Tooth agenesis related to a novel KDF1 variant: A case report and literature review.

OBJECTIVES: To investigate the role of Keratinocyte Differentiation Factor 1 (KDF1) in ectodermal dysplasia (ED) and nonsyndromic tooth agenesis (NSTA) and perform a literature review. METHODS: Genome sequencing was used to identify genetic variants in a Thai, NSTA proband and validated through Sanger sequencing. Pathogenicity was assessed using ACMG guidelines, MetaRNN and AlphaMissense. A comprehensive review of KDF1/NSTA cases informed genotype-phenotype analysis of the proband. RESULTS: The proband revealed multiple missing teeth, caries and extensive periodontal disease. Deep phenotyping showed no signs of ED beyond tooth agenesis. The identified novel KDF1 variant, p.Ile243Leu, was classified as 'likely pathogenic' by ACMG and predicted as 'detrimental' by MetaRNN and AlphaMissense analyses. A total of 14 reviewed KDF1 cases revealed ED-associated variants (3 variants in 8 patients) clustering in the region of amino acids 251-275, within the DUF4656 domain, while NSTA-causing variants (4 variants in 6 patients) were typically found in amino- or carboxy-termini to this region. KDF1/NSTA cases exhibited an average of 15 missing teeth, with a higher prevalence in the mandible. CONCLUSION: This study identifies a novel KDF1 variant-related NSTA in Thai people. The genotype-phenotype correlates suggest a distinctive pattern and tooth agenesis of KDF1-related NSTA.

Green-synthesized silver nanoparticles from Zingiber officinale extract: antioxidant potential, biocompatibility, anti-LOX properties, and in silico analysis.

INTRODUCTION: Zingiber officinale extract has emerged as a compelling candidate for green synthesis of nanoparticles, offering diverse applications across medicine, cosmetics, and nutrition. This study delves into the investigation of in vitro toxicity and explores the biomedical utility of green-synthesized silver nanoparticles derived from ginger extract (GE-AgNPs). METHODS: We employed established protocols to evaluate in vitro aspects such as antioxidant capacity, anti-inflammatory potential, and biocompatibility of GE-AgNPs. Additionally, molecular docking was employed to assess their anti-lipoxygenase (anti-LOX) activity. RESULTS: Our findings highlight that the extraction of ginger extract at a pH of 6, utilizing a cosolvent blend of ethanol and ethyl acetate in a 1:1 ratio, yields heightened antioxidant capacity attributed to its rich phenolic and flavonoid content. In the context of silver nanoparticle synthesis, pH 6 extraction yields the highest quantity of nanoparticles, characterized by an average size of 32.64 ± 1.65 nm. Of particular significance, GE-AgNPs (at pH 6) demonstrated remarkable efficacy in scavenging free radicals, as evidenced by an IC50 value of 6.83 ± 0.47 µg/mL. The results from the anti-LOX experiment indicate that GE-AgNPs, at a concentration of 10 µg/mL, can inhibit LOX activity by 25%, outperforming ginger extract which inhibits LOX by 17-18%. Notably, clionasterol exhibited higher binding energy and enhanced stability (-8.9 kcal/mol) compared to nordihydroguaiaretic acid. Furthermore, a cell viability study confirmed the safety of GE-AgNPs at a concentration of 17.52 ± 7.00 µg/mL against the L929 cell line. CONCLUSION: These comprehensive findings underscore the significant biomedical advantages of GE-AgNPs and emphasize their potential incorporation into cosmetic products at a maximum concentration of 10 µg/mL.

Artificial Intelligence-Based Diagnosis of Oral Lichen Planus Using Deep Convolutional Neural Networks.

OBJECTIVE: The aim of this study was to employ artificial intelligence (AI) via convolutional neural network (CNN) for the separation of oral lichen planus (OLP) and non-OLP in biopsy-proven clinical cases of OLP and non-OLP. MATERIALS AND METHODS: Data comprised of clinical photographs of 609 OLP and 480 non-OLP which diagnosis has been confirmed histopathologically. Fifty-five photographs from the OLP and non-OLP groups were randomly selected for use as the test dataset, while the remaining were used as training and validation datasets. Data augmentation was performed on the training dataset to increase the number and variation of photographs. Performance metrics for the CNN model performance included accuracy, positive predictive value, negative predictive value, sensitivity, specificity, and F1-score. Gradient-weighted class activation mapping was also used to visualize the important regions associated with discriminative clinical features on which the model relies. RESULTS: All the selected CNN models were able to diagnose OLP and non-OLP lesions using photographs. The performance of the Xception model was significantly higher than that of the other models in terms of overall accuracy and F1-score. CONCLUSIONS: Our demonstration shows that CNN models can achieve an accuracy of 82 to 88%. Xception model performed the best in terms of both accuracy and F1-score.

Alginate/pectin dressing with niosomal mangosteen extract for enhanced wound healing: evaluating skin irritation by structure-activity relationship.

Most modern wound dressings assist the wound-healing process. In contrast, conventional wound dressings have limited antibacterial activity and promote sporadic fibroblast growth. Therefore, wound dressings with prolonged substance release must be improved. This research aimed to develop hydrogel films. These were synthesized from alginate and pectin, incorporated with mangosteen extract (ME), and encapsulated in niosomes (ME-loaded niosomes). Subsequently, we examined the in vitro release and physical characteristics of ME-loaded niosomes. These characteristics included particle pH, size, charge, polydispersity index (PDI), and drug loading properties. These properties included drug loading content (DLC), entrapment efficiency (EE), and yield (Y). Additionally, we examined the swelling ratio and biological characteristics of the hydrogel film. These characteristics included antibacterial activity, cytotoxicity (L929), cell attachment to the tested materials, cell migration, hemocompatibility, and in vivo irritation. Significant results were obtained using a 2:1 niosome preparation containing Span60 and cholesterol. Ratio influenced size, charge, PDI, DLC, EE, and Y. The results were 225.5 ± 5.83 nm, negatively charged, 0.38, 16.2 ± 0.87%, 64.8 ± 3.49%, and 87.3 ± 3.09%, respectively. Additionally, the release of encapsulated ME was pH sensitive because 85% of the ME can be released at a pH of 5.5 within seven days and decrease to 70% at a pH of 7.4. The maximum swelling ratios of patches with 0.5% and 1% Ca2+ crosslinking were 867 wt% and 1,025 wt%, respectively, after 30 min. These results suggested that a medium dose (15 mg) of niosomal ME incorporated in a hydrogel film provided better bacterial inhibition, cell migration, and cell adhesion in an in vitro model. Additionally, no toxicity was observed in the fibroblasts and red blood cells. Therefore, given the above-mentioned advantages, this product can be a promising candidate for wound dressing applications.

Preparation and Characterization of Porous Poly(Lactic Acid)/Poly(Butylene Adipate-Co-Terephthalate) (PLA/PBAT) Scaffold with Polydopamine-Assisted Biomineralization for Bone Regeneration.

The development of scaffolds that simultaneously provide porous architectures and osteogenic properties is the major challenge in tissue engineering. Herein, a scaffold with high porosity and well interconnected networks, namely poly(lactic acid)/poly(butylene adipate-co-terephthalate) (PLA/PBAT), was fabricated using the gas foaming/ammonium bicarbonate particulate leaching technique. Mussel-inspired polydopamine (PDA)-assisted biomineralization generated by two-step simple soaking in dopamine solution and 10× SBF-like solution was performed to improve the material's osteogenicity. Highly porous scaffolds available in less organized opened cell structures with diameters ranging from 10 µm to 100 µm and 200 µm to 500 µm were successfully prepared. The well interconnected porous architectures were observed through the whole thickness of the scaffold. The even deposition of the organic-inorganic bioactive mineralized layer composed of PDA and nano-scale hydroxyapatite (HA) crystals on the scaffold surface was evidenced by scanning electron microscopy (SEM), energy-dispersive X-ray analysis (EDX), Fourier transform infrared spectroscopy (FTIR), and X-ray diffraction (XRD). The developed scaffold exhibited high total porosity (84.17 ± 1.29%), a lower surface contact angle (θ = 45.7 ± 5.9°), lower material degradation rate (7.63 ± 2.56%), and a high level of material biocompatibility. The MTT assay and Alizarin Red S staining (ARS) confirmed its osteogenic enhancement property toward human osteoblast-like cells (MG-63). These results clarified that the developed porous PLA/PBAT scaffold with PDA-assisted biomineralization exhibited good potential for application as a biomaterial for bone tissue regeneration and hard tissue engineering.

Development of Nanoemulsions for Wound Dressings Containing Cassia alata L. Leaf Extraction.

Natural polymer-based hydrogel films possess considerable potential for use in biomedical applications and are excellent for wound healing. The purpose of this research was to use ionic crosslinking to improve the mechanical characteristics, absorption of fluid in the wound, and drug release behavior of Cassia alata L. (CA) extract loaded niosomes (CANs) that were incorporated in an alginate-pectin film (A/P). Then, chemically crosslinked A/P hydrogels were obtained by immersing them in different concentrations of calcium chloride (CaCl2) (0.5-1% w/v) for 15-120 s. The degree of crosslinking was controlled by both contact time and CaCl2 concentration. The optimal crosslinking conditions were 1% CaCl2 for 15 seconds. In this study, the following features of the hydrogel films were investigated: physical properties, morphological characteristics, drug loading, in vitro drug release, antibacterial activity, wound healing activity, cytocompatibility profiles, and hemocompatibility. The crosslinked hydrogel films maintained their physical integrity during use, with the 1% film attaining the best results in the shortest period (15 sec). Then, in vitro drug release from the films was examined. Crosslinking was observed to prolong the release of the CA extract from the hydrogel film. Finally, a cell viability experiment was conducted to evaluate the cytotoxicity profile. The A/P composite film exhibited excellent wound dressing qualities and good mechanical properties in preformulation testing. The in vitro drug release profile indicated that the A/P created a regulated drug release profile, and the cell viability experiment revealed that the film was nontoxic and hemocompatible. A/P composite films can be produced using CAN extract as a possible wound dressing. However, further studies in animals and humans are required to determine both safety and effectiveness.

In silico investigation of ACE2 and the main protease of SARS-CoV-2 with phytochemicals from Myristica fragrans (Houtt.) for the discovery of a novel COVID-19 drug.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19), is a new coronavirus strain that was first reported in December 2019 in Wuhan, China. A specific treatment for COVID-19 has yet to be identified. Potential therapeutic targets include SARS-CoV-2 main protease (Mpro) and the SARS-CoV-2 spike-ACE2 interaction. Molecular docking, molecular dynamics (MD), solvent screening for the extraction of the specified compounds, and prediction of the drug properties of certain molecules were the methods used in this study to investigate compounds from the medicinal plant Myristica fragrans, which is one of twelve herbs in Prasachandaeng remedy (PSD). ArgusLab, AutoDock Vina, and AutoDock were used to perform docking tasks. The examined ligands were compared with panduratin A as a standard (Kanjanasirirat et al., 2020), which is a promising medicinal plant molecule for the treatment of COVID-19. Molecular docking revealed that malabaricones B and C and licarins A, B and C bound to SARS-CoV-2/ACE2 and SARS-CoV-2 Mpro with low binding energies compared to that of the standard ligand. Furthermore, appropriate solvent usage is important. Acetone was selected by COSMOquick software for compound extraction in this investigation because it can extract large amounts of all five of the abovementioned M. fragrans compounds. Furthermore, the drug-like properties of these compounds were studied utilizing the Lipinski, Veber, and Ghose criteria. The results revealed that these M. fragrans compounds have potential as effective medicines to combat the COVID-19 pandemic. However, to assess the therapeutic potential of these ligands, additional research is needed, which will use our findings as a foundation.

Automatic Programmable Bioreactor with pH Monitoring System for Tissue Engineering Application.

Tissue engineering technology has been advanced and applied to various applications in the past few years. The presence of a bioreactor is one key factor to the successful development of advanced tissue engineering products. In this work, we developed a programmable bioreactor with a controlling program that allowed each component to be automatically operated. Moreover, we developed a new pH sensor for non-contact and real-time pH monitoring. We demonstrated that the prototype bioreactor could facilitate automatic cell culture of L929 cells. It showed that the cell viability was greater than 80% and cell proliferation was enhanced compared to that of the control obtained by a conventional cell culture procedure. This result suggests the possibility of a system that could be potentially useful for medical and industrial applications, including cultured meat, drug testing, etc.

Expanding the genotypic spectrum of PYCR2 and a common ancestry in Thai patients with hypomyelinating leukodystrophy 10.

PYCR2 pathogenic variants lead to an autosomal recessive hypomyelinating leukodystrophy 10 (HLD10), characterized by global developmental delay, microcephaly, facial dysmorphism, movement disorder, and hypomyelination. This study identified the first two unrelated Thai patients with HLD10. Patient 1 harbored the novel compound heterozygous variants, c.257T>G (p.Val86Gly) and c.400G>A (p.Val134Met), whereas patient 2 possessed the homozygous variant, c.400G>A (p.Val134Met), in PYCR2. Haplotype analysis revealed that the two families' members shared a 2.3 Mb region covering the c.400G>A variant, indicating a common ancestry. The variant was estimated to age 1450 years ago. Since the c.400G>A was detected in three out of four mutant alleles and with a common ancestry, this variant might be common in Thai patients. We also reviewed the phenotype and genotype of all 35 previously reported PYCR2 patients and found that majorities of cases were homozygous with a consanguineous family history, except patient 1 and another reported case who were compound heterozygous. All patients had microcephaly and developmental delay. Hypotonia and peripheral spasticity were common. Hypomyelination or delayed myelination was a typical radiographic feature. Here, we report the first two Thai patients with HLD10 with the novel PYCR2 variants expanding the genotypic spectrum and suggest that the c.400G>A might be a common mutation in Thai patients.

Human dental pulp stem cell responses to different dental pulp capping materials.

BACKGROUND: Direct pulp capping is a vital pulp therapy for a pin-point dental pulp exposure. Applying a pulp capping material leads to the formation of a dentin bridge and protects pulp vitality. The aim of this study was to compare the effects of four dental materials, DyCal®, ProRoot® MTA, Biodentine™, and TheraCal™ LC in vitro. METHODS: Human dental pulp stem cells (hDPs) were isolated and characterized. Extraction medium was prepared from the different pulp capping materials. The hDP cytotoxicity, proliferation, and migration were examined. The odonto/osteogenic differentiation was determined by alkaline phosphatase, Von Kossa, and alizarin red s staining. Osteogenic marker gene expression was evaluated using real-time polymerase chain reaction. RESULTS: ProRoot® MTA and Biodentine™ generated less cytotoxicity than DyCal® and TheraCal™ LC, which were highly toxic. The hDPs proliferated when cultured with the ProRoot® MTA and Biodentine™ extraction media. The ProRoot® MTA and Biodentine™ extraction medium induced greater cell attachment and spreading. Moreover, the hDPs cultured in the ProRoot® MTA or Biodentine™ extraction medium migrated in a similar manner to those in serum-free medium, while a marked reduction in cell migration was observed in the cells cultured in DyCal® and TheraCal™ LC extraction media. Improved mineralization was detected in hDPs maintained in ProRoot® MTA or Biodentine™ extraction medium compared with those in serum-free medium. CONCLUSION: This study demonstrates the favorable in vitro biocompatibility and bioactive properties of ProRoot® MTA and Biodentine™ on hDPs, suggesting their superior regenerative potential compared with DyCal® and TheraCal™.

Delayed response to proton beam treatment of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) has become one of the leading causes of cancer death worldwide. There has been anecdotal report regarding the effectiveness of proton beam treatment for HCC. In this pre-clinical investigation, the woodchuck model of viral hepatitis infection-induced HCC was used for proton beam treatment experiment. The radiopaque fiducial markers that are biodegradable were injected around the tumor under ultrasound guidance to facilitate positioning in sequential treatments. An α cradle mode was used to ensure reproducibility of animal positioning on the treatment couch. A CT scan was performed first for contouring by a radiation oncologist. The CT data set with contours was then exported for dose planning. Three fractionations, each 750 CcGyE, were applied every other day with a Mevion S250 passive scattering proton therapy system. Multiphase contrast-enhanced CT scans were performed after the treatment and at later times for follow-ups. 3 weeks post-treatment, shrinking of the HCC nodule was detected and constituted to a partial response (30% reduction along the long axis). By week nine after treatment, the nodule disappeared during the arterial phase of multiphase contrast-enhanced CT scan. Pathological evaluation corroborated with this imaging response. A delayed, but complete imaging response to proton beam treatment applied to HCC was achieved with this unique and clinically relevant animal model of HCC.

Increasing Distribution of Drugs Released from In Situ Forming PLGA Implants Using Therapeutic Ultrasound.

One of the challenges in developing sustained-release local drug delivery systems is the limited treatment volume that can be achieved. In this work, we examine the effectiveness of using low frequency, high intensity ultrasound to promote the spatial penetration of drug molecules away from the implant/injection site boundary upon release from injectable, phase inverting poly(lactic acid-co-glycolic acid) (PLGA) implants. Fluorescein-loaded PLGA solutions were injected into poly(acrylamide) phantoms, and the constructs were treated daily for 14 days with ultrasound at 2.2 W/cm2 for 10 min. The 2D distribution of fluorescein within the phantoms was quantified using fluorescence imaging. Implants receiving ultrasound irradiation showed a 1.7-5.6 fold increase (p < 0.05) in fluorescence intensity and penetration distance, with the maximum increase observed 5 days post-implantation. However, this evidence was not seen when the same experiment was also carried out in phosphate buffer saline (pH 7.4). Results suggest an active role of ultrasound in local molecular transport in the phantom. An increase of fluorescein release and penetration depth in phantoms can be accomplished through brief application of ultrasound. This simple technique offers an opportunity to eventually enhance the therapeutic efficacy and broaden the application of local drug delivery systems.

Paclitaxel-loaded polymeric depots as injectable drug delivery system for cancer chemotherapy of hepatocellular carcinoma.

In this work, paclitaxel-encapsulated polymeric depots were prepared and characterized as drug delivery system for cancer chemotherapy against hepatocellular carcinoma. Effects of different parameters, including drug-loading content, polymer concentration and depot weight on depot formation, percentage of sustained-release taxol and drug release profile were evaluated. Paclitaxel-loaded depots were successfully formed at the polymer concentration above 25% w/v. For all formulations, paclitaxel could be encapsulated with very high percentage of sustained-release taxol (>90%). The release rate of paclitaxel from depots could be controlled by the amount of drug-loading content, polymer concentration and depot weight. Cytotoxicity against liver cancer cell line, HepG2, was evaluated by medium extraction method. Paclitaxel releasing from depots showed cytotoxic effect against HepG2 at different incubation times, whereas blank depots exhibited no cytotoxicity.

Injectable SN-38-loaded Polymeric Depots for Cancer Chemotherapy of Glioblastoma Multiforme.

PURPOSE: SN-38, a potent chemotherapeutic drug, has not been used clinically because of its severe side effects and poor solubility. In this work, we aimed to evaluate the effect of dose and multiple injections of SN-38-loaded polymeric depots on antitumor efficacy and toxicity in vivo. METHODS: Preparation and characterization of SN-38-loaded depots were performed and evaluated in vitro using human glioblastoma cell line, U-87MG. Antitumor efficacy with different depot administrations including dose, position of depot injection and number of injections were evaluated in tumor model in nude mice. RESULTS: Depots encapsulated SN-38 with high encapsulation efficiency (~98.3%). High amount of SN-38 (3.0 ± 0.1 mg) was prolonged and controlled release over time and showed anticancer activity against U-87MG cell line in vitro. For one course administration, depots exhibited better antitumor efficacy and reduced toxicity compared to free SN-38. Elevated doses and multiple injections of SN-38-loaded depots and free SN-38 provided greater tumor growth inhibition and animal survival. All animals received SN-38-loaded depots were well tolerated and survived while most of those received free SN-38 died at day 30. Free SN-38 showed severe toxic effect compared to minimal toxicity from SN-38-loaded depots which was due to lower SN-38 level in systemic circulation. Fluorescence imaging and histopathology confirmed that SN-38 released from depots was detected throughout tumors 35 days post administration. CONCLUSIONS: SN-38-loaded depots were proved as a promising new treatment for highly invasive glioblastoma multiforme with low acute toxicity due to controlled release of SN-38.

Antitumor efficacy and intratumoral distribution of SN-38 from polymeric depots in brain tumor model.

We investigate antitumor efficacy and 2D and 3D intratumoral distribution of 7-ethyl-10-hydroxycamptothecin (SN-38) from polymeric depots inside U-87MG xenograft tumor model in nude mice. Results showed that polymeric depots could be used to administer and controlled release of a large amount of SN-38 directly to the brain tumor model. SN-38 released from depots suppressed tumor growth, where the extent of suppression greatly depended on doses and the number of depot injections. Tumor suppression of SN-38 from depots was three-fold higher in animals which received double injections of depots at high dose (9.7 mg of SN-38) compared to single injection (2.2 mg). H&E staining of tumor sections showed that the area of tumor cell death/survival of the former group was two-fold higher than those of the latter group. Fluorescence imaging based on self-fluorescent property of SN-38 was used to evaluate the intratumoral distribution of this drug compared to histological results. The linear correlation between fluorescence intensity and the amount of SN-38 allowed quantitative determination of SN-38 in tumor tissues. Results clearly showed direct correlation between the amount of SN-38 in tumor sections and cancer cell death. Moreover, 3D reconstruction representing the distribution of SN-38 in tumors was obtained. Results from this study suggest the rationale for intratumoral drug administration and release of drugs inside tumor, which is necessary to design drug delivery systems with efficient antitumor activity.

HPLC analysis and extraction method of SN-38 in brain tumor model after injected by polymeric drug delivery system.

SN-38 is a highly potent anticancer drug but its poor solubility in aqueous solvent and adverse side effects limit clinical applications. To overcome these limitations, SN-38-loaded-injectable drug delivery depots have been intratumorally administered in xenograft tumor model in nude mice. The extraction and high performance liquid chromatography (HPLC) were performed in order to determine the amount of SN-38 inside tumors. SN-38 was extracted from tumors using DMSO. HPLC analysis was validated and resulted in linearity over the concentration range from 0.03 to 150 µg/mL (r(2) ≥ 0.998). Lower limit of detection (LLOD) and lower limit of quantitation (LLOQ) were 0.308 µg/mL and 1.02 µg/mL, respectively. The extraction efficiency (% recovery) of SN-38 in porcine tissues was similar to that of tumors which provided more than 90% recovery in all concentrations. Moreover, the variability of precision and accuracy within and between-day were less than 15%. Therefore, this extraction and HPLC protocol was applied to determine the amount of SN-38 in tumors. Results show higher remaining amount of SN-38 in tumor from SN-38-loaded polymeric depots than that of SN-38 solution. These results reveal that SN-38-loaded polymeric depots can prevent the leakage of free-drug out of tumors and can sustain higher level of SN-38 inside tumor. Thus, the therapeutic efficacy can be elevated by SN-38-loaded polymeric depots.

Preparation and in vitro characterization of SN-38-loaded, self-forming polymeric depots as an injectable drug delivery system.

This work describes the preparation and characterization of anticancer-loaded injectable polymeric depots that consisted of D,L-lactide (LA), ε-caprolactone (CL), and poly(ethylene glycol) (PEG) or [poly(ε-caprolactone)-random-poly(D,L-lactide)]-block-poly(ethylene glycol)-block-[poly(ε-caprolactone)-random-poly(D,L-lactide)] (PLEC) copolymers for malignant gliomas treatment. PLECs were polymerized with different percentages of LA to deliver 7-ethyl-10-hydroxycamptothecin (SN-38), a highly potent anticancer drug. SN-38-loaded depots could form directly in phosphate buffer saline with more than 98% encapsulation efficiency. The release rate of SN-38 from depots was found to depend on the amount of LA in PLECs, loading content of SN-38 in the depots, and depot weight. Encapsulation of SN-38 inside depots could enhance the stability of SN-38 where all of SN-38 released after 60 days was in an active form. Depots without SN-38 were evaluated as noncytotoxic against U-87MG, whereas SN-38-loaded depots showed cytotoxic effect as a function of concentration.

Preparation and biocompatibility study of in situ forming polymer implants in rat brains.

We describe the development of polymer implants that were designed to solidify once injected into rat brains. These implants comprised of glycofurol and copolymers of D: ,L: -lactide (LA), ε-caprolactone and poly(ethylene glycol) (PLECs). Scanning electron microscopy (SEM) and gel permeation chromatography (GPC) showed that the extent of implant degradation was increased with LA: content in copolymers. SEM analysis revealed the formation of porosity on implant surface as the degradation proceeds. PLEC with 19.3% mole of LA: was chosen to inject in rat brains at the volume of 10, 25 and 40 µl. Body weights, hematological and histopathological data of rats treated with implants were evaluated on day 3, 6, 14, 30 and 45 after the injection. Polymer solution at the injection volume of 10 µl were tolerated relatively well compared to those of 25 and 40 µl as confirmed by higher body weight and healing action (fibrosis tissue) 30 days after treatment. The results from this study suggest a possible application as drug delivery systems that can bypass the blood brain barrier.

SN-38:ß-cyclodextrin inclusion complex for in situ solidifying injectable polymer implants.

One of the most useful techniques to treat cancer is chemotherapy. However, anticancer drugs, such as SN-38, have limited solubility with strong side effects. This work aims to use SN-38:ß-cyclodextrin (ß-CD) inclusion complex for an injectable polymeric in situ forming implant containing poly(ethylene glycol) (PEG), poly(ε-caprolactone), and poly(D, L-lactide). It was found that implant formation and SN-38 encapsulation efficiency directly depended on weight ratio of SN-38 and ß-CD. At the ratio of SN-38:ß-CD of 1:7, the implant could not be formed perfectly and had lower encapsulation efficiency. Reduction of the amount of ß-CD to the ratio of 1:3 showed the higher encapsulation efficiency at 89.7 %. SN-38 release rate was also found to depend on ß-CD content and the implant weight. In addition, their active form was protected when encapsulated inside implants.