method according to the target tooth position.

[Minimally invasive liver surgery:progress in the last decade and evolving trends].

With the promotion and popularity of minimally invasive surgery and instruments,minimally invasive technologies have been widely used in the diagnosis and treatment of liver disease. In the past decade,with the development of relevant instruments,improvement of skills,and perfection of theories,the concept of individualized minimal invasion and precision has been popularized. Minimally invasive liver surgery is moving toward the goal of innovation-driven high-quality development.

[Application of membrane anatomy in hepatopancreatobiliary and splenic surgery].

Understanding of a variety of membranous structures throughout the body,such as the fascia,the serous membrane,is of great importance to surgeons. This is especially valuable in abdominal surgery. With the rise of membrane theory in recent years,membrane anatomy has been widely recognized in the treatment of abdominal tumors,especially of gastrointestinal tumors. In clinical practice. The appropriate choice of intramembranous or extramembranous anatomy is appropriate to achieve precision surgery. Based on the current research results,this article described the application of membrane anatomy in the field of hepatobiliary surgery,pancreatic surgery,and splenic surgery,with the aim of blazed the path from modest beginnings.

Decreased serum voriconazole levels caused by hepatic enzyme induction after rifapentine discontinuation: a case report and literature review.

BACKGROUND: Rifapentine is a rifamycin with unique bactericidal activity against Mycobacterium tuberculosis. It is also a potent inducer of CYP3A activity. However, the duration of rifapentine-induced hepatic enzyme activity after withdrawal is unclear. CASE REPORT: We report a case of a patient with Aspergillus meningitis treated with voriconazole after discontinuing rifapentine. Within ten days of rifapentine discontinuation, serum levels of voriconazole failed to reach the effective treatment range. CONCLUSIONS: Rifapentine is a potent inducer of hepatic microsomal enzymes. The induction of hepatic enzymes may exceed ten days after rifapentine discontinuation. Clinicians should be reminded of residual enzyme induction by rifapentine, especially when treating critically ill patients.

[Self-reported quality of life in patients with coronary heart disease and analysis of the associated factors].

Objective: To investigate the quality of life and associated factors in patients with coronary heart disease (CHD) in China. Methods: A cross-sectional study of 25 provinces and cities in China was performed from June to September 2020. A questionnaire was used to collect the socio-demographic and clinical information of patients with CHD, while the European Five-dimensional Quality of Life Scale (EQ-5D) was used to assess the quality of life. Multiple linear regression model was performed to analyze the associated factors. Results: The median age of the 1 075 responders was 60 (52, 67) years, and 797 (74.1%) were men. The EQ-5D and EQ-VAS indices were 0.7 (0.5, 0.8) and 60.0 (40.0, 80.0). Among the five dimensions in the quality of life scale, the frequency of anxiety/depression was the highest (59.8%), while problems in self-care was the lowest (35.8%). In the multiple linear regression model, female, increasing age, obesity, comorbidity(ies), anxiety/depression, social media channels, and receiving the CABG therapy were associated with the lower EQ-5D index (all P<0.05). In addition, increasing age, obesity, comorbidity (ies), depression, anxiety and depression, social media channels, and receiving the CABG therapy were associated with lower EQ-VAS index (all P<0.05). Conclusion: Over half of the patients with CHD in China have a low quality of life, which is related to gender, age, obesity, treatment pathway, the presence or absence of comorbidity (ies), and psychological state. In addition to managing the adverse effects of traditional socio-demographic factors on the quality of life, clinical practices should pay attention to the psychological state of patients. Moreover, establishing a WeChat group for doctor-patient communication could improve the quality of life of CHD patients.

[Epidural photobiomodulation accelerates the drainage of brain interstitial fluid and its mechanism].

OBJECTIVE: To evaluate the effect of photobiomodulation (PBM) on the drainage of brain interstitial fluid (ISF) and to investigate the possible mechanism of the positive effect of PBM on Alzheimer's disease (AD). METHODS: Twenty-four SD male rats were randomly divided into PBM group (n=12), sham PBM group (n=6), and negative control group (n=6). According to the injection site of tracer, the PBM group was further divided into PBM-ipsilateral traced group (n=6) and PBM-contralateral traced group (n=6). Rats in the PBM group and the sham PBM group were exposed to the dura minimally invasively on the skull corresponding to the frontal cortical area reached by ISF drainage from caudate nucleus region. The PBM group was irradiated by using 630 nm red light (5-6 mW/cm2), following an irradiation of 5 min with a 2 min pause, and a total of 5 times; the sham PBM group was kept in the same position for the same time using the light without power. The negative control group was kept without any measure. After PBM, tracer was injected into caudate nucleus of each group. The changes of ISF drainage in caudate nucleus were observed according to the diffusion and distribution of tracer molecule by tracer-based magnetic resonance imaging, and the structural changes of brain extracellular space (ECS) were analyzed by diffusion rate in ECS-mapping (DECS-mapping) technique. Finally, parameters reflecting the structure of brain ECS and the drainage of ISF were obtained: volume fraction (α), tortuo-sity (λ), half-life (T1/2), and DECS. The differences of parameters among different groups were compared to analyze the effect of PBM on brain ECS and ISF. One-Way ANOVA post hoc tests and independent sample t test were used for statistical analysis. RESULTS: The parameters including T1/2, DECS, and λ were significantly different among the PBM-ipsilateral traced group, the PBM-contralateral traced group, and the sham PBM group (F=79.286, P < 0.001; F=13.458, P < 0.001; F=10.948, P=0.001), while there was no difference in the parameter α of brain ECS among the three groups (F=1.217, P=0.324). Compared with the sham PBM group and the PBM-contralateral traced group, the PBM-ipsilateral traced group had a significant decrease in the parameter T1/2 [(45.45±6.76) min vs. (76.01±3.44) min, P < 0.001; (45.45±6.76) min vs. (78.07±4.27) min, P < 0.001], representing a significant acceleration of ISF drainage; the PBM-ipsilateral traced group had a significant increase in the parameter DECS [(4.51±0.77)×10-4 mm2/s vs. (3.15±0.44)×10-4 mm2/s, P < 0.001; (4.51±0.77)×10-4 mm2/s vs. (3.01±0.38)×10-4 mm2/s, P < 0.001], representing a significantly increased molecular diffusion rate of in the brain ECS; the PBM-ipsilateral traced group had a significant decrease in the parameter λ (1.51±0.21 vs. 1.85±0.12, P=0.001; 1.51±0.21 vs. 1.89±0.11, P=0.001), representing a significant decrease in the degree of tortuosity in the brain ECS. CONCLUSION: PBM can regulate the brain ISF drainage actively, which may be one of the potential mechanisms of the effect of PBM therapy on AD. This study provides a new method for enhancing the brain function via ECS pathway.

[The clinical value of terminal branches portal vein embolization for hepatocellular carcinoma with insufficient future liver remnant].

Objectives: To examine the efficacy of terminal branches portal vein embolization(TBPVE) for the increment of FLR in hepatocellular carcinoma (HCC) patients and to introduce its clinical value with transcatheter chemoembolization(TACE) in the treatment of HCC patients without surgery. Methods: One hundred and fifty HCC patients from three clinical centers of china underwent TBPVE technique from December 2016 to May 2021,including 89 males and 61 females. The average age was 51.9 years(range:18 to 79 years).One hundred and one patients were diagnosed with a background of HBV infection,including 27 patients with portal venous hypertension.TACE was performed simultaneously with TBPVE in 102 patients.Fifty-three patients underwent hepatectomy,who were subdivided into HBV positive and HBV negative groups,with TACE and without TACE groups to analyze the increment of future liver remnant (FLR), complications and survival data.These data were also analyzed in other 97 patients without hepatectomy. Results: All the patients reached adequate FLR successfully in 14 days after TBPVE including patients with portal venous hypertension.The average increment rates of FLR was 56.2% in 7 days and 57.8% in 14 days after TBPVE. There was no significant difference neither between HBV positive and HBV negative groups(7 days:(55.0±27.3)% vs.(57.8±20.9)%,t=0.885,P=0.373; 14 days:(57.3±24.6)% vs.(58.3±23.7)%;t=0.801,P=0.447),or between with TACE and without TACE groups(7 days:(62.3±26.3)% vs. (48.8±20.6)%;t=1.788,P=0.077;14 days:(64.4±25.0)% vs.(55.2±23.1)%;t=1.097,P=0.257).The morbidity and mortality rates were 20.8% and 1.9% in patients with hepatectomy.The 1-,3-year overall survival(OS) and disease-free(DFS) rates were 87.5%,64.5% and 64.7%,40.6% for patients underwent surgery.There was no significant difference of 1-,3-year OS and DFS between HBV positive and negative groups,but there were different between TACE and without TACE groups.The 1-,3-year OS for patients underwent TBPVE and TACE but without surgery were 80.1%, 53.7%. Conclusion: TBPVE is a good alternative technique for modulation of FLR for staged hepatectomy even in HBV positive HCC patients and can be applied with TACE procedure simultaneously as an option treatment for patients with no intend to surgery.

[Clinical analysis of 9 cases of a novel stent assisted intestinal bypass for preventing anastomotic leakage in laparoscopic assisted radical resection of rectal cancer].

Objective: To examine the safety and effectiveness of a novel stent assisted intestinal bypass for preventing anastomotic leakage in laparoscopic assisted radical resection of rectal cancer. Methods: The clinical data of 9 patients with rectal cancer who underwent laparoscopic radical resection and stent assisted intestinal bypass from September 2019 to June 2020 at the Department of Anus & Intestine Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University were retrospectively analyzed. There were 6 males and 3 females, aged (62.1±6.8) years (range: 53 to 75 years), underwent laparoscopic assisted radical resection of rectal cancer and stent assisted intestinal bypass. A degradable diverting stent was placed at the end of the ileum, and a drainage tube was placed at the proximal end of the stent to bypass the intestinal contents. After operation, the patients were given a diet with less residue. From the 14th day after operation, abdomen X-ray films were taken every 5 to 7 days to observe the destination of the stent dynamically. When the stent was observed to be disintegrated into pieces, the drainage tube was clamped for 3 days to observe any side effects before the tube was removed. The operation time, the time of removing the bypass tube and the total hospital stay were recorded. Results: Laparoscopic assisted radical resection of rectal cancer and stent assisted intestinal bypass were successfully performed in all patients. The operation time was (230.4±48.0) minutes (range: 150 to 318 minutes), and the time of removing shunt tube was (28.8±4.6) days (range: 22 to 34 days). The duration of hospitalization was (21.0±8.6) days (range: 9 to 34 days). Postoperative pathological examination showed 7 cases of moderately differentiated adenocarcinoma, 1 case of moderately well differentiated adenocarcinoma and 1 case of mucinous adenocarcinoma. There were 2 cases of T1, 4 cases of T2 and 3 cases of T3. The number of lymph node dissection was 13.4±3.5 (range: 6 to 18), 3 cases were positive and 6 cases were negative. The post-operation follow-up time was 6 to 16 months, no anastomotic leakage or stenosis was found. Conclusion: Stent assisted intestinal bypass for the prevention of anastomotic leakage in laparoscopic assisted radical resection of rectal cancer is safe and feasible, and shows good short-term effect.

[Current status and controversy of laparoscopic technique in the diagnosis and treatment of gallbladder cancer].

This article introduces the current status and controversy of laparoscopic technique in the treatment of gallbladder carcinoma. Combined with the characteristics of incidental gallbladder carcinoma, the feasibility of laparoscopic techniques for the treatment of early gallbladder carcinoma is analyzed.In the era of minimally invasive medical, laparoscopic techniques should play a more important role in the management of gallbladder cancer, but the long-term prognosis of laparoscopic radical surgery for gallbladder cancer needs strict prospective and high-volume clinical research to validate.

[Current status and prospect of surgical treatment of liver cancer].

With the rapid development of liver surgery,minimally invasive techniques have been widely used in liver surgery. Many challenging liver can be performed laparoscopically to decrease the surgical trauma. At the same time,the efficiency and accuracy of liver surgeries have been highly improved by the advanced assisted technology of liver surgery. The purpose of this article is to summarize the current situation of liver surgery as well as the future of liver surgery.

[Severe acute pancreatitis with iatrogenic duodenal fistula: cause and minimal invasive treatment].

Objective: To investigate the causes and treatment of severe acute pancreatitis (SAP) with iatrogenic duodenal fistula. Methods: The clinical data of the SAP patients with duodenal fistula treated in the Severe Acute Pancreatitis Center of Sir Run Run Shaw Hospital from May 2015 to May 2018 was analyzed retrospectively. Results: A total of 11 patients were enrolled, among which 5 cases of duodenal fistula were caused by iatrogenic injury, including 2 cases of puncture injury, 2 cases of nutritional tube injury and 1 case of drainage tube injury. For patients with poor infection control after conservative treatment, laparoscopic assisted debridement through the right retroperitoneal approach was performed. Treatment of two patients failed for liver failure and the remaining patients were cured. Conclusions: Iatrogenic injury is one of the causes of duodenal fistula in patients with severe pancreatitis. Laparoscopic assisted debridement through the right retroperitoneal approach is an effective treatment for duodenal fistula.

[The new classifications of biliary tract diseases based on actual anatomy].

In order to facilitate the treatment strategies for biliary tract injury, hilar cholangiocarcinoma, bile duct tumor thrombus, cholangiocellular carcinoma and bile duct cystic dilatation, many classifications have been made, even more than 10 types for one disease. Each type is represented by numbers or English alphabet, which are not only confusing but also difficult to remember. The Academician Mengchao Wu divided the liver into five sections and four segments base on its anatomy, this classification is very direct and visual, thus had been using till now. In order to overcome those complicated problems, it is considered to develop a new classification based on actual anatomic location similar to that for liver cancer, which is easy to remember and to directly determine the treatment strategy. All kinds of classifications have their own characteristics and advantages and disadvantages. This practical classifications avoid the complexity and may be useful for clinicians.

[The research on the application of uncut Roux-en-Y esophagojejunostomy in the digestive reconstruction after totally laparoscopic total gastrectomy].

Objective: To evaluate the safety and flexibility of uncut Roux-en-Y esophagojejunostomy in totally laparoscopic total gastrectomy (TLTG). Methods: Between July 2016 to November 2016, 15 patients received totally laparoscopic total gastrectomy plus uncut Roux-en-Y esophagojejunostomy in the Sir Run Run Shaw hospital. Clinical data of those patients, including operative indexes, post-operative indexes and fellow-up data, were analyzed respectively. Results: A total of 15 patients were enrolled in this study, ten were corpus carcinoma and five were esophagogastric junction carcinoma. The total operative time and anastomosis time was (25.0±4.3) min and (25.0±4.3) min, the blood loss during operation was (133.3±121.2) ml. All the operations were performed successfully, and no one was transferred to open surgery. All the patients were encouraged to off-bed activity at first day after surgery. The first time to flatus, the first time to liquid food intake and the length of stay in hospital were (4.1±0.8) days, (5.1±0.9) days and (9.3±1.6) days, respectively. The pathological staging of these patients was stage Ⅰb in 1 case, stage Ⅱa in 3 cases, stageⅡb in 2 cases, stage Ⅲb in 3 cases, stage Ⅲc in 6 cases. The lymph node harvest was (36.0±12.3). Cutting margins in all patients were negative. Pulmonary infection occurred in one patient postoperatively and recovered after antibiotic treatment. No death and severe complication was found. Liver metastasis occurred in one patient eight months after operation. One patient was found recurrence in anastomotic site. No Roux-en-Y stasis syndrome was found. Conclusions: Uncut Roux-en-Y esophagojejunostomy in TLTG is safe and flexible.

[Retroperitoneal laparoscopic debridement therapy for infected severe acute pancreatitis].

Objective: To investigate the feasibility and availability of retroperitoneal laparoscopic debridement therapy for patients with infected severe acute pancreatitis. Methods: Clinical data of 6 patients with severe acute pancreatitis who underwent retroperitoneal laparoscopic necrotic tissue debridement therapy in the Severe Acute Pancreatitis Center of Sir Run Run Hospital between August 2014 and October 2015 was retrospectively analyzed. The laparoscopic instruments and sponge forceps were used to remove necrotic tissue under retroperitoneal space, and double-cavity drainage tube was left for continuous washing. The perioperative indicators were collected and analyzed. Results: Two of six patients underwent two surgeries, and the others underwent one surgery, with an average operation time of (220.0±58.3) minutes and a mean hospital stay time of 62.6 days (35-117 days). One patient underwent re-operation after 33 days because of intraperitoneal hemorrhage, and another patient suffered pancreatic pseudocyst after the surgery, but no one died in hospital. Conclusion: Retroperitoneal laparoscopic debridement therapy is an additional choice for patients with infected severe acute pancreatitis, especially for those who had limited necrosis under retroperitoneal space. Furthermore, the therapy is in line with the concept of minimally invasive surgery and enhanced recovery after surgery.

[Clinical effect of terminal branches portal vein embolization combined with transcatheter arterial chemoembolization on liver neoplasms].

Objective: To analyze the efficacy of branches portal vein embolization (TBPVE) combined with transcatheter arterial chemoembolization (TACE) on liver neoplasms. Methods: From August 2016 to May 2017, there were 13 patients including 11 males and 2 females with primary hepatocellular carcinoma who underwent TBPVE+ TACE , among whom there were 11 cases with a history of HBV infection.Average age of the 13 patients was (60.8±6.2)years. The live function of all patients were Child-Pugh A classification.The CT or MRI images of each patient was reconstructed and the standard liver volume(SLV) before TBPVE+ TACE was (1 181.2±49.3)ml, estimated future liver remnant(FLR) was (326.1±72.1)ml and FLR/SLV was (27.6±6.0)%.The puncture site for TBPVE was determined by the three-dimensional reconstruction of portal vein.CT scan or MRI, AFP and liver function test were repeated after one and two weeks after TBPVE+ TACE.FLR and FLR/SLV were calculated respectively.Hepatectomy would be performed if the patients agreed.The postoperative complications were analyzed. Results: On the 7thday after TBPVE+ TACE, the FLR/SLV was(42.6±8.0)% and the FLR increasement was(56.0±24.6)%.The level of AFP decreased from(87.9±81.8)µg/L to (29.7±20.9)µg/L.On the 14thday after TBPVE+ TACE, the FLR/SLV was(45.8±6.2)% and the FLR increasement was(71.8±29.0)%.Four patients underwent surgery which including 2 right hepatectomies and 2 right trisegmentectomies in 2 weeks after TBPVE+ TACE.Nine patients were performed with targeting intratumoral lactic acidosis TACE (TILA-TACE). No severe complication occurred in all patients. Conclusions: TBPVE could induce a rapid growth of the liver remnant but still with the concern of inducing the growth of neoplasms at the same time.To combine TACE in TBPVE therapy not also can the growth of neoplasms be prevented but also inducing its shrinking.This method might be a new mode for the treatment of hepatocellular carcinoma.

[Application of laparoscopic transection of median hepatic fissure in difficult laparoscopic liver resections].

Objective: The aim was to explore the strategy and clinical value of laparoscopic transection of median hepatic fissure (MHF) in difficult laparoscopic liver resections. Methods: First the MHF was located and marked, then the transection plane of the MHF was set. Next, the laparoscopic Multifuctional Operative Dissector (LPMOD) and the technique of curettage and aspiration were utilized to transect the liver beginning from the middle portion of the gallbladder fossa, in a caudal-to-cranial and anterior-to-posterior direction, until the clear exposure of the anterior surface of the intrahepatic inferior vena cava. Transection of the MHF was accurately achieved. Finally, dissection of the second and third porta hepatis were carefully performed and mobilization of the transected liver was achieved. This technique of laparoscopic transection of MHF was successfully performed in 13 patients in difficult laparoscopic liver resections. Results: Between April 2014 and August 2015, 13 patients received the technique of laparoscopic transection of MHF in difficult laparoscopic liver resections, including 10 cases of laparoscopic right hepatectomy, two cases of laparoscopic left hepatectomy and one case of associating liver partition and portal vein ligation for staged hepatectomy (ALPPS). The maximum size of the transected tumor was 15 centimeter. Duration of surgery was 240-430 min[Mean, 324.4±50.0]; the time for transection of the MHF was 40-118 min[mean, 66.4±22.7]. Blood loss was 200-2 000 ml[583.3±452.9]. The length of postoperative hospital stay was 6-25 days[mean, 13.2±5.2]. Seven patients received intraoperative transfusions. No postoperative intraabdominal bleeding, liver failure or other severe postoperative complications occurred. No perioperative death occurred. Conclusions: Application of laparoscopic transection of the MHF in difficult laparoscopic liver resections can help to clearly expose the second and third porta hepatis, especially in patients who have huge tumors and poor exposure for hepatic dissection. Moreover, precise location and transection of the MHF remains very important strategies of applying this technique.

[Terminal branches portal vein embolization for planed hepatectomy].

OBJECTIVE: To explore the application of the technique of terminal branches portal vein embolization(TBPVE)for planed hepatectomy. METHODS: From February 2016 to June 2016, 4 patients with hepatocellular carcinoma underwent TBPVE and liver resection in Yuebei People's Hospital (n=3) and Jiangxi Ji'an Central People's Hospital (n=1). All of them were male and were 50, 64, 39 and 47 years old respectively. All the tumors located in the right lobe. All patients had the liver function of Child-Pugh A classification and liver cirrhosis level of G2S4. The standard liver volume (SLV) were 1 291, 1 109, 1 177 and 1 242 ml and estimated future liver remnant(FLR) were 315, 347, 306 and 323 ml respectively. The puncture site of TBPVE was determined by the three-dimensional reconstruction of portal vein. Three patients were punctured in the segment Ⅵ and the other one punctured in the segment Ⅲ. CT scan was repeated 2 weeks after TBPVE and FLR and FLR/SLV were calculated. All patients underwent right hepatectomy 2 weeks after TBPVE. RESULTS: On the 14(th) day after TBPVE, the FLR of 4 patients were 529, 462, 469 and 498 ml which increased 67.9%, 33.1%, 53.3% and 54.2% compared with that before TBPVE, and FLR/SLV were 41.0%, 41.7%, 39.8% and 40.1% respectively. No severe complication occurred. Right hepatectomy were performed 2 weeks after TBPVE. No inflow blood control applied during the liver resection. The mean blood loss was 950 ml and the mean operating time was 3.3 hours (ranging from 3 to 4 hours). One patient had respiratory infection and two had slight jaundice and ascites for a short period. No other complication occurred. CONCLUSION: The TBPVE could induce a rapid and large FLR volume that give chances to patients with small FLR to have liver resection for hepatocellular carcinoma.

Investigating the ability of nanoparticle-loaded hydroxypropyl methylcellulose and xanthan gum gels to enhance drug penetration into the skin.

Nanoparticle-loaded topical formulations can disrupt drug aggregation through controlled drug-nanoparticle interactions to enhance topical drug delivery. However, the complex relationship between the drug, nanoparticle and formulation vehicle requires further understanding. The aim of this study was to use nanoparticle-loaded hydroxypropyl methylcellulose (HPMC) and xanthan gum gels to probe how the drug, nanoparticle and formulation vehicle interactions influenced the delivery of an aggregated drug into the skin. Tetracaine was chosen as a model drug. It was loaded into HPMC and xanthan gum gels, and it was presented to porcine skin using infinite and finite dosing protocols. Gel infinite doses showed no important differences in tetracaine skin permeation rate, but HPMC gel finite doses delivered the drug more efficiently (46.99±7.96µg/cm2/h) compared to the xanthan gum (1.16±0.14µg/cm2/h). Finite doses of the nanoparticle-loaded HPMC gel generated a 10-fold increase in drug flux (109.95±28.63µg/cm2/h) compared to the equivalent xanthan gum system (14.19±2.27µg/cm2/h). Rheology measurements suggested that the differences in the gels ability to administer the drug into the skin were not a consequence of gel-nanoparticle interactions rather, they were a consequence of the dehydration mediated diffusional restriction imparted on the drug by xanthan gum compared to the viscosity independent interactions of HPMC with the drug.