Pharmacy and Pharmaceutical Sciences Commons^™

In Vitro Comparative Study Of The Binding Affinity And Targeted-Drug Delivery Efficiency Of Egfr-Targeting Peptides, Jingda Wang

University of the Pacific Theses and Dissertations

Peptides have been used as targeting ligands in targeted drug delivery. Conjugating peptides to cytotoxicity agents via a linker to build peptide-drug conjugate (PDC) is a promising targeting strategy. The binding affinity of the peptide ligand and the receptor plays a crucial role in the PDC targeted drug delivery. Although the ligand binding which can be used in targeted drug delivery has been established conceptually, the quantitative or semi-quantitative contribution of binding affinity in targeting efficiency has not been fully explored. The optimal range of binding affinity of the peptide for targeted delivery remains unknown. Therefore, there is a lack …

Development Of Linked-Domain Protein Inhibitors Of The E2-Conjugating Enzyme Ube2d, Anneroos E. Nederstigt

University of the Pacific Theses and Dissertations

In most eukaryotic organisms, the ubiquitination pathway is one of the most important and versatile signaling systems in use. It is integral to processes such as protein degradation and homeostasis, DNA repair cell cycle regulation, signaling and regulation, epigenetics, and many more. Ubiquitin (Ub) is a short polypeptide of 8.6 kDa, 76 residues that functions as a reversible post-translation modification (PTM). It furthermore contains 7 different lysine residues (K6, K11, K27, K29, K33, K48, K63), all of which can form isopeptide linkages with one another to link individual Ub moieties to form unique polyUb chains onto substrates. The type of …

Bayesian-Derived Vancomycin Auc24h Threshold For Nephrotoxicity In Special Populations, Dan Ho

University of the Pacific Theses and Dissertations

A Bayesian-derived 24-hour area under the concentration-time curve over minimum inhibitory concentration from broth microdilution (AUC24h/MICBMD) ratio of 400 to 600 is recommended as the new monitoring parameter for vancomycin to optimize efficacy and minimize nephrotoxicity. The AUC24h threshold of 600 mg*h/L for nephrotoxicity was extrapolated from studies that assessed the general population. It is unclear if this upper threshold is consistent or varies when used in special populations such as critically ill patients, obese patients, patients with preexisting renal disease, and patients on concomitant nephrotoxins.The purpose of this study is to investigate the generalizability of the proposed vancomycin AUC24h …

Harnessing Transthyretin To Enhance The In Vivo Half-Life Of Human Interleukin-2 (Il-2), Fang Liu

University of the Pacific Theses and Dissertations

Protein therapeutics are available as cytokines, clotting factors, enzymes, hormones, growth factors, antibodies et al. They have been shown to be effective in treating a variety of important human diseases. Since human insulin was approved as the first recombinant protein therapeutic, this field has experienced rapid growth. One of the biggest challenges for protein therapeutics in clinical application is their short half-life. Except for monoclonal antibodies, which have serum half-life for weeks, most of the protein therapeutics have half-lives ranging from minutes to hours. Kidney filtration, proteasome degradation and liver metabolism are the main factors that attribute to their short …

Development Of Miriplatin-Loaded Nanoparticles Against Non-Small Cell Lung Cancer, Zhongyue Yuan

University of the Pacific Theses and Dissertations

Lung cancer claims the highest mortality and the second-most estimated new cases among all oncological diseases [1]. Non-small cell lung cancer (NSCLC) accounts for approximately 85% of all newly diagnosed lung cancers [2]. Approximately 40% of newly diagnosed lung cancer patients are stage IV. For stage IIIB/IV NSCLC, cytotoxic combination chemotherapy is standard first-line chemotherapy. A regimen of platinum (cisplatin or carboplatin) plus paclitaxel, gemcitabine, docetaxel, vinorelbine, irinotecan, or pemetrexed is the recommended clinical treatment [3].

Cisplatin is the first-generation platinum-based anti-cancer drug. Although cisplatin is much more effective than other platinum drugs at the same dosage [4], accumulating reports …

Impact Of 17-Beta Estradiol And Moderate-Intensity Exercise On Mesenteric Arterial Function Of Uc Davis Type-2 Diabetes Mellitus Rats, Md Rahatullah Razan

University of the Pacific Theses and Dissertations

The studies in this dissertation were designed to investigate the impacts of estrogen (17-β estradiol/E2) and moderate-intensity exercise (MIE) on the mesenteric arterial (MA) function of the University of California Davis type-2 diabetes mellitus (UCD-T2DM) Rat model. Our recent report suggests that diabetes impairs MA vasorelaxation in both sexes of the UCD-T2DM model. Particularly, we reported that MA from prediabetic male rats showed a greater impairment compared to that in prediabetic females. However, when females become diabetic, they exhibit a greater vascular dysfunction than males. Therefore, the aim of the first study was to investigate whether female sex hormone, specifically …

De Novo Prediction Of Drug–Target Interactions Using Laplacian Regularized Schatten P-Norm Minimization, Gaoyan Wu, Mengyun Yang, Yaohang Li, Jianxin Wang

Computer Science Faculty Publications

In pharmaceutical sciences, a crucial step of the drug discovery is the identification of drug–target interactions (DTIs). However, only a small portion of the DTIs have been experimentally validated. Moreover, it is an extremely laborious, expensive, and time-consuming procedure to capture new interactions between drugs and targets through traditional biochemical experiments. Therefore, designing computational methods for predicting potential interactions to guide the experimental verification is of practical significance, especially for de novo situation. In this article, we propose a new algorithm, namely Laplacian regularized Schatten p-norm minimization (LRSpNM), to predict potential target proteins for novel drugs and potential drugs for …

Development Of Asiatic Acid-Loaded Solid Lipid Nanoparticles For Nose To Brain Delivery: Ex Vivo And In Vivo Evaluation, Tissana Rojanaratha

Chulalongkorn University Theses and Dissertations (Chula ETD)

Asiatic acid (AA) has neuroprotective properties potential for prevention and treatment of Alzheimer’s disease. Natural waxes with various ratios of tween 80 and span 80 or soybean lecithin were formulated to obtain AA-loaded solid lipid nanoparticles (AA-SLN) in order to improve direct nose to brain transport. Optimal AA-SLN had particle size below 200 nm with uniform size distribution as confirmed by transmission electron microscope (TEM) results and zeta potential of nearly -30 mV indicating low risk on particle aggregation. Formulation with rice bran wax, tween80 and soybean lecithin (AA-RwS100) showed the highest drug content and entrapment efficiency of >98%. Differential …

Melanogenesis-Stimulating Isoflavonoids From Dalbergia Parviflora, Ponsawan Netcharoensirisuk

Chulalongkorn University Theses and Dissertations (Chula ETD)

Melanin, a cellular pigment, found in skin, hair and eyes is produced by melanocytes located at the basal layer of epidermis. Abnormal melanin production causes various pigmentation diseases. Low melanin content or dysfunction of melanogenesis not only decreases self-confidence and the quality of life but also enhances skin damage by external stimuli. Until now, there has been no reported remedy that possesses high efficacy and safety profile for hypopigmentation treatment in human. Development of novel darkening compounds from natural resources has recently become of an interest. In this study, the potent melanin-stimulating agents were screened from 45 compounds isolated from …

Study Of Self-Assembled Hyaluronic Acid Based Nanogel As Solubilization And Stabilization System For Asiatic Acid, Yu Yu Win

Chulalongkorn University Theses and Dissertations (Chula ETD)

Asiatic acid (AA), natural triterpene found in Centalla asiatica, possesses polypharmacological properties that can contribute to the treatment and prophylaxis of various diseases. However, its hydrophobic nature and rapid metabolic rate lead to poor bioavailability. The aim of this research is to study nanogel system from hyaluronic acid (HA) for solubilization and stability enhancement of AA. Poly(N-isopropylacrylamide) (pNIPAM) was conjugated onto HA using carbodiimide reaction followed by 1H NMR characterization. pNIPAM-grafted HA (HA-pNIPAM) nanogels were prepared with three concentrations of polymer, 0.1%, 0.15% and 0.25% w/v in water by sonication method. AA was loaded into the nanogel by incubation method. …

Development Of Tetrahydrocurcumin-Loaded Chitosan-Coated-Nanostructured Lipid Carriers For Topical Treatment Of Psoriasis, Hoang Thien Truong

Chulalongkorn University Theses and Dissertations (Chula ETD)

Chitosan (Ch)-coated nanostructured lipid carriers (NLCs) have great potential for topical delivery with high localization of chemotherapeutics. In this study, tetrahydrocurcumin (THC), a primary metabolite of curcumin with enhanced antioxidant and anticancer properties, was used as a model drug to prepare NLCs. Response surface methodology was employed to optimize THC-loaded Ch-coated NLCs (THC-Ch-NLCs) fabricated by high-shear homogenization. The optimized THC-Ch-NLCs had particle size of 244 ± 18 nm, zeta potential of -17.5 ± 0.5 mV, entrapment efficiency of 76.6 ± 0.2% and drug loading of 0.28 ± 0.01 mg/mL. In vitro release study of THC-Ch-NLCs showed sustained release following the …

Development Of Hek-293t Cells Stably Expressing The C-X-C Chemokine Receptor Type 4 (Cxcr4) For Binding Assay Of Potential Anti-Breast Cancer Agents, Thi Thai Ha Dinh

Chulalongkorn University Theses and Dissertations (Chula ETD)

The C-X-C chemokine receptor type 4 (CXCR4) has been recognized as a potential target in cancer drug discovery based on the high expression in cancer cells, particularly invasive breast cancer. This study aims to construct CXCR4-overexpressed cells to screen new anti-breast cancer agents targeting CXCR4 and identify the mediated target for anticancer effect. Firstly, five genetic isotypes of CXCR4, namely A, B, C, D and E, were amplified from Jurkat T cells. Amplicons of each CXCR4 isotype were ligated into cloning vectors and subcloned into expression vectors. They were transformed into competent Escherichia coli strain DH5-alpha cells. The presence of …

Spray Dried Asiatic Acid-Palm Oil Nanoemulsion With Improved Characteristics And Antihypertensive Effect Study In Rat Model Of Hypertension, Aditya Trias Pradana

Chulalongkorn University Theses and Dissertations (Chula ETD)

Hypertension is a risk factor for premature death worldwide.It is characterized by an increase in blood pressure, so it needs therapy to regulate it and keep the value normal. Asiatic acid (AA) and palm oil (PO) were alternative antihypertensive agents that were promising to be developed. Both were natural compounds obtained from the Centella asiatica and Elaesis guineensis plants. However, low solubility, low absorption, rapid metabolism, low bioavailability and high oxidation were the limitation for both of them as an active compounds. Thus, a combination of nanoemulsion formulation and drying with a spray dryer was necessary to improve the physicochemical …

Clinical Efficacy Of Silk Sericin Dressing With Collagen For Split-Thickness Skin Graft Donor Site Treatment, Apirujee Punjataewakupt

Chulalongkorn University Theses and Dissertations (Chula ETD)

Sericin dressing containing collagen hydrolysate (SDC) was evaluated in this study, consisting of two phases of clinical trials. The clinical safety of SDC was determined using a patch test in 103 healthy volunteers (phase I). Most of the results (around 90%) in the SDC group were interpreted as negative and doubtful reactions, and the remaining results (around 10%) were weak reactions. After that, the clinical efficacy and safety of SDC were investigated in 21 patients with 30 split-thickness skin graft (STSG) donor sites (phase II). Each donor site was divided into two equal sites. SDC or the commercial dressing (Bactigras®) …

Production Optimization Of Porcine Reproductive And Respiratory Syndrome (Prrs) Virus Nucleocapsid Protein In Nicotiana Benthamiana, Boonyasit Porngarm

Chulalongkorn University Theses and Dissertations (Chula ETD)

Porcine Reproductive and Respiratory Syndrome virus (PRRSV) is a considerable pathogen to occur disease in pigs and effect to economic on the swine industry around the world including Thailand. Routine observation, rapid diagnosis of PRRSV infection is essential for effective monitoring and disease control. The serological assays using highly conserved viral nucleocapsid (N) protein are widely used for the detection of antibodies to the PRRSV. Accordingly, this study was aimed to produce the N-protein of the PRRSV in the plant system by using Nicotiana benthamiana. The N-protein gene was designed into four constructs that contained with and without the plant …

Antioxidant Activity Of Thunbergia Laurifolia Lindl. Ethanolic Extract In Keratinocytes, Buakotchaphan Jirabanjerdsiri

Chulalongkorn University Theses and Dissertations (Chula ETD)

Fine particulate matter (PM2.5) can cause skin damage through the induction of oxidative stress in epidermis. Antioxidants help counteract with cellular oxidant species and maintain cell homeostasis. This study aims to examine the protective effect of Thunbergia laurifolia lindl. ethanolic extract on PM2.5-mediated oxidative stress in epidermal keratinocytes. High-performance liquid chromatography with diode array detection was conducted for quantitative analysis of rosmarinic acid content in the extract. Cell viability was detected by the 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide assay. Intracellular ROS was monitored using 2’,7’-Dichlorodihydrofluorescein diacetate. Proteins related to p62-Keap1-Nrf2 signaling pathway were examined by western blot analysis. Expressions of Nrf2 and p62 …

Antioxidant With Antimelanogenic Activities Of Sericin Hydrolysates Optimized By Response Surface Methodology In Human Melanin-Generating Mnt-1 Cells, Keerati Joyjamras

Chulalongkorn University Theses and Dissertations (Chula ETD)

Sericin, a protein presenting in the wastewater from silk industry, causes water pollution and ecological problem. To increase economic value to this waste product, the optimum enzymatic condition that could create sericin hydrolysates with high antioxidant and antimelanogenic capacities was generated through response surface methodology (RSM). Response surface plots demonstrate the major role of temperature on scavenging capacity of sericin hydrolysates assessed via DPPH, FRAP and ORAC assays. Alcalase®-hydrolyzed sericin consisted of sericin-related peptides in differing amounts and smaller sizes compared with unhydrolyzed sericin, as respectively demonstrated by peptidomic and SDS-PAGE analysis. Pre-incubation with 20 mg/mL sericin hydrolysates digested by …

Development Of Plant-Produced Subunit Vaccine And Therapeutic Protein For Covid-19, Konlavat Siriwattananon

Chulalongkorn University Theses and Dissertations (Chula ETD)

Due to the rapid transmission of the Coronavirus Disease 2019 (COVID-19) causing serious public health problems and economic burden, the development of effective therapeutic interventions is urgently needed for controlling the ongoing pandemic disease. In this study, we have transiently produced recombinant SARS-CoV-2 RBD and human ACE2 fused with the Fc region of human IgG1 in Nicotiana benthamianain in order to use as a preventive subunit vaccine and therapeutic against SARS-CoV-2. The recombinant SARS-CoV-2 RBD-Fc subunit vaccine was formulated with different commercially available adjuvants including aluminium hydroxide gel (Alum), AddaVaxTM (MF59), monophosphoryl lipid A from Salmonella Minnesota R595 (mPLA-SM), and …

Taxonomy And Biological Activities Of A Novel Saccharothrix Species From Soil Of Sichang Island, Md Abul Kalam Azad

Chulalongkorn University Theses and Dissertations (Chula ETD)

Actinobacteria are the sources of bioactive natural products. Rare actinobacteria are the less frequently isolated genera of actinobacteria. During an investigation of diversity of rare actinobacteria, actinobacteria isolate SC076T was isolated from a soil sample collected from Sichang Island, Chonburi Province, Thailand. The strain showed the highest 16S rRNA gene similarity to Saccharothrix australiensis DSM 43800T (98.58%) and Saccharothrix espanaensis DSM 44229T (98.58%). The zigzag morphology of the spore chain was observed on the aerial mycelia. meso-diaminopimelic acid was detected in the peptidoglycan. Whole-cell sugars contained rhamnose, ribose, mannose glucose and galactose. Polar lipids are phosphatidylethanolamine, hydroxyphosphatidylethanolamine, diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol …

Effect Of Hydroquinone 5-O-Cinnamoyl Ester Of Renieramycin M On The Suppression Of Lung Cancer Stem Cells, Nattamon Hongwiangchan

Chulalongkorn University Theses and Dissertations (Chula ETD)

Cancer stem cells (CSCs) are distinct cancer populations with tumorigenic and self-renewal abilities. CSCs are drivers of cancer initiation, progression, therapeutic failure, and disease recurrence. Thereby, novel compounds targeting CSCs offer a promising way to control cancer. In this study, the hydroquinone 5-O-cinnamoyl ester of renieramycin M (CIN-RM) was demonstrated to suppress lung cancer CSCs. CIN-RM was toxic to lung cancer cells with a half-maximal inhibitory concentration around 15 µM. CIN-RM suppressed CSCs by inhibiting colony and tumor spheroid formation. In addition, the CSC population was isolated and treated and the CSCs were dispatched in response to CIN-RM within 24 …

Α-Glucosidase Inhibitors From Dendrobium Delacourii, Dendrobium Gibsonii And Aerides Multiflora, May Thazin Thant

Chulalongkorn University Theses and Dissertations (Chula ETD)

In this study, three plants from the Orchidaceae family, i.e., Dendrobium delacourii, Dendrobium gibsonii, and Aerides multiflora, were investigated for their chemical constituents and α-glucosidase inhibitory activities. A total of thirty compounds were isolated and structurally characterized. Eleven known compounds were identified from Dendrobium delacourii, including hircinol, ephemeranthoquinone, densiflorol B, moscatin, 4,9-dimethoxy-2,5-phenanthrenediol, gigantol, batatasin III, lusianthridin, 4,4',7,7'-tetrahydroxy-2,2'-dimethoxy-9,9',10,10'-tetrahydro-1,1'-biphenanthrene, phoyunnanin E, and phoyunnanin C. Two new compounds, i.e., dihydrodengibsinin and dendrogibsol, were isolated from Dendrobium gibsonii, along with seven known compounds including ephemeranthol A, dengibsinin, nobilone, aloifol I, lusianthridin, denchrysan A, and 4-methoxy-9H-fluorene-2,5,9-triol. Four new compounds, i.e., aerimultins A-C and dihydrosinapyl dihydroferulate, …

Lipase Inhibitors From Dendrobium Senile, Myat Pann Phyu

Chulalongkorn University Theses and Dissertations (Chula ETD)

Obesity is characterized as an abnormal lipid metabolism due the imbalance between the energy intake and output. Pancreatic lipase is secreted by the pancreas and plays an important role in the digestion and absorption of lipids in the small intestine. Inhibition of pancreatic lipase enzyme can reduce dietary fat absorption which will lead to loss of weight and finally result in hypocholesterolemia and hypoglycemia. From the whole plant of Dendrobium senile, a new phenanthrene derivative was isolated, together with seven known compounds, including 2,5,7-trihydroxy-4-methoxyphenanthrene (1), moscatin (2), 2,5-dihydroxy-4,9-dimethoxyphenanthrene (3), moscatilin (4), aloifol I (5), 4,4ʹ,8,8ʹ-tetramethoxy[1,1ʹ-biphenanthrene]-2,2ʹ,7,7ʹ-tetrol (6), 2,2ʹ,7,7ʹ-tetrahydroxy-4,4ʹ-dimethoxy-1,1ʹ-biphenanthrene (7) and bleformin …

Identification, Antifungal And Plant Growth Promoting Activities Of Endophytic Actinomycetes From Orchids, Nisachon Tedsree

Chulalongkorn University Theses and Dissertations (Chula ETD)

Sixty-two endophytic actinomycetes were isolated from 15 Thai orchids. They were identified as Streptomyces (34 isolates), Micromonospora (21 isolate), Streptosporangium (2 isolates), Actinomadura (1 isolates), Amycolatopsis (3 isolates) and Pseudonocardia (1 isolates) based on their phenotypic, chemotaxonomic and genotypic characteristics. The antimicrobial activity screening revealed that Streptomyces (18 isolates), Micromonospora (12 isolates) and Streptosporangium (1 isolate) exhibited antimicrobial activity against Bacillus subtilis ATCC 6633, Kocuria rhizophila ATCC 9341, Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853 and Candida albicans ATCC 10231. Strain DR2-2 could inhibit all tested pathogens. Based on 16S rRNA gene sequencing, strain DR6-1 …

Extraction Of Cannabinoids Using Vegetable Oils And Its Uva-Photoprotective Effect On Human Skin Keratinocytes, Nur Alfan Muhammad Zen

Chulalongkorn University Theses and Dissertations (Chula ETD)

Nowadays, vegetable oil has attracted attention in its role as an alternative solvent. Its ability to dissolve various active compounds from plants has been proven by several previous studies. Moreover, other benefits of the use of vegetable oil as a solvent are affordable, non-toxic, and eco-friendly. The extraction process is one of the crucial factors that affect the quality of cannabis. Ethanol is still consistently the best solvent for cannabis extraction in terms of yield production compared to other organic solvents used in this study including oil whose yield cannot be calculated since vegetable oil cannot be evaporated. HPTLC fingerprint …

Production And Characterization Of Escherichia Coli Outer Membrane Vesicles Displaying Anti-Muc1 Single-Chain Variable Fragment Via Spytag/Spycatcher System, Sedthawut Laotee

Chulalongkorn University Theses and Dissertations (Chula ETD)

Outer membrane vesicles (OMVs) secreted from Gram-negative bacteria have been discovered for a decade. Special features like high stability, ease of production, and intrinsic adjuvanticity highlight the use of OMVs in diverse applications such as vaccination, bioimaging, and multifunctional delivery systems. Synthetic biological approaches can functionalize OMVs to present heterologous proteins by expressing genetic fusion of target protein to outer membrane proteins. However, complex proteins cannot be incorporated into the OMVs due to lack of some post-translational modifications in bacteria. Herein, we demonstrated a convenient method for presentation of versatile proteins in OMVs with the implementation of the bio-ligation system …

3,4-Dihydroxy-5,4’-Dimethoxybibenzyl Sensitizes Non-Small Cell Lung Cancer Cells To Cisplatin-Induced Apoptosis Via P53 Upregulation, Hardyanti Eka Putri

Chulalongkorn University Theses and Dissertations (Chula ETD)

Lung cancer is a leading fatal malignancy with the highest number of cancer deaths. Targeting a specific protein regulating cancer progression and metastasis has been attracting much attention for the development of cancer therapy. Thus, this study was aimed to investigate the effect of 3,4-dihydroxy-5,4′-dimethoxybibenzyl (DS-1) in targeting MDM2-attenuating p53 function and inhibition EMT in lung cancer cells. The efficacy of DS-1 or combined with cisplatin in lung cancer cells was determined by MTT, nuclear staining, and Annexin V/PI assays. The expression of apoptosis- and EMT-related proteins was determined by western blot analysis. Metastatic behaviors were evaluated by cell shape …

Effectiveness Of A Pharmacist-Led Expert System For Medication Adherence And Blood Pressure Control Of Adults With Hypertension In The Philippines: A Randomized Controlled Trial, Margarita Gutierrez

Chulalongkorn University Theses and Dissertations (Chula ETD)

In the Philippines, the Hypertension control rate is only 20% due to low medication adherence. The author proposes an intervention to supplement government program. The aim of the study is to assess the effect on medication adherence and blood pressure control of patients. A randomized control trial was conducted at ten study sites in Region IV-A of the Philippines between May 2021 and January 2022. Outcomes are measured at enrollment as well as at three different time intervals. A total of 417 patients were eligible for the study with 203 in the control group and 214 in the intervention group. …

Assessment Of Pharmacovigilance System Of New Drugs In Thailand, Nisittra Polkot

Chulalongkorn University Theses and Dissertations (Chula ETD)

Previous studies evaluated pharmacovigilance (PV) system in term of passive surveillance in only post-marketing phase and did not specify new drugs. None study reviewed PV system of new drugs from pre-marketing phase to post-marketing phase. In addition, the situation of new safety monitoring program (SMP) risk-based approach integrated with risk management plan (RMP) was unknown. The objectives of the study were to review pharmacovigilance system of new drugs in targeted countries and to assess pharmacovigilance system of new drugs in Thailand. Method of the first objective was systematic review and primary data sources were drug regulatory authority websites in 83 …

Antivenom Cross-Neutralization And Neutralization: A Systematic Review Of Non-Clinical Studies In Asia Region, Sutinee Soopairin

Chulalongkorn University Theses and Dissertations (Chula ETD)

Background: Cross-neutralizing strategy has been applied to improve access to antivenoms which is a key to reduce mortality and disability of snakebite envenoming. However, preclinical studies have been conducted to discover antivenom’s cross-neutralizing ability when clinical studies may not be ethically applicable. This study aimed to identify and summarize scattered evidence regarding Asia antivenom’s preclinical efficacy. Methods: We performed a systematic review to search for articles published up to May 30, 2022, in PubMed, Scopus, Web of Science, and Embase. Reference searching of eligible articles was done. Preclinical studies reported the available Asia antivenom’s neutralizing ability against Asia snake lethality …

การพัฒนาเจลก่อตัวเองของยาด็อกซีไซคลินสำหรับรักษาโรคปริทันต์อักเสบ, สิริกาญจน์ หิรัญธนวิวัฒนา

Chulalongkorn University Theses and Dissertations (Chula ETD)

โรคปริทันต์อักเสบเป็นโรคในช่องปากชนิดหนึ่งที่พบมากในปัจจุบัน ซึ่งเป็นภาวะการอักเสบของเหงือกที่เกิดการทำลายเนื้อเยื่อโดยรอบที่รองรับฟัน ยาด็อกซีไซคลิน ไฮเคลต (doxycycline hyclate; DH) นิยมใช้กันอย่างแพร่หลายสำหรับการรักษาโรคติดเชื้อแบคทีเรียรวมถึงการรักษาโรคปริทันต์อักเสบ ปัจจุบันระบบเจลก่อตัวเอง (in situ forming gel system) เป็นระบบการนำส่งยาที่ได้รับความสนใจเพิ่มมากขึ้นสำหรับการนำส่งยาในช่องปาก โดยเป็นระบบนำส่งในรูปแบบของสารละลายแต่เมื่อสัมผัสกับร่างกายจะสามารถเปลี่ยนสถานะจากสารละลายกลายเป็นเจลได้โดยขึ้นกับปัจจัยทางสภาพแวดล้อม จุดประสงค์ของการศึกษานี้คือการพัฒนาเจลก่อตัวเองของยา DH ให้มีการปลดปล่อยยาอย่างต่อเนื่อง โดยเตรียมสูตรตำรับเจลก่อตัวเอง 15 สูตร ซึ่งประกอบด้วย poloxamer407; P407 (16%w/w), poloxamer188; P188 (0, 1, 2.5, 5, 10%w/w) และ hydroxypropyl methylcellulose; HPMC (0, 0.2, 0.5%w/w) ด้วยวิธีร้อนและเย็น แล้วทำการศึกษาลักษณะทางเคมีกายภาพ ปริมาณยา คุณสมบัติการยึดติดเยื่อเมือก ความหนืด ความคงตัว และการปลดปล่อยตัวยาของสูตรตำรับ พบว่าสูตรตำรับเจลก่อตัวเองทั้งหมดแสดงลักษณทางเคมีกายภาพเป็นสารละลายสีเหลืองใส มีค่า pH อยู่ในช่วง 6.45-6.81 ระบบเจลก่อตัวเองของยา DH ที่ได้รับการพัฒนาโดยมีส่วนผสมของ P407 16% w/w, P188 5% w/w และ HPMC 0.5%w/w (F14) แสดงอุณหภูมิการเกิดเจลที่ 35±0.57°ซ และการคงอยู่ของตัวยาบน semipermeable membrane ที่เคลือบด้วย mucin ได้ร้อยละ 43.51±0.003 โดยมีลักษณะการปลดปล่อยอย่างต่อเนื่องเป็นเวลานาน 24 ชั่วโมง และพบว่าที่อุณหภูมิ 37°ซ สูตรตำรับมีความหนืดเพิ่มขึ้นอย่างมีนัยสำคัญทางสถิติ (p<0.05) อย่างไรก็ตาม ตำรับที่พัฒนาขึ้นเกิดการเปลี่ยนสีเมื่อเวลาผ่านไปและเมื่อเก็บไว้ที่อุณหภูมิสูง จึงควรมีการพัฒนาสูตรตำรับเพิ่มเติมต่อไปเพื่อให้มีความคงตัวดียิ่งขึ้น