Multivariate analysis of alveolar bone dehiscence and fenestration in anterior teeth after orthodontic treatment: A retrospective study.

OBJECTIVE: To compare the prevalence of fenestration and dehiscence between pre- and post-orthodontic treatment and to explore the factors related to fenestration and dehiscence in the anterior teeth after treatment. METHODS: This study included 1000 cone-beam computed tomography (CBCT) scans of 500 patients before (T1) and after (T2) orthodontic treatment. These images were imported into Dolphin 11.9 software to detect alveolar fenestration and dehiscence in the anterior teeth area. The chi-square test and Fisher's exact test were performed to compare the prevalence of alveolar bone defects between time points T1 and T2. A total of 499 patients were selected for logistic regression analysis to examine the correlation among age, sex, crowding, sagittal facial type, extraction, miniscrew use and fenestration or dehiscence post-treatment. RESULTS: Except for the maxillary lingual fenestration and labial fenestration of mandibular canines, a significant change in the prevalence of fenestration and dehiscence was noted between time points T1 and T2 (P < .025). Multinomial logistic regression showed that age, miniscrew use and extraction highly influenced the prevalence of anterior lingual dehiscence (P < .05). Dehiscence of the mandibular labial side (skeletal Class III vs. I, OR = 2.368, P = .000) and fenestration of the mandibular lingual side (skeletal Class II vs. I, OR = 2.344, P = .044) were strongly correlated with the sagittal facial type. Dehiscence of the maxillary labial side (moderate vs. mild, OR = 1.468, P = .017) was significantly associated with crowding. CONCLUSIONS: Older age, maxillary moderate crowding, skeletal Class III, extraction and miniscrew potentially significantly affect the prevalence of anterior teeth dehiscence. Adult females, skeletal Class III patients on the mandibular labial side and skeletal Class II patients on the mandibular lingual side should be monitored for anterior teeth fenestration.

The short- and long-term effects of congenital occlusion loss of the unilateral first permanent molar on the temporomandibular joint morphology and position: A retrospective study based on cone-beam computed tomography.

OBJECTIVE: To investigate the effects of congenital unilateral first permanent molar occlusal loss (CUMOL) on the morphology and position of temporomandibular joint (TMJ). MATERIALS AND METHODS: Cone-beam computed tomography (CBCT) images of 37 patients with CUMOL (18 males and 19 females, mean age: 13.60 ± 4.38 years) were divided into two subgroups according to the status of second molar (G1: the second molar not erupted, n = 18, G2: second molar erupted, n = 19). The control group consisted of 33 normal occlusion patients (9 males and 24 females, mean age: 16.15 ± 5.44 years) and was divided into 2 subgroups accordingly (G3: the second molar had not erupted, n = 18, G4: the second molar had erupted and made contact with the opposing tooth, n = 15). Linear and angular measurements were used to determine the characteristics of TMJ. RESULTS: In G1, the condyle on the side of the CUMOL shifts posteriorly, with significant side differences observed in Anterior space (AS, P < .05) and Posterior space (PS, P < .05). However, with the eruption of the second permanent molars, in G2, the condyle on the CUMOL side moves posteriorly and inferiorly. This results in significant lateral differences in the AS (P < .05), PS (P < .05), and Superior space (SS, P < .05). Additionally, there is an increase in the thickness of the roof of the glenoid fossa (TRF) on the CUMOL side (P < .05), and a decrease in the inclination of the bilateral articular eminences (P < .05). CONCLUSIONS: CUMOL can affect the position and the morphology of the condyle and was associated with the eruption of the second permanent molars. Before the eruption of the second permanent molars, CUMOL primarily affects the position of the condyle. After the emergence of the second permanent molars, CUMOL leads to changes in both the condyle's position and the morphology of the glenoid fossa.

Mechanical loading and autophagy: A study on the BoNT-A injection-induced condylar cartilage degeneration.

Botulinum toxin A (BoNT-A) has emerged as a treatment option for temporomandibular disorder (TMD). By injecting BoNT-A into the masseter muscle, it is possible to reduce mechanical loading on the temporomandibular joint (TMJ). However, numerous prior studies have indicated excessive reduction in mechanical loading can have detrimental effects on TMJ cartilage. This study proposes that autophagy, a process influenced by mechanical loading, could play a role in BoNT-A-induced mandibular condyle cartilage degeneration. To explore this hypothesis, we employed both BoNT-A injection and an excessive biting model to induce variations in mechanical loading on the condyle cartilage of C57BL/6 mice, thereby simulating an increase and decrease in mechanical loading, respectively. Results showed a significant reduction in cartilage thickness and downregulation of Runt-related transcription factor 2 (Runx2) expression in chondrocytes following BoNT-A injection. In vitro experiments demonstrated that the reduction of Runx2 expression in chondrocytes is associated with autophagy, possibly dependent on decreased YAP expression induced by low mechanical loading. This study reveals the potential involvement of the YAP/LC3/Runx2 signaling pathway in BoNT-A mediated mandibular condylar cartilage degeneration.

Comprehensive positional and morphological assessments of the temporomandibular joint in adolescents with skeletal Class III malocclusion: a retrospective CBCT study.

BACKGROUND: Condyle-fossa relationships in adolescents with skeletal Class III malocclusion remain unclear. Therefore, this study used cone-beam computed tomography (CBCT) to evaluate the position and morphology of the temporomandibular joint (TMJ) in adolescents with skeletal Class III malocclusion. METHODS: In this cross-sectional retrospective study, CBCT images from 90 adolescents with skeletal Class III malocclusion and 30 controls were analysed. Adolescents with skeletal Class III malocclusion were divided into different groups based on (1) sex (male and female), (2) sides (right and left), (3) age (early, middle, and late adolescence), and (4) vertical skeletal patterns (hyperdivergent, normodivergent, and hypodivergent). Morphology of the condyle and fossa as well as condylar position, was compared among groups. Data were collected and submitted for statistical analysis. This study adheres to STROBE guidelines. RESULTS: Regarding the intergroup comparisons, there were significant differences in TMJ position and morphology between the skeletal Class III malocclusion with different vertical skeletal patterns and control groups (P < 0.05). Within groups, condyle-fossa relationships differed significantly according to sex, age, and vertical skeletal patterns (P < 0.05); however, the mean values were not statistically different between left and right sides in adolescents with skeletal Class III malocclusion. CONCLUSIONS: Our findings can be used clinically and radiographically to evaluate the condyle and glenoid fossa features in adolescents with skeletal Class III malocclusion, providing a basis for better TMD diagnosis and orthodontic treatment.

Long-term changes in the anterior alveolar bone after orthodontic treatment with premolar extraction: A retrospective study.

OBJECTIVES: To evaluate the morphometric changes in maxillary and mandibular anterior alveolar bone after orthodontic treatment and retention for 18-24 months by cone-beam computed tomography (CBCT). SETTING AND SAMPLE POPULATION: Thirty-four adolescent patients (12 males and 22 females; mean age: 14.29 ± 1.24 years) diagnosed with bimaxillary dentoalveolar protrusion and with extractions of the 4 first premolars were included. MATERIALS AND METHODS: The labial and lingual (palatal) alveolar bone thickness, height and root length of the maxillary and mandibular anterior teeth were assessed using CBCT imaging at the pre-treatment (T1), post-treatment (T2) and retention phases (T3). Voxel-based superimpositions of the T2 and T3 images were performed, and the distances of incisal and apical movement between T2 and T3 were measured to determine whether relapses occurred. RESULTS: After orthodontic treatment, the labial and lingual (palatal) bone height decreased significantly (P < .05) and the labial thickness at the crestal (L1), midroot (L2), and apical levels (L3) had no significant change, while the lingual (palatal) bone thickness at all three levels decreased significantly (P < .05). After 18-24 months of retention, the lingual (palatal) height and the lingual (palatal) thickness at the crestal (L1) level increased significantly (P < .05). There were no obvious incisal and apical movements of the anterior teeth between T2 and T3 (P > .05), indicating that no relapses occurred. CONCLUSIONS: Even though lingual (palatal) alveolar loss occurred due to the orthodontic treatment, the cervical alveolar bone seemed to recover over time. Therefore, appropriate camouflage treatment can be used in patients with bimaxillary dentoalveolar protrusion, and this treatment will not irreversibly deteriorate periodontal health and affect the orthodontic treatment stability.

Age-related variations in position and morphology of the temporomandibular joint in individuals with anterior openbite and crossbite: a multi-cross-sectional comparative study.

BACKGROUND: This study aimed to compare the age-related positional and morphological characteristics of the temporomandibular joint (TMJ) between individuals with anterior openbite or crossbite and controls. METHODS: This multi-cross-sectional comparative study analysed cone-beam computed tomography images of 750 participants, equally divided into the openbite, crossbite, and control groups (OBG, CBG, and CG, respectively). Each group was further divided into five subgroups (8-11 years, 12-15 years, 16-19 years, 20-24 years, and 25-30 years). Measurements of the TMJ included the position of the condyles in their respective fossae and morphology of the condyles and fossae. Data were submitted to statistical analysis. The study adhered to the STROBE Statement checklist for reporting of cross-sectional studies. RESULTS: Condyles were positioned more posteriorly with increasing age in all groups, and the condylar position was more posterior in the OBG than in the CBG. The articular eminence inclination increased with age in all the groups. There were significant differences in the articular eminence inclination among the three major groups at the age of > 15 years, and the condylar path was flatter in the CBG than in the OBG. CONCLUSIONS: Age-related morphological and positional characteristics of the TMJ differed considerably among OBG, CBG and CG. Contrary to CBG, OBG was found to have relatively posterior condylar position and steeper condylar path.

Retracted: Dynamic Evaluation of Orthodontically-Induced Tooth Movement, Root Resorption, and Alveolar Bone Remodeling in Rats by in Vivo Micro-Computed Tomography.

This publication has been retracted by the Editor due to the identification of non-original figure images and manuscript content that raise concerns regarding the credibility and originality of the study and the manuscript. Reference: Jianping Zhou, Fengxue Yang, Xiaolin Xu, Gang Feng, Jun Chen, Jinglin Song, Hongwei Dai. Dynamic Evaluation of Orthodontically-Induced Tooth Movement, Root Resorption, and Alveolar Bone Remodeling in Rats by in Vivo Micro-Computed Tomography. Med Sci Monit, 2018; 24: 8306-8314. DOI: 10.12659/MSM.912470.

The relation between incisal guidance angle and the growth and development of temporomandibular joint: a multi-cross-sectional retrospective study.

BACKGROUND: The incisal guidance angle (IGA) is related to temporomandibular joint (TMJ), and changes to the IGA are often involved in the prosthetic and orthodontic treatment of anterior teeth. However, the influence of incisal guidance on the growth, development and remodelling of the TMJ is not yet clear. The aim of this study was to investigate age-related morphological differences in the TMJ in subjects with different IGAs. METHODS: Cone-beam computed tomography (CBCT) images of 274 patients were included (group 1, IGA < 45°; group 2, 45° ≤ IGA ≤ 60°; group 3, IGA > 60°). Each group was then divided into 4 age groups (group a, 6-12 years; group b, 13-16 years; group c, 17-25 years; group d, 26-33 years). TMJ morphology was assessed by linear measurements, angular measurements, and subjective evaluations. The IGA and occlusal plane angle were also measured. RESULTS: Anterior inclination of condyle (AIC) increased with age in the three IGA groups but decreased from 17 years onward in group 2 (P < 0.05). In the age groups analysis, the AIC in group 1 was smaller than that in group 3 but larger than that in group 2 (P > 0.05). Articular eminence inclination (AEI) decreased with age in group 1 (P = 0.027) but increased with age in group 3 (P = 0.053). The AEI in group 2 was larger than that in group 1 at 17-25 years (P = 0.046), and it was larger in group 3 than in group 1 at 26-33 years (P = 0.047). The IGA had a weak correlation with AEI (P < 0.05). CONCLUSION: The articular fossa of patients with shallower incisal guidance changed to a flatter shape with age, whereas the condylar anterior slope and articular eminence of patients with steeper incisal guidance changed towards a steeper alignment. There was a correlation between IGA and TMJ shape.

Soft tissue facial changes among adult females during alignment stage of orthodontic treatment: a 3D geometric morphometric study.

BACKGROUND: To investigate changes in facial morphology during the first six months of orthodontic treatment among adult females receiving orthodontic treatment. METHODS: 43 adult females receiving orthodontic treatment were randomly recruited. 3D facial images were taken at baseline (T0), three months (T1), and six months (T2) after treatment initiation. Spatially dense facial landmarks were digitized to allow for sufficient details in characterization of facial features. 3D geometric morphometrics and multivariate statistics were used to investigate changes in mean and variance of facial shape and facial form associated with treatment. RESULTS: We observed statistically significant changes in facial shape across the three treatment stages (p = 0.0022). Pairwise comparisons suggested significant changes from T0 to T1 (p = 0.0045) and from T0 to T2 (p = 0.0072). Heatmap visualization indicated that the buccal and temporal region were invaginated while the labial region became protruded with treatment. The magnitude of shape change was 0.009, 0.004, and 0.010 from T0 to T1, T1 to T2, and T0 to T2, respectively, in unit of Procrustes distance. The average magnitude of change per-landmark was 1.32 mm, 0.21 mm, and 1.34 mm, respectively. Changes in mean facial form were not statistically significant (p = 0.1143). No changes in variance of facial shape were observed across treatment stages (p > 0.05). CONCLUSION: Rate of facial changes was twice as fast during the first three months as that during fourth to sixth month. Buccal and temporal region became invaginated while labial region became protruded with treatment.

Dynamic Evaluation of Orthodontically-Induced Tooth Movement, Root Resorption, and Alveolar Bone Remodeling in Rats by in Vivo Micro-Computed Tomography.

BACKGROUND The aim of this study was to dynamically evaluate tooth movement, root resorption, and remodeling of alveolar bone using different forces to cause tooth movement in rats. MATERIAL AND METHODS 12-week-old male Sprague-Dawley rats were selected. Nickel-titanium (Ni-Ti) coil springs (20 g, 50 g, and 100 g forces) were placed for mesial movement of the left first maxillary molar teeth. Tooth movement, root resorption, and microarchitectural parameters of the trabecular bone were evaluated by in vivo micro-CT. Histological examination was used to observe the root resorption, alveolar bone remodeling, and changes in osteoclasts from day 0 to day 14. RESULTS The tooth movement distance increased significantly over the initial 3 days in the 3 groups. The 20 g force group showed more tooth movement than in the 50 and 100 g force groups after 14 days (P<0.05). From days 7 to 10, root resorption lacunae appeared in the 3 groups and then stabilized, and the 100 g force group produced more lacunar resorption than in the anther 2 groups (P<0.05). Compared to day 0, the trabecular thickness and bone volume fraction on the pressure side gradually decreased from day 7 to day 14. The structure model index increased significantly from day 3 to day 14. Histological examination showed remarkable root resorption craters and osteoclasts positive for tartrate-resistant acid phosphatase in the root resorption lacunae in the 50 g and 100 g groups from day 7 to day 14. CONCLUSIONS A 100 g heavy force can be used to establish a root resorption model in rats.

Tyroservatide-TPGS-paclitaxel liposomes: Tyroservatide as a targeting ligand for improving breast cancer treatment.

Tyroservatide (YSV) is a tripeptide that has been approved for clinical testing, as a new anticancer drug. In the current study, YSV-stearic acid (YSV-SA) was inserted into the surface of d-alpha-tocopheryl polyethylene glycol 1000 succinate monoester (TPGS)-modified paclitaxel (PTX) liposomes (TP-Lip) to form YSV-conjugated TP-Lip (TYP-Lip). Both in vivo imaging and in vitro cell uptake analysis indicated that these modifications could increase tumor-targeting and cell uptake of the liposomes. Optimal antitumor effects were achieved via tail vein injections of TYP-Lip in MB-231 tumor-bearing nude mice. Overall, the formed TYP-Lip not only achieved a synergistic anticancer effect through YSV and PTX, but also improved tumor-targeting and exhibited further antitumor capabilities. These results indicated that combining biological (YSV) and chemotherapeutic (PTX) agents is an efficient combinatorial delivery strategy for enhanced tumor targeting and synergistic antitumor effects.

Somatostatin Receptor-Mediated Tumor-Targeting Nanocarriers Based on Octreotide-PEG Conjugated Nanographene Oxide for Combined Chemo and Photothermal Therapy.

Nano-sized in vivo active targeting drug delivery systems have been developed to a high anti-tumor efficacy strategy against certain cancer-cells-specific. Graphene based nanocarriers with unique physical and chemical properties have shown significant potentials in this aspect. Here, octreotide (OCT), an efficient biotarget molecule, is conjugated to PEGylated nanographene oxide (NGO) drug carriers for the first time. The obtained NGO-PEG-OCT complex shows low toxicity and excellent stability in vivo and is able to achieve somatostatin receptor-mediated tumor-specific targeting delivery. Owing to the high loading efficiency and accurate targeting delivery of anti-cancer drug doxorubicin (DOX), our DOX loaded NGO-PEG-OCT complex offers a remarkably improved cancer-cell-specific cellular uptake, chemo-cytotoxicity, and decreased systemic toxicity compared to free DOX or NGO-PEG. More importantly, due to its strong near-infrared absorption, the NGO-PEG-OCT complex further enhances efficient photothermal ablation of tumors, delivering combined chemo and photothermal therapeutic effect against cancer cells.

Redox-Sensitive Micelles Based on O,N-Hydroxyethyl Chitosan-Octylamine Conjugates for Triggered Intracellular Delivery of Paclitaxel.

A redox-sensitive micellar system constructed from an O,N-hydroxyethyl chitosan-octylamine (HECS-ss-OA) conjugate with disulfide linkages between the hydrophobic alkyl chains and hydrophilic chitosan backbone was synthesized for triggered intracellular delivery of hydrophobic paclitaxel (PTX). In aqueous environments, conjugates formed micelles with high PTX loading (>30%). Mechanistically, the sensitivity of HECS-ss-OA micelles to reducing environments was investigated using the parameters of in vitro release and particle size. Intracellular release of nile red fluorescence alongside cytotoxicity studies further confirmed the potency of redox-sensitive micelles for intracellular drug delivery compared with redox-insensitive micelles. Additionally, an in vivo study confirmed the efficacy of PTX-loaded micelles in tumor-bearing mice with superior antitumor efficacy and diminished systemic toxicity when compared with the redox-insensitive micelles and a PTX solution. These results demonstrate the potential of redox-sensitive HECS-ss-OA micelles for intracellular trafficking of lipophilic anticancer drugs.

Well-Defined Redox-Sensitive Polyethene Glycol-Paclitaxel Prodrug Conjugate for Tumor-Specific Delivery of Paclitaxel Using Octreotide for Tumor Targeting.

A redox-sensitive prodrug, octreotide(Phe)-polyethene glycol-disulfide bond-paclitaxel [OCT(Phe)-PEG-ss-PTX], was successfully developed for targeted intracellular delivery of PTX. The formulation emphasizes long-circulation-time polymer-drug conjugates, combined targeting based on EPR and OCT-receptor mediated endocytosis, sharp redox response, and programmed drug release. The nontargeted redox-sensitive prodrug, mPEG-ss-PTX, and the targeted insensitive prodrug, OCT(Phe)-PEG-PTX, were also synthesized as controls. These polymer-PTX conjugates, structurally confirmed by 1H NMR, exhibited approximately 23,000-fold increase in water solubility over parent PTX and possessed drug contents ranging from 11% to 14%. The redox-sensitivity of the objective OCT(Phe)-PEG-ss-PTX prodrug was verified by in vitro PTX release profile in simulated reducing conditions, and the SSTRs-mediated endocytosis was demonstrated by flow cytometry and confocal laser scanning microscopy analyses. Consequently, compared with mPEG-PTX and OCT(Phe)-PEG-PTX, the OCT(Phe)-PEG-ss-PTX exhibited much stronger cyotoxicity and apoptosis-inducing ability against NCI-H446 tumor cells (SSTRs overexpression), whereas a comparable cytotoxicity of these prodrugs was obtained against WI-38 normal cells (no SSTRs expression). Finally, the in vivo studies on NCI-H466 tumor-bearing nude mice demonstrated that the OCT(Phe)-PEG-ss-PTX possessed superior tumor-targeting ability and antitumor activity over mPEG-PTX, OCT(Phe)-PEG-PTX and Taxol, as well as minimal collateral damage. This targeted redox-sensitive polymer-PTX prodrug system is promising in tumor therapy.

Amorphous solid dispersion with increased gastric solubility in tandem with oral disintegrating tablets: a successful approach to improve the bioavailability of atorvastatin.

CONTEXT: Serious efforts have been made to overcome the bioavailability problems of ever increasing number of poorly soluble drugs, including atorvastatin (ATO); however, enhancing its gastric solubility has not received much attention. OBJECTIVES: To improve the bioavailability of ATO by increasing its gastric solubility in a stable oral disintegration tablet (ODT) formulation. MATERIALS AND METHODS: Amorphous solid dispersion (ASD) of ATO with Eudragit® EPO was used as API in ODT formulation. Characterization using Differential scanning calorimetry, Powder X-ray diffraction, Fourier transform infrared drug-polymer interaction simulated by molecular modeling, solubility, dissolution and stability studies together with in vivo evaluation. RESULTS AND DISCUSSION: In ASD there was uniform distribution of drug in the polymer and it retained the amorphous nature without any chemical interactions except the possibility of hydrogen bond formation, with substantially higher gastric solubility. The dissolution profile of the ODT containing ASD was significantly improved >90% within 15 min compared with 25% of plain ATO formulation. In vivo results showed an overall enhancement in the apparent bioavailability (83% and 434% more than Lipitor® and plain amorphous ATO tablets, respectively). Combining the ASD with ODT presents a reliable solution to overcome the low solubility and bioavailability problems of ATO in a simple, robust and cost effective formulation.

Versatile reticular polyethylenimine derivative-mediated targeted drug and gene codelivery for tumor therapy.

The study is aimed to develop a versatile reticular polyethylenimine (PEI) derivative eprosartan-g-PEI (ESP) conjugate-mediated targeted drug and gene codelivery system for tumor therapy. Eprosartan (ES), an angiotensin II type 1 receptor blocker (ARB), which has been proven to exert beneficial effects on tumor progression, vascularization, and metastasis as the conventional antihypertensive drug, was conjugated with PEI-1.8K chains into ESP via a bis-amide bond of pH-sensitivity to overcome high cytotoxicity and nontargeted gene delivery of PEI-25K. P53 gene was encapsulated in the ESP to form the codelivery system of ESP/p53 complexes, and this system was comprehensively characterized. In vitro ESP/p53 complexes had a significant effect on inhibiting angiogenesis by reducing the expression and secretion of VEGF. In vivo the effective antitumor activity of ESP/p53 complexes was observed on nude mice bearing PANC-1 xenografts, and the microvessel density (MVD) examination demonstrated that ESP/p53 complex-produced antitumor efficacy was closely correlated with the efficient angiogenesis repression. These findings disclosed that the multifunctional ESP/p53 complexes might be a promising dual anticancer drug and gene codelivery system.

Ternary complexes with core-shell bilayer for double level targeted gene delivery: in vitro and in vivo evaluation.

PURPOSE: Hyaluronic acid (HA)/polyethyleneimine-dexamethasone (PEI-Dex)/DNA ternary complexes with "core-shell" bilayer were developed for double level targeted gene delivery. A PEI1800-Dex, as a core, was applied to compact DNA into a nano-sized structure and facilitate the nuclear translocation of DNA after endocytosis into tumor cells, and a polyanion HA, as the outer corona, was employed to improve targeted tumor delivery and reduce cytotoxicity. METHODS: PEI-Dex was synthesized and characterized by (1)H NMR. The characterizations of ternary complexes were investigated. Their biological properties, including transfection efficiency, cytotoxicity, cellular uptake and in vivo efficacy were evaluated systemically. RESULTS: Ternary complexes with the size of about 160 nm exhibited the lowest cytotoxicity and the highest transfection efficiency in B16F10 cells among investigated complexes. The sub-cellular localization study confirmed that ternary complexes could facilitate more efficient cell uptake and nuclear transport of DNA than binary complexes. Moreover, Cy7-labeled ternary complexes obviously accumulated in the tumor after i.v. administration, indicating that ternary complexes could assist the DNA targeting to the tumor. In in vivo studies, HA/PEI1800-Dex/DNA ternary complexes showed confirmed anti-inflammation activity, and could significantly suppress tumor growth of tumor-bearing nude mice. CONCLUSIONS: HA/PEI-Dex/DNA ternary complexes might be a promising targeted gene delivery system.

Synthesis, characterization, drug-loading capacity and safety of novel pH-independent amphiphilic amino acid copolymer micelles.

A novel block copolymer containing two polymeric components, poly(L-aspartic acid)-b-poly (L-phenylalanine) (PAA-PPA), was synthesized and its potential for the preparation of copolymer micelles with a poorly water-soluble drug was investigated in this study. The chemical structure and physical properties of PAA-PPA were characterized by FTIR, 1H NMR and TG. The degree of polymerization of PAA-PPA was calculated by analyzing the relative area of N-CH signal and C-CH3 of 1H NMR spectra. The critical micelle concentration (CMC) of the PAA-PPA achieved a minimum of 11.1 mg/L. Studies on the drug-free PAA-PPA solutions showed PAA-PPA aggregation into micellar type in the sub-150 nm size range. Furthermore, the size of the PAA-PPA micelles was found to be pH-independent between the pH range of 4.0 and 8.0, which could be favorable to avoid the limitation of the size change at the specified pH value seeking drug stability. 4-amino-2-trifluoromethyl-phenyl retinate (ATPR) was studied as a poorly water-soluble model drug. The drug-loading and entrapment efficiency of the ATPR-loaded PAA-PPA micelles were 30.9 wt% and 87.9 %, respectively. The high drug-loading and entrapment efficiency were due to the synergistic effect of the micellar encapsulation and the binding interaction between drug and PAA-PPA. The ATPR-loaded PAA-PPA micelles showed a narrow size distribution, low zeta potential, high drug-loading capacity and good stable. The PAA-PPA was safer than Tween-80 and Cremophor EL (CrmEL) as an injectable pharmaceutical adjuvant for ATPR as indicated by the hemolysis and cytotoxicity studies. The novel amphiphilic amino acid copolymer can be considered as a prospective injectable delivery system for ATPR in terms of the pH-independent, greater drug-loading capacity and safety.

Preparation, physicochemical characteristics and bioavailability studies of an atorvastatin hydroxypropyl-beta-cyclodextrin complex.

The aim of this study was to improve the solubility, stability and bioavailability of amorphous atorvastatin calcium (AT) by complexing it with hydroxypropyl-beta-cyclodextrin. The formation of the inclusion complexation was identified by molecular modeling, phase solubility diagrams, differential scanning calorimetry and X-ray powder diffractometry. Orally Disintegrating Tablets (ODT) were then manufactured by direct compression. Apart from improved stability compared to pure AT, disintegration time of 27s, hardness of 5 kg and favorable mouth feel were achieved. In vitro dissolution tests of the ODT of AT inclusion complex exhibited higher dissolution rates than those with pure drug and the commercial tablet Lipitor. In vivo bioavailability studies in rats also showed shorter T(max), higher C(max) and increased AUC of 4.42 and 1.86 fold compared to the plain drug ODT and Lipitor. These results strongly suggest to use HP-beta-CD to improve the physicochemical characteristics and bioavailability of AT.

[Synthesis and characterization of N-octyl-N-arginine chitosan--a chitosan derivant with a mimetic structure of cell-penetrating peptides].

A novel chitosan derivant, N-octyl-N-arginine chitosan (OACS) with a mimetic structure of cell-penetrating peptides was synthesized by introducing hydrophilic arginine groups and hydrophobic octyl groups to the amino-group on chitosan's side chain. Structure of the obtained polymer was characterized by FT-IR and 1H NMR. The substitution degree of octyl and arginine groups was calculated through element analysis and spectrophotometric method, separately. The critical micelle concentration of OACS was 0.12 - 0.27 mgmL(-1) tested by fluorescence spectrometry. The solubility test showed OACS could easily dissolve in pH 1 - 12 solutions and self-assemble to form a micelle solution with light blue opalescence. The OACS micelles have a mean size of 158.4 - 224.6 nm, polydisperse index of 0.038 - 0.309 and a zeta potential of +19.16 - +30.80 mV determined by malvern zetasizer. AFM images confirmed free OACS micelle has a regular sphere form with a uniform particle size. MTT test confirmed that OACS was safe in 50 - 1 000 micromol-L(-1). The result of HepG2 cell experiment showed that the cell internalization of OACS micelles enhanced with increased substitution degree of arginine by 40 folds compared to chitosan. Thus, OACS micelles were a promising nano vehicle with permeation enhancement and drug carrier capability.