A Short Appraisal of Biomimetic Hydrogels to Improve Penetration of Poorly Permeable Drugs.

Effective drug delivery to target sites is critical for achieving desired therapeutic outcomes. However, the poor permeability of certain drugs poses significant challenges in achieving adequate drug concentrations at the desired locations. Biomimetic hydrogels have emerged as a promising approach to enhance the penetration of poorly permeable drugs. These hydrogels, designed to mimic natural biological systems, offer unique properties and functionalities that enable improved drug permeation. In this review, we provide a comprehensive appraisal of the role of biomimetic hydrogels in enhancing drug penetration. We discuss the design principles, properties, and mechanisms by which these hydrogels facilitate drug permeation. Specifically, we explore the applications and benefits of biomimetic hydrogels in controlled drug release, mimicking extracellular matrix microenvironments, promoting cell-mimetic interactions, and enabling targeted drug delivery. Through an examination of key studies and advancements, we highlight the potential of biomimetic hydrogels in enhancing drug penetration and their implications for therapeutic interventions. This review contributes to a deeper understanding of biomimetic hydrogels as a promising strategy for overcoming drug penetration challenges and advancing drug delivery systems, ultimately leading to improved therapeutic efficacy.

Monoclonal antibodies and antibody-drug conjugates as emerging therapeutics for breast cancer treatment.

When breast cells divide and multiply out of control, it is called breast cancer. Symptoms include lump formation in the breast, a change in the texture or color of the breast, or a discharge from the nipple. Local or systemic therapy is frequently used to treat breast cancer. Surgical and radiation procedures limited to the affected area are examples of local management. There has been significant worldwide progress in the development of monoclonal antibodies (mAbs) since 1986, when the first therapeutic mAb, Orthoclone OKT3, became commercially available. mAbs can resist the expansion of cancer cells by inducing the destruction of cellular membranes, blocking immune system inhibitors, and preventing the formation of new blood vessels. mAbs can also target growth factor receptors. Understanding the molecular pathways involved in tumor growth and its microenvironment is crucial for developing effective targeted cancer therapeutics. Due to their unique properties, mAbs have a wide range of clinical applications. Antibody-drug conjugates (ADCs) are drugs that improve the therapeutic index by combining an antigen-specific antibody with a payload. This review focuses on the therapeutic applications, mechanistic insights, characteristics, safety aspects, and adverse events of mAbs like trastuzumab, bevacizumab, pertuzumab, ertumaxomab, and atezolizumab in breast cancer treatment. The creation of novel technologies utilizing modified antibodies, such as fragments, conjugates, and multispecific antibodies, must be a central focus of future studies. This review will help scientists working on developing mAbs to treat cancers more effectively.

Strategies for drug targeting in pancreatic cancer.

BACKGROUND: Pancreatic cancer is expected to replace lung cancer as the second greatest cause of cancer mortality by 2025. It has been a particularly the most lethal kind of cancer. OBJECTIVE: Despite the new innovations, research, and improvements in drug design; there are many hurdles limiting their therapeutic applications such as intrinsic resistance to chemotherapeutics, inability to deliver a sufficient concentration of drug to the target site, lack of effectiveness of drug delivery systems. These are the major contributing factors to limit the treatment. So, the main objective is to overcome these types of problems by nanotechnology and ligand conjugation approach to achieve targeted drug delivery. METHOD: Nanotechnology has emerged as a major approach to develop cancer treatment. Regardless of the severity, there are several issues that restrict the therapeutic impact, including inadequate transport across biological barriers, limited cellular absorption, degradation, and faster clearance. RESULT: Targeted drug delivery may overcome these obstacles by binding a natural ligand to the surface of nanocarriers, which enhances the drug's capacity to release at the desired site and minimizes adverse effects. CONCLUSION: This study will investigate the possible outcomes of targeted therapeutic agent delivery in the treatment of pancreatic cancer, as well as the limitations and future prospects.

Changes in salivary output after induction at high-altitude areas and its effects on dental caries among Indian Army troops.

BACKGROUND: This study was aimed to evaluate the changes in salivary output and its effect on dental caries among Indian troops after 6 months of stay at high-altitude area (HAA). METHODS: All troops undergo mandatory dental checkup during acclimatization phase before deployment at HAA. Two thousand troops who fulfilled inclusion and exclusion criteria were selected, and consent for the study was obtained. Stimulated and unstimulated salivary samples were collected, the decayed, missing, and filled teeth (DMFT) index was evaluated, and required dental treatment was completed. The same salivary samples were collected after 6 months (on deinduction) to evaluate the salivary output. The DMFT index was re-evaluated to check the initiation of caries. RESULTS: The mean values of unstimulated and stimulated saliva at the initial visit were 4.105 and 17.03 gm, respectively, whereas the mean values of unstimulated and stimulated saliva after 180 days were 3.034 and 15.831 gm, respectively. Salivary flow was found to be significantly decreased after 6 months both in unstimulated and stimulated saliva. The mean DMFT at the time of induction of the study was 6.18 ± 3.03, and on deinduction, it was 7.22 ± 3.45 with p < 0.001, which was highly statistically significant. CONCLUSION: A decrease in body fluids and changed sympathetic and parasympathetic at HAA lead to decreased salivary secretions. Low water intake, high carbohydrate solid diet, negligible supply of fresh food, difficulty in maintenance of oral hygiene, and overall stress due to loneliness are all contributory factors for an increase in dental caries. It clearly demonstrates that prolonged stay at HAA affects salivary volume outflow, both stimulated and unstimulated, which has a corresponding effect on new caries.

Inhibitor of CBP Histone Acetyltransferase Downregulates p53 Activation and Facilitates Methylation at Lysine 27 on Histone H3.

Tumor suppressor p53-directed apoptosis triggers loss of normal cells, which contributes to the side-effects from anticancer therapies. Thus, small molecules with potential to downregulate the activation of p53 could minimize pathology emerging from anticancer therapies. Acetylation of p53 by the histone acetyltransferase (HAT) domain is the hallmark of coactivator CREB-binding protein (CBP) epigenetic function. During genotoxic stress, CBP HAT-mediated acetylation is essential for the activation of p53 to transcriptionally govern target genes, which control cellular responses. Here, we present a small molecule, NiCur, which blocks CBP HAT activity and downregulates p53 activation upon genotoxic stress. Computational modeling reveals that NiCur docks into the active site of CBP HAT. On CDKN1A promoter, the recruitment of p53 as well as RNA Polymerase II and levels of acetylation on histone H3 were diminished by NiCur. Specifically, NiCur reduces the levels of acetylation at lysine 27 on histone H3, which concomitantly increases the levels of trimethylation at lysine 27. Finally, NiCur attenuates p53-directed apoptosis by inhibiting the Caspase 3 activity and cleavage of Poly (ADP-ribose) polymerase (PARP) in normal gastrointestinal epithelial cells. Collectively, NiCur demonstrates the potential to reprogram the chromatin landscape and modulate biological outcomes of CBP-mediated acetylation under normal and disease conditions.

Prosthodontic Rehabilitation with a Telescopic Prosthesis of a Nonsyndromic Oligodontia Patient.

Oligodontia is the congenital absence of six or more permanent teeth, excluding the third molars. Oligodontia of permanent dentition is a rare occurrence. Preservation of the remaining deciduous dentition in such situations is important for both functional and esthetic rehabilitation of the patient. This clinical report describes the rehabilitation of a 16-year-old male with oligodontia of permanent teeth treated by an interdisciplinary team of prosthodontist, pedodontist, and orthodontist. The remaining deciduous dentition was endodontically treated. Occlusal vertical dimension (OVD) of the deciduous dentition was assessed. A full-mouth single piece porcelain-fused-to-metal telescopic prosthesis for the maxillary and mandibular arches was planned with a minimal increase in OVD. The telescopic prosthesis provided excellent retention, stability, esthetics, and stress equalization on the remaining deciduous dentition. Maintenance of oral hygiene procedures was simplified for the adolescent with the telescopic prosthesis. Preservation of remaining deciduous dentition and fabrication of a telescopic prosthesis in this patient provided an effective esthetic and functional rehabilitation.

A clinico radiographic study of immediate loading implants in rehabilitation of mandibular ridges.

BACKGROUND: Numerous studies regarding the immediate loading of splinted implants retaining/supporting mandibular dentures have reported promising results, but studies comparing splinted and unsplinted attachments for supporting overdentures with immediate loading are limited. Scientific literature is sparse comparing various attachment systems and patient satisfaction in response to immediately loaded implant supported overdentures. METHODS: A total of 30 completely edentulous patients male or female, in the age group of 54-78 years (mean age 65 years), wearing conventional complete dentures were selected and randomly divided in to two groups. A total of 60 implants were placed in the interforaminal area of the mental symphysis (two implants per patients) in 30 patients. Two types of attachment systems namely Ball for group-A and Bar for group-B were used and immediate loading done. Implants were evaluated clinically and radiographically at baseline, 1 month, 3 months, 6 months and 9 months. All clinical and radiographic parameters were subjected to statistical analysis. RESULT: The implant survival rate for group-A (ball attachment) was 93.3% and implant survival rate for group-B (bar attachment) was 93.3%. The overall implant survival rate was not dependent on the attachment system. There was no significant difference in the crestal bone loss in mesial, and distal side in implants with respect to ball and bar attachment for different period of observation (F = 0.25; P = 0.910; F = 0.07; P = 0.992 respectively). CONCLUSION: Overdenture supported by two implants should be the minimum gold standard in the rehabilitation of completely edentulous patients.

Surface characterization of nickel titanium orthodontic arch wires.

BACKGROUND: Surface roughness of nickel titanium orthodontic arch wires poses several clinical challenges. Surface modification with aesthetic/metallic/non metallic materials is therefore a recent innovation, with clinical efficacy yet to be comprehensively evaluated. METHODS: One conventional and five types of surface modified nickel titanium arch wires were surface characterized with scanning electron microscopy, energy dispersive analysis, Raman spectroscopy, Atomic force microscopy and 3D profilometry. Root mean square roughness values were analyzed by one way analysis of variance and post hoc Duncan's multiple range tests. RESULTS: Study groups demonstrated considerable reduction in roughness values from conventional in a material specific pattern: Group I; conventional (578.56 nm) > Group V; Teflon (365.33 nm) > Group III; nitride (301.51 nm) > Group VI (i); rhodium (290.64 nm) > Group VI (ii); silver (252.22 nm) > Group IV; titanium (229.51 nm) > Group II; resin (158.60 nm). It also showed the defects with aesthetic (resin/Teflon) and nitride surfaces and smooth topography achieved with metals; titanium/silver/rhodium. CONCLUSIONS: Resin, Teflon, titanium, silver, rhodium and nitrides were effective in decreasing surface roughness of nickel titanium arch wires albeit; certain flaws. Findings have clinical implications, considering their potential in lessening biofilm adhesion, reducing friction, improving corrosion resistance and preventing nickel leach and allergic reactions.

Comparison of articulating paper markings and T Scan III recordings to evaluate occlusal force in normal and rehabilitated maxillofacial trauma patients.

BACKGROUND: Prosthodontic Rehabilitation of Treated Maxillofacial Trauma Cases by Evaluating Occlusal Force Distribution Using Computerized Occlusal Analysis. METHOD: 30 patients were selected for the study. 15 normal and 15 treated trauma patients were subjected to T Scan analysis and evaluated for the occlusal force distribution. RESULTS: The results take into consideration the two parameters. Firstly the largest articulating paper mark (photographed) and secondly the T scan of the same patient. Comparison was made between the largest articulating paper mark and highest force tooth in the quadrant using T Scan. The matches and no matches were then tabulated for statistical analysis assessing the frequency of the matches to the no matches. CONCLUSION: The ultimate advantage of a T Scan III analysis is that it can detect the amount of force as well as location of the highest intensity contacts of a single tooth which is very specific.

Clinical evaluation of overdenture retention using indigenous dental implants.

BACKGROUND: The continuous resorption of the alveolar ridge after extraction of all the teeth can eventually result in a jaw anatomy which offers inadequate support for the dentures. This resorption can render the prosthesis inadequate in terms of both function and esthetics. METHODS: A study was conducted where 50 edentulous, denture-wearing patients, of either sex, were given mandibular implant overdentures, using their existing denture. The implants used were one piece implants with an integrated ball and socket joint for retention. A healing time of 3-4 months was given before loading. RESULTS: Implant failure was seen in 11 cases during the healing phase. A success rate of 78% was seen in this study during an observation period of 6 months. This success rate is significantly low as compared to global records where a success rate of 87-98% is documented. The patients were asked to grade the overdenture as poor, satisfactory, good and excellent in categories of masticatory efficiency, speech and overall comfort. 71.79% patients rated the overall comfort as excellent and the same percentage of patients rated the speech as good. CONCLUSION: Implant retained overdentures help in improving the masticatory efficiency, speech and overall comfort of the patient as compared to conventional dentures.

Transparent magnesium aluminate spinel: a prospective biomaterial for esthetic orthodontic brackets.

Adult orthodontics is recently gaining popularity due to its importance in esthetics, oral and general health. However, none of the currently available alumina or zirconia based ceramic orthodontic brackets meet the esthetic demands of adult patients. Inherent hexagonal lattice structure and associated birefringence limits the visible light transmission in polycrystalline alumina and make them appear white and non transparent. Hence focus of the present study was to assess the feasibility of using magnesium aluminate (MgAl2O4) spinel; a member of the transparent ceramic family for esthetic orthodontic brackets. Transparent spinel specimens were developed from commercially available white spinel powder through colloidal shaping followed by pressureless sintering and hot isostatic pressing at optimum conditions of temperature and pressure. Samples were characterized for chemical composition, phases, density, hardness, flexural strength, fracture toughness and optical transmission. Biocompatibility was evaluated with in-vitro cell line experiments for cytotoxicity, apoptosis and genotoxicity. Results showed that transparent spinel samples had requisite physico-chemical, mechanical, optical and excellent biocompatibility for fabricating orthodontic brackets. Transparent spinel developed through this method demonstrated its possibility as a prospective biomaterial for developing esthetic orthodontic brackets.

Prospective study of treatment outcome of implant retained mandibular overdenture: Two years follow-up.

AIMS: The aim of this study is to evaluate the treatment outcome of immediately loaded Implants in the interforaminal region of anterior mandible. MATERIALS AND METHODS: A total of 15 completely edentulous patients aged between 50 and 70 years were selected satisfying certain inclusion and exclusion criteria. Two implants were placed in 33 and 43 region (B and D location) and the implants were loaded immediately by mandibular overdenture retained with O-ring attachments. The implants were evaluated for various clinical parameters at 6 months, 1 year, 1.5 years, and 2 years intervals after initial placement. RESULTS: There was increased marginal bone loss around implants during the 1(st) year after that the bone loss was insignificant. Clinical stability of immediately loaded implants was lower initially for 6 months, but improved by the end of 1(st) year. Survival rate for immediately loaded implants was 96.6% at the end of the period of study. CONCLUSION: Immediate loading of interforaminal mandibular implants demonstrated a highly acceptable clinical success at the end of 2 years. However, initially the marginal bone level and clinical stability were significantly lower which showed improvement with time.

Clinical evaluation of immediate implants using different types of bone augmentation materials.

BACKGROUND: The immediate placement of implants into fresh extraction socket has proven to be a safe and predictable procedure. However, there is lack of scientific evidence regarding the healing pattern and osseointegration associated with immediate implants especially with different grafting materials. METHODS: A total of 30 patients male or female, with a mean age of 23.1 years ± 6.0 in the age group of 18-38 years, each having at least one tooth indicated for extraction (either maxillary or mandibular anterior teeth) were selected and randomly divided in to two groups. 30 Implants (Xive(®) friadent, Germany) were placed into fresh extraction sockets during this study. Two types of graft materials namely Dembone(®) (freeze-dried bone allograft) for group A and G-Bone(®) (modified hydroxyapatite) for group B were used. After implant placement all implants were evaluated clinically and radiographically at baseline, 3 months, 6 months, 9 months and 12 months. All clinical and radiographic parameters were subjected to statistical analysis. Intragroup comparisons were made with paired 't' test and intergroup comparisons with unpaired 't' test (P > 0.05 NS, ≤0.05 S, ≤0.01 HS). RESULT: During the 1-year interval, no implant was lost and the mean bone level at the implants was maintained or even improved. CONCLUSION: Immediate restoration of single tooth implants placed in fresh extraction sockets could be considered a valuable option to replace a missing tooth. The graft materials used in both groups have been found to be equally effective.

Orthodontic management of dentition in patients with periodontally compromised dentition.

BACKGROUND: An increasing number of adult patients are seeking orthodontic treatment to improve their dental appearance. However, special attention must be given to the periodontal status of the adults as periodontal disease and its sequel, such as pathologic migration of anterior teeth, result in esthetic and functional problems. In such adult patients, an interdisciplinary approach often offers the best option for achieving a predictable outcome to solve complex clinical problems. MATERIALS AND METHODS: A prospective study was carried out on 20 adult patients [mean age = 33.3 ± 4.52 (SD), 11 females and nine males] with periodontally compromised and malaligned dentition. Loe and Silness Gingival Index (GI), Ramfjord's Periodontal Disease Index (PDI) and Dental Aesthetic Index (DAI) were recorded at the start and after completion of treatment. RESULTS: Comparison of GI, PDI and DAI before and after completion of treatment showed statistically significant differences, indicating the relevance of combined orthodontic-periodontic treatment in periodontally compromised dentition (P < 0.01). CONCLUSION: The outcome of the study showed that an interdisciplinary approach is a simple solution for complex clinical problems arising as a sequel to periodontitis, such as pathological tooth migration, restoring function, esthetics and periodontal health.

Comparative evaluation of retentive properties of acid etched resin bonded fixed partial dentures.

BACKGROUND: Little consensus exist in suitable tooth preparation design and alloy pre-treatment methods for improving the retention of resin bonded fixed partial dentures (RBFPDs). METHODS: An in-vitro experiment was done with four designs. Group A: standard form, B: wings and proximal slices, C: wings, proximal slice and grooves, D: wings, proximal slice, grooves and occlusal coverage. Alloys were subjected to pre-treatment procedures like Group I: control, II: sand blasting, III: electro etching, IV: tin plating. Debonding forces of the castings were recorded in a universal testing machine and results were analyzed by student's 't' test. RESULTS: Group B, C and D showed higher debonding forces compared to A. However, there were no significant differences in mean force values among Groups B, C and D. Group II, III and IV with different alloy pre-treatment methods demonstrated higher values against control. Inter group variations among Group II, III and IV were not significant. CONCLUSION: Tooth preparation with adequate surface extensions and pre-treatment procedures of casting alloys are two parameters that play important role in determining the retentive features of RBFPDs. Different types of tooth preparation designs and alloy pre-treatment methods exert almost similar influence in increasing the retention of acid etched RBFPDs.

Laser ionization mass spectrometry in oral squamous cell carcinoma.

Biomarker research in oral squamous cell carcinoma (OSCC) aims for screening/early diagnosis and in predicting its recurrence, metastasis and overall prognosis. This article reviews the current molecular perspectives and diagnosis of oral cancer with proteomics using matrix-assisted laser desorption ionization (MALDI) and surface-enhanced laser desorption ionization (SELDI) mass spectrometry (MS). This method shows higher sensitivity, accuracy, reproducibility and ability to handle complex tissues and biological fluid samples. However, the data interpretation tools of contemporary mass spectrometry still warrant further improvement. Based on the data available with laser-based mass spectrometry, biomarkers of OSCC are classified as (i) diagnosis and prognosis, (ii) secretory, (iii) recurrence and metastasis, and (iv) drug targets. Majority of these biomarkers are involved in cell homeostasis and are either physiologic responders or enzymes. Therefore, proteins directly related to tumorigenesis have more diagnostic value. Salivary secretory markers are another group that offers a favourable and easy strategy for non-invasive screening and early diagnosis in oral cancer. Key molecular inter-related pathways in oral carcinogenesis are also intensely researched with software analysis to facilitate targeted drug therapeutics. The review suggested the need for incorporating 'multiple MS or tandem approaches' and focusing on a 'group of biomarkers' instead of single protein entities, for making early diagnosis and treatment for oral cancer a reality.

Corrosion resistance of surface modified nickel titanium archwires.

OBJECTIVE: To compare the corrosion behavior of commercially available surface modified nickel titanium (NiTi) arch wires with respect to a conventional NiTi and to evaluate its association with surface characteristics. MATERIALS AND METHODS: Five types of surface modified arch wires and a conventional NiTi arch wire, all from different manufacturers, were evaluated for their corrosion resistance from breakdown potential in an anodic polarization scan in Ringer's solution. Surface characteristics were determined from scanning electron microscopy, atomic force microscopy, and energy dispersive analysis. One-way analysis of variance and post hoc Duncan's multiple range tests were used to evaluate statistical significance. RESULTS: Surface modified NiTi wires showed significant improvement in corrosion resistance and reduction in surface roughness values. Breakdown potentials increased in the order of group 6 (conventional; 204 mV) < group 1 (nitride; 333 mV) < group 5 (epoxy resin; 346mV) < group 3 (oxide; 523 mV) < group 2 (gold; 872 mV) < group 4 (Teflon; 1181 mV), but root mean square (RMS) roughness values, which indicated surface roughness, followed a different pattern: group 3 (oxide; 74.12 nm) < group 1 (nitride; 221.651 nm) < group 4 (Teflon; 278.523 nm) < group 2 (gold; 317.894 nm) < group 5 (epoxy resin; 344.236 nm) < group 6 (conventional; 578.555 nm). CONCLUSIONS: Surface modification of NiTi wires proved to be effective in improving its corrosion resistance and decreasing surface roughness. However, neither factor could maintain a direct, one-to-one relationship. It meant that the type and nature of coating material can effectively influence the anticorrosive features of NiTi wires, compared with its surface roughness values.

Comparative evaluation of 15% ethylenediamine tetra-acetic acid plus cetavlon and 5% chlorine dioxide in removal of smear layer: A scanning electron microscope study.

AIMS: The purpose of this study was to compare the efficacy of smear layer removal by 5% chlorine dioxide and 15% Ethylenediamine Tetra-Acetic Acid plus Cetavlon (EDTAC) from the human root canal dentin. MATERIALS AND METHODS: Fifty single rooted human mandibular anterior teeth were divided into two groups of 20 teeth each and control group of 10 teeth. The root canals were prepared till F3 protaper and initially irrigated with 2% Sodium hypochlorite followed by 1 min irrigation with 15% EDTAC or 5% Chlorine dioxide respectively. The control group was irrigated with saline. The teeth were longitudinally split and observed under Scanning electron microscope SEM (×2000). STATISTICAL ANALYSIS USED: The statistical analysis was done using General Linear Mixed Model. RESULTS: At the coronal thirds, no statistically significant difference was found between 15% EDTAC and 5% Chlorine dioxide in removing smear layer. In the middle and apical third region 15% EDTAC showed better smear layer removal ability than 5% Chlorine dioxide. CONCLUSION: Final irrigation with 15% EDTAC is superior to 5% chlorine dioxide in removing smear layer in the middle and apical third of radicular dentin.