Sodium carboxymethylcellulose (SCMC) is widely used in the design of wound dressing owing to its high water bonding capacity, good compatibility with skin and mucous membrane, biocompatibility and abundant availability at a low cost. This study aims to design drug-free (low (LV), medium (MV) and high molecular weight (HV)) SCMC scaffolds and promote their ability to promote partial thickness burn wound healing via wound moist regulation and microbial burden control. In addition, SCMC scaffolds of distinct wound healing ability is incorporated with γ-tocotrienol as antioxidant therapeutic and has its wound healing property assessed against pure tocopherol and tocotrienol. SCMC scaffolds were prepared by means of solvent evaporation technique and their physicochemical properties namely, in vitro erosion, moisture affinity, morphology, tensile strength, polymer molecular weight and carboxymethyl substitution were investigated against partial thickness burn wound

Ramli, Nor Amlizan

UiTM Institutional Repository (Univ. Teknologi MARA)

I n s t i t u t e  o f  G r a d u a t e  S t u d i e s  ( I G S )* (MS) = Main Supervisor       (CS) = Co Supervisor24313233Faculty of PharmacySodium carboxymethylcellulose (SCMC) is widely used in the design of wound dressing owing to its high water bonding capacity, good compatibility with skin and mucous membrane, biocompatibility and abundant availability at a low cost. This study aims to design drug-free (low (LV), medium (MV) and high molecular weight (HV)) SCMC scaffolds and promote their ability to promote partial thickness burn wound healing via wound moist regulation and microbial burden control. In addition, SCMC scaffolds of distinct wound healing ability is incorporated with γ-tocotrienol as antioxidant therapeutic and has its wound healing property assessed against pure tocopherol and tocotrienol.  SCMC scaffolds were prepared by means of  solvent evaporation technique and their physicochemical properties namely, in vitro erosion, moisture affinity, morphology, tensile strength, polymer molecular weight and carboxymethyl substitution were investigated against partial thickness burn wound. The transepidermal water loss (TEWL) from wound of rats treated by control > HV scaffold > LV – MV scaffold. HV scaffold possessed the highest tensile strength of all matrices and was resistant to erosion in simulated wound fluid. In spite of constituting small nanopores, it afforded a substantial TEWL than MV and LV scaffolds from wound across an intact matrix through its low Pectin has received a widespread application in oral drug delivery system design due to its biodegradability, biocompatibility and non-toxicity. This study aims to formulate sustained-release pectinate beads with diclofenac sodium as small molecule drug model by means of microwave technology and pectinate nanoparticles with insulin as macromolecular drug. The pectinate beads were prepared by an extrusion method with chitosan loading internally in the pectinate beads or externally via coacervation. These beads were treated by microwave at 80 W for 5, 10, 21 and 40 min, and had their drug release examined against physicochemical changes of matrices. Treatment of pectinate beads by microwave did not lead to a decrease, but an increase in the extent of drug released at 4 h of dissolution. The drug release of pectinate beads was reduced only upon core loading of chitosan on treating the externally coacervated pectinate-chitosonium beads with microwave. The treatment of chitosan–pectinate matrix by microwave brought about an increase in the extent of drug released unlike those of pectinate–chitosonium beads. Apparently, the loading of chitosan into the interior of pectinate matrix could effectively The influence of novel triacylglycerols (TAGs) on the topical delivery of α-tocopherol and their role as emollients was investigated. For topical application, TAGs as enhancers were developed to improve the delivery of actives across the skin as the skin barrier limited their use. Medium chain triacylglycerols (MCTs) have previously been used as carriers and enhancers for fat soluble vitamins and other actives as they work efficiently in delivering the active through the skin by modifying properties of the stratum corneum (SC) barrier. However, little published data are available concerning the permeation and effects of MCTs following topical application. The first part of the study was aimed to: i) develop and validate an assay method for determining α-tocopherol in methanolic solution and rat skin extract; ii) develop and validate an assay method for determining fatty acids methyl esters using gas chromatography; and iii) validate the automated diffusion equipment for in vitro experiment. The second part of the study was to produce novel TAGs namely structured virgin coconut oil (SVCO), by lipase catalysed acidolysis of caprylic acid and the virgin coconut oil (VCO). The percentage of caprylic acid finally incorporated Name :Nor Amlizan RamliTitle :Carboxymethylcellulose Scaffolds For Treatment Of Partial Thickness Burn Wound - The Aspects Of Wound Moist Regulation, Bacterial Burden Control And Tocotrienol TherapeuticSupervisor : Associate Prof. Dr. Wong Tin Wui  (MS)Name :Nurjaya SumiranTitle :Pectinate Micro-And Nano-Matrices As Small Molecule And Protein Drug CarrierSupervisor : Associate Prof. Dr. Wong Tin Wui  (MS)Dr. Ibtisam Abdul Wahab (CS)Name :Salizatul Ilyana IbrahimTitle :Structured Lipids From Virgin Coconut Oil As Permeation Enhancers And Emollients In CosmeticsSupervisor : Prof. Dato’ Dr. Abu Bakar Abdul Majeed (MS)Associate Prof. Dr. Mamot Said (CS)L e a d i n g  Y o u  T o  G r e a t e r  H e i g h t s ,  D e g r e e  b y  D e g r e e 25moisture affinity characteristics. HV scaffold was also found to protect moisture loss with minimal accumulation at wound bed thus promoted reepithelialisation process. Transepidermal water movement  wound healing by scaffolds was governed by SCMC molecular weight instead of its carboxymethyl substitution degree or matrix pore size distribution. In infected partial thickness wound, in vitro polymer characteristics, microstructure, gelling, bioadhesiveness, microbial inhibitory, in vivo microbe-colonized wound healing, microbe removal and infection control properties were examined against Gram positive Staphylococcus aureus and Gram negative Pseudomonas aeruginosa. P. aeruginosa was removed via gelling action of LV scaffold which encapsulated microbes possibly with the binding aid of their extracellular by-product. S. aureus  was removed via HV scaffolds ability to crease into multiple tight folds to accommodate the microbes under compression and retarded its growth. SCMC scaffolds promoted healing via physical attachment and retard the drug release without subjecting the beads to the treatment of microwave. The microwave was merely essential to reduce the release of drug from pectinate beads when the chitosan was introduced to the pectinate matrix by means of coacervation. The calcium pectinate-insulin nanoparticles were prepared by ionotropic gelation method, with alginate, sodium chloride or Tween 80 as additive. Their in vitro physicochemical, drug release and in vivo blood glucose lowering characteristics were evaluated. Spherical calcium pectinate-insulin nanoparticles were characterized by size, zeta potential, insulin content and insulin association efficiency of 348.4 ± 12.9 nm, −17.9 ± 0.8 mV, 8.4 ± 1.0% and 63.8 ± 7.4%, respectively. They released less than 25% insulin following 24 h in simulated intestinal medium and exhibited delayed blood glucose lowering effect in rats. Incorporation of solubilizer sodium chloride or Tween 80 into nanoparticles in the reaction products was optimized using the central composite design (CCD). It was suggested that the highest incorporation of caprylic acid (68.07%) would be achieved by: caprylic acid to VCO ratio of 1.70 (w/w); an enzyme load of 22.60%; at 63.4°C; a water content of 3.53%; and at 96 h. Using the predicted optimum conditions, pentaplicate experiments gave a good result (64.11 ± 1.14%) that coincided with the predicted value and the model was deemed to be adequate. The third part of the study looked at the effect of permeation enhancer formulations on the permeation of α-tocopherol, a model permeant, in vitro and in vivo. Both approaches revealed that SVCO was a significantly better permeation enhancer than VCO. This probably indicated that the shorter carbon chain SVCO might be a better permeation enhancer. The final part of the study investigated the emollient properties of the newly develop enhancers. These were determined using removal from wound bed which was generally aided via high polymeric carboxymethyl substitution degree and subseqeuent increased of bioadhesive property of the scaffolds. The HV-PVP scaffolds served as the vehicle of γ-tocotrienol. The vitamin incorporation was characterised by drug content of 91.238 ± 0.137 %. The instantaneous vitamin release from the carrier may affect the initial wound healing process as bi-mechanisms of modulating the transepidermal water loss contributed by the HV-PVP carrier and antioxidant activity of  γ-tocotrienol. The used of HV-PVP scaffold as the carrier for γ-tocotrienol deemed to optimize its delivery to the wounded area and showed promising outcome in wound healing process.did not enhance blood glucose lowering capacity owing to sodium chloride reduced matrix insulin content and Tween 80 interacted with water and had its blood glucose dilution effect negated. Combination of nanoparticles with alginate gel to allow prolonged intestinal residence and more insulin release did not enhance their blood glucose lowering capacity because of calcium alginate-cross-linked gel formation that could retard insulin release and migration into systemic circulation. Physicochemical responses of additives in vivo affected blood glucose regulation property of pectin-insulin nanoparticles.instrumental measurement and sensorial perspective by trained panels. Skin biophysical studies on various skin parameters such as moisture and transepidermal water loss (TEWL) contents, skin firmness and elasticity and surface evaluation on the living skin (SELS) from topical application to human healthy volunteers showed statistically significantly improved effects by both SVCO creams and VCO creams compared to the skin before creams application. In conclusion, novel permeation enhancers were successfully developed by acidolysis of VCO and caprylic acid. The SVCO was found to exert better skin permeation enhancing effect on α-tocopherol than VCO. Both VCO and SVCO gave emolliency effect when applied topically

Carboxymethylcellulose scaffolds for treatment of partial thickness burn wound - the aspects of wound moist regulation, bacterial burden control and tocotrienol therapeutic / Nor Amlizan Ramli

Sodium carboxymethylcellulose (SCMC) is widely used in the design of wound dressing owing to its high water bonding capacity, good compatibility with skin and mucous membrane, biocompatibility and abundant availability at a low cost. This study aims to design drug-free (low (LV), medium (MV) and high molecular weight (HV)) SCMC scaffolds and promote their ability to promote partial thickness bum wound healing via wound moist regulation and microbial burden control. In addition, SCMC scaffolds of distinct wound healing ability is incorporated with γ-tocotrienol as antioxidant therapeutic and has its wound healing property assessed against pure tocopherol and tocotrienol. SCMC scaffolds were prepared by means of solvent evaporation technique and their physicochemical properties namely, in vitro erosion, moisture affinity, morphology, tensile strength, polymer molecular weight and carboxymethyl substitution were investigated against partial thickness bum wound. The transepidermal water loss (TEWL) from wound of rats treated by control > HV scaffold > LV - MV scaffold. HV scaffold possessed the highest tensile strength of all matrices and was resistant to erosion in simulated wound fluid. In spite of constituting small nanopores, it afforded a substantial TEWL than MV and LV scaffolds from wound across an intact matrix through its low moisture affinity characteristics. HV scaffold was also found to protect moisture loss with minimal accumulation at wound bed thus promoted reepithelialisation process. Transepidermal water movement wound healing by scaffolds was governed by SCMC molecular weight instead of its carboxymethyl substitution degree or matrix pore size distribution. In infected partial thickness wound, in vitro polymer characteristics, microstructure, gelling, bioadhesiveness, microbial inhibitory, in vivo microbe-colonized wound healing, microbe removal and infection control properties were examined against Gram positive Staphylococcus aureus and Gram negative Pseudomonas aeruginosa. P. aeruginosa was removed via gelling action of LV scaffold which encapsulated microbes possibly with the binding aid of their extracellular by-product. S. aureus was removed via HV scaffolds ability to crease into multiple tight folds to accommodate the microbes under compression and retarded its growth. SCMC scaffolds promoted healing via physical attachment and removal from wound bed which was generally aided via high polymeric carboxymethyl substitution degree and subseqeuent increased of bioadhesive property of the scaffolds. The HV-PVP scaffolds served as the vehicle of γ-tocotrienol. The vitamin incorporation was characterised by drug content of 91.238 ± 0.137 %. The instantaneous vitamin release from the carrier may affect the initial wound healing process as bi-mechanisms of modulating the transepidermal water loss contributed by the HV-PVP carrier and antioxidant activity of y-tocotrienol. The used of HV-PVP scaffold as the carrier for γ-tocotrienol deemed to optimize its delivery to the wounded area and showed promising outcome in wound healing process

UNIVERSITI TEKNOLOGI MARACARBOXYMETHYLCELLULOSE SCAFFOLDS FOR TREATMENT OF PARTIAL THICKNESS BURN WOUND - THE ASPECTS OF WOUND MOIST REGULATION, BACTERIAL BURDEN CONTROL AND TOCOTRIENOL THERAPEUTICNOR AMLIZAN RAMLIThesis submitted in fulfillment of the requirements for the degree of Doctor of PhilosophyFaculty of PharmacySeptember 2014AUTHOR’S DECLARATIONI declare that the work in this thesis was carried out in accordance with the regulation of Universiti Teknologi MARA. It is original and is the result of my own work, unless otherwise indicated or acknowledged as referenced work. This topic has not been submitted to any other academic institution or non-academic institution for any other degree or qualification.I, hereby, acknowledge that I have been supplied with the Academic Rules and Regulations for Post Graduate, Universiti Teknologi MARA, regulating the conduct of my study and research.Name o f Student : Nor Amlizan RamliStudent I.D. No. : 2006209044Programme : Doctor o f Philosophy (PH990)Faculty : PharmacyThesis Title Carboxymethylcellulose scaffolds for treatment ofpartial thickness wound - The aspects of wound moist regulation, bacterial burden control andSignature o f StudentDate September 2014ABSTRACTSodium carboxymethylcellulose (SCMC) is widely used in the design o f wound dressing owing to its high water bonding capacity, good compatibility with skin and mucous membrane, biocompatibility and abundant availability at a low cost. This study aims to design drug-free (low (LV), medium (MV) and high molecular weight (HV)) SCMC scaffolds and promote their ability to promote partial thickness bum wound healing via wound moist regulation and microbial burden control. In addition, SCMC scaffolds o f distinct wound healing ability is incorporated with y-tocotrienol as antioxidant therapeutic and has its wound healing property assessed against pure tocopherol and tocotrienol. SCMC scaffolds were prepared by means o f solvent evaporation technique and their physicochemical properties namely, in vitro erosion, moisture affinity, morphology, tensile strength, polymer molecular weight and carboxymethyl substitution were investigated against partial thickness bum wound. The transepidermal water loss (TEWL) from wound o f rats treated by control > HV scaffold > LV -  MV scaffold. HV scaffold possessed the highest tensile strength of all matrices and was resistant to erosion in simulated wound fluid. In spite of constituting small nanopores, it afforded a substantial TEWL than MV and LV scaffolds from wound across an intact matrix through its low moisture affinity characteristics. HV scaffold was also found to protect moisture loss with minimal accumulation at wound bed thus promoted reepithelialisation process. Transepidermal water movement wound healing by scaffolds was governed by SCMC molecular weight instead o f its carboxymethyl substitution degree or matrix pore size distribution. In infected partial thickness wound, in vitro polymer characteristics, microstructure, gelling, bioadhesiveness, microbial inhibitory, in vivo microbe-colonized wound healing, microbe removal and infection control properties were examined against Gram positive Staphylococcus aureus and Gram negative Pseudomonas aeruginosa. P. aeruginosa was removed via gelling action of LV scaffold which encapsulated microbes possibly with the binding aid of their extracellular by-product. S. aureus was removed via HV scaffolds ability to crease into multiple tight folds to accommodate the microbes under compression and retarded its growth. SCMC scaffolds promoted healing via physical attachment and removal from wound bed which was generally aided via high polymeric carboxymethyl substitution degree and subseqeuent increased o f bioadhesive property of the scaffolds. The HV-PVP scaffolds served as the vehicle of y-tocotrienol. The vitamin incorporation was characterised by drug content of 91.238 ± 0.137 %. The instantaneous vitamin release from the carrier may affect the initial wound healing process as bi-mechanisms of modulating the transepidermal water loss contributed by the HV-PVP carrier and antioxidant activity of y-tocotrienol. The used of HV-PVP scaffold as the carrier for y-tocotrienol deemed to optimize its delivery to the wounded area and showed promising outcome in wound healing process.TABLE OF CONTENTSCONFIRMATION BY PANEL OF EXAMINERSPageiiAUTHOR’S DECLARATION iiiABSTRACT ivACKNOWLEDGEMENT VTABLE OF CONTENTS viLIST OF TABLES xiLIST OF FIGURES xiiLIST OF SYMBOL xivLIST OF ABBREVIATIONS xviiCHAPTER ONE: INTRODUCTION 11.1 Overview 11.1.1 Wound 11.1.2 Wound Healing 11.1.3 Wound Dressing 31.2 Problem Statement 31.3 Objectives o f Study 51.4 Scope o f Study 51.5 Organisation o f Thesis 6CHAPTER TWO: LITERATURE REVIEW 72.1 Introduction 72.2 Physiology o f Skin 72.2.1 Epidermis 82.2.2 Dermis 92.3 Skin wound 9viCHAPTER ONE INTRODUCTION1.1 OVERVIEW1.1.1 WoundWound is defined as an injury with disruption of the normal continuity o f the body structures [1]. There are several types of wounds: contused wound, incised wound, lacerated wound, open wound, penetrating wound, perforating wound, puncture wound and bum wound. Wounds can be classified as chronic as well as acute wounds. The causes o f wound injury include: 1) physical agents such as trauma, extremes of temperatures, radiation and electric shock and 2) chemical agents such as asbestos, carbon monoxide and insecticides [2].Acute wound refers to injury which occurs secondary to surgery or trauma in an individual [3]. It is characterised by a fast healing rate with complete recovery of the injury. Chronic wound is affected by factors which bring about disruption to the normal, controlled inflammatory phase or cellular proliferative phase o f an injury that may delay the healing process [3, 4], It can be defined as a loss in tissue integrity produced through frequent recurrence and/or over an extended duration. Pressure ulcer, diabetic ulcer, lower leg ulcer, vascular ulcer, post-operative open wound, and entero-cutaneous fistulae are the common examples of chronic wounds [5]. These types of wound are approached differently in terms o f treatment to optimise the healing process.1.1.2 Wound HealingWound is characterized by skin losses its physical integrity thus exposing the tissue to the immediate environment with an excessive loss of water [4, 6, 7]. Wound healing is a prompt response that preserves and maintains the integrity o f an organ suffering tissue loss. It is a dynamic process which encompasses three overlapping phases namely inflammation, proliferation and remodeling (Figure 1.1). These sequential phases originate from the interaction and responses of cells in parallel with1

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Carboxymethylcellulose scaffolds for treatment of partial thickness burn wound - the aspects of wound moist regulation, bacterial burden control and tocotrienol therapeutic / Nor Amlizan Ramli

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