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Biomedical subjects

T Govender

Publications and source records attributed to T Govender.

At least 19 recordsLinked to original sources
PubMed2006

Statistical optimisation of the mucoadhesivity and characterisation of multipolymeric propranolol matrices for buccal therapy.

A Box-Behnken experimental design was employed to optimise a polymeric blend for the preparation of propranolol HCl matrices with maximum mucoadhesivity and was thereafter modified for achieving controlled drug release. The quantitative effects of the polymers used i.e. poly(acrylic acid) (PAA) and poly(vinyl pyrrolidone) (PVP) on mucoadhesion could be predicted using polynomial equations. A formulation of 20% PAA, 20% CMC and 20% PVP was identified for maximising mucoadhesivity and obtaining a controlled drug release profile. Reproducibility of the optimal formulation in terms of mucoadhesivity and controlled drug release was confirmed. The optimal formulation was characterised in terms of mucoadhesivity, release kinetics, swelling/erosion, hydration dynamics and surface pH. From the model fitting analyses, drug release was found to be diffusion, polymeric relaxation and erosion based with the former two being more dominant over erosion. This was in agreement with the erosion and swelling studies which showed swelling and erosion occurring in the tablet matrix. Textural profiling showed initial rapid hydration, which could be beneficial for enhanced mucoadhesivity. Surface pH of the multipolymeric matrices was similar to salivary pH and did not show extremes in changes over the test period. The optimal preparation of multipolymeric propranolol matrices identified in this study shows potential for buccal administration.

Acrylic Resins↗
PubMed2006

Enhancing drug incorporation into tetracycline-loaded chitosan microspheres for periodontal therapy.

PURPOSE: To identify optimal formulation parameters for enhancing the incorporation of tetracycline hydrochloride into chitosan microspheres for periodontal therapy. METHODS: Tetracycline-loaded chitosan microspheres were prepared by ionotropic gelation. Various formulation parameters (salt form of drug, aqueous phase pH, anion structure, inorganic salts and electrolytes, preparation method) were investigated for their influence on drug incorporation efficiency. Microspheres were assessed in terms of drug entrapment and content, microsphere recovery, particle size and morphology. RESULTS: Although drug incorporation efficiency was increased marginally, the use of a dihydrate form of the drug was not considered feasible due to the lowered microsphere recovery and higher costs. A decrease in the aqueous pH from 9 to 6 enhanced drug incorporation efficiency without an adverse effect on microsphere morphology. The use of inorganic salts/electrolytes and other approaches of microsphere preparation did not significantly enhance drug incorporation efficiency and these approaches also adversely affected microsphere morphology. The ionotropic preparation method in terms of the drug loading technique significantly affected drug incorporation efficiencies. CONCLUSIONS: This study has shown that formulation variables can be exploited in order to enhance the incorporation of a water soluble drug into chitosan microspheres using the ionotropic gelation technique. Based on a comparison of all results obtained with the different approaches, the modification of the aqueous phase to pH 6 was identified as the most feasible approach.

Anions↗
PubMed2005

Optimisation and characterisation of bioadhesive controlled release tetracycline microspheres.

A Box-Behnken experimental design was employed to statistically optimise the formulation parameters of a tetracycline microsphere preparation for maximum bioadhesivity and controlled drug release. The quantitative effect of the formulation parameters at different levels on bioadhesion and drug release could be predicted using polynomial equations. A formulation comprising of 3% (w/w) chitosan, 10% (w/w) tetracycline HCl and 9% (w/v) tripolyphosphate was identified for maximising bioadhesivity and obtaining controlled drug release. The optimal microsphere preparation was subsequently characterised in terms of hydration dynamics, release kinetics, antimicrobial activity, thermal properties, morphology and surface pH. Kinetic models revealed that drug release followed Fickian diffusion while textural analysis showed minimal hydration over the test period. Antimicrobial studies showed that the drug concentrations in the in vitro release samples were above the minimum concentration of drug required for inhibition of Staphylococcus aureus growth. Thermal analyses showed a possible interaction between the drug and polymer. Scanning electron microscopy confirmed the integrity of the microspheres and identified the morphological changes following drug release. Surface pH of the microspheres was similar to salivary pH and did not show extremes in changes over the test period.

Adhesiveness↗
PubMed2005

Synthesis of a novel PEG-block-poly(aspartic acid-stat-phenylalanine) copolymer shows potential for formation of a micellar drug carrier.

A novel functionalised copolymer with three polymeric components, poly(ethylene glycol)-block-poly(aspartic acid-stat-phenylalanine), PEG-P(asp-phe), was synthesised and investigated for its potential to form micelles via ionic interactions with a model water-soluble drug, diminazene aceturate. Drug-free solutions of structurally related PEG-P(asp-phe) 5:6:4 and PEG-P(asp-phe) 5:4:6 copolymers indicated polymeric aggregation into micellar-type constructs. The size of PEG-P(asp-phe) 5:6:4 micelles was found to be pH and drug content-dependent. The drug-loaded systems existed as discreet units and were fairly uniform in size and shape. More drug could be included in the PEG-P(asp-phe) 5:6:4 micelles as compared to if only interaction with carboxyl groups from aspartic acid units was responsible for micelle formation, indicating the augmentative role of phenylalanine moieties in drug-incorporation. The slower in vitro drug release from PEG-P(asp-phe) 5:6:4 micelles as compared to PEG-Pasp (AB) micelles indicated the role of the phenylalanine moiety in controlling drug release. This study, therefore, confirmed the potential of a novel tri-component copolymer structure, PEG-P(asp-phe), for the formation of polyionic micelles for drug delivery.

Chemical Phenomena↗
PubMed2005

Toll-like receptor 3 gene polymorphisms in South African Blacks with type 1 diabetes.

Type 1 diabetes is the consequence of exposure of genetically susceptible individuals to specific environmental precipitants. The innate immune system provides the initial response to exogenous antigen and links with the adaptive immune system. The aim of this study was to assess the role of polymorphisms occurring in the cytoplasmic region of toll-like receptor (TLR) 3 gene and immediate 5' sequence, in subjects of Zulu descent with type 1 diabetes in KwaZulu-Natal, South Africa. Seventy-nine subjects with type 1 diabetes and 74 healthy normal glucose tolerant gender-matched control subjects were studied. Parts of exon 4 and exon 3/intron 3 of the TLR3 gene were studied by polymerase chain reaction, direct sequencing and restriction enzyme digestion with Bts 1. Of the nine polymorphisms studied, a significant association with type 1 diabetes was found for the major allele in the 2593 C/T polymorphism and for the minor alleles in the 2642 C/A and 2690 A/G polymorphisms, which were found to be in complete linkage disequilibrium. Correction of the P-values for the number of alleles studied, however, rendered the results no longer significant. These results suggest that polymorphisms in the TLR3 gene, which is part of the innate immune system, may be associated with type 1 diabetes in this population.

Adult↗
PubMed2003

Low molecular weight quaternised chitosan (I): synthesis and characterisation.

For a better understanding of the behaviour of macromolecules in vitro and in vivo, their structural and chemical properties that may be influential as experimental variables need to be characterised. N-Trimethyl chitosan chloride and N-triethyl chitosan chloride have been synthesised from chitosan to increase the solubility range of these polymers. However, little is known about the effect of the degree of quaternisation, molecular weight, viscosity and different substitution groups on the polymer's ability to enhance the transport of large hydrophilic compounds, such as peptide and protein drugs, across intestinal and nasal epithelia and on their toxicity profile. This study describes the synthesis of various quaternised chitosan polymers from low and medium molecular weight chitosan. These polymers were characterised to determine if any relationships between their degree of quaternisation, molecular weight and viscosity could be found which will determine their behaviour as absorption enhancers in future studies.

Absorption↗
PubMed2002

Polymorphisms in various coagulation genes in black South African women with placental abruption.

This pilot study examined Factor V Leiden (R506Q), prothrombin (20210G-->A), thrombomodulin (A455V) and MTHFR (677C-->T) in 100 Zulu-speaking black South African women with placental abruption and 217 controls. The Factor V Leiden and prothrombin variant gene alleles were not detected in either patient or control groups. The thrombomodulin polymorphic variant was not seen in the patient group but three heterozygotes (1%) were found in the controls. No homozygotes for the MTHFR T677 variant were detected in the patients but two (1%) were noted in the controls; the normal and heterozygote genotype and allele frequencies for this polymorphism were similar in the two groups.

Abruptio Placentae↗
PubMed2001

Drug-polyionic block copolymer interactions for micelle formation: physicochemical characterisation.

While covalent attachment of small drug molecules to AB copolymers for the formation of polymeric micelles for drug delivery has been investigated, few studies have focused on non-covalent interactions. The aim of this study was therefore to explore the potential of non-covalent interactions between an AB copolymer, Poly(aspartic acid)-poly(ethylene glycol) (Pasp-PEG), with anionic pendant groups and diminazene aceturate, a small molecular weight cationic drug. Micelles were prepared by mixing solutions of Pasp-PEG and diminazene in 25 mM Tris-HCl buffer. At all Pasp-PEG concentrations studied, the micelles appeared to be water soluble with a unimodal size distribution and ranged in size from approximately 22 to 60 nm. The polyionic micelles also displayed similar and small absolute zeta potential values at various drug:monomer molar ratios which confirmed stabilisation by the PEG corona. The scattering intensity was maximal and remained unchanged, while particle size increased slightly at pH range from 3.4 to 7.2. At this pH range both the polymer and drug would be ionised and ionic interactions possible to drive micellar formation. An increase in size and scattering intensity with addition of NaCl to the micelles was attributed to dehydration of the PEG corona which may have led to aggregation of the micelles. The absence of micellar dissociation upon addition of salt was attributed to the dominance of hydrogen bonding between Pasp and diminazene aceturate, as assessed by isothermal titration microcalorimetry. Morphological evaluation of these constructs showed them to be discrete and fairly uniform in size and shape. This study was therefore successful in confirming the potential of non-covalent interactions using an AB copolymer to form polyionic micelles for drug delivery.

Drug Delivery Systems↗
PubMed2001

Soluble transferrin receptors in anaemia of pregnancy.

Anaemia is one of the most common disorders in pregnancy. The most common cause is iron deficiency. Iron deficiency anaemia is relatively easy to diagnose using a serum ferritin of <15 ng/ml. However, because ferritin is an acute phase reactant, the diagnosis of iron deficiency anaemia in hospitalised or ill patients may be difficult, since serum ferritin may be normal or raised, even in the face of iron deficiency. Soluble transferrin receptor assay (STfR) may be useful in these situations because it reflects the degree of iron requirement in relation to supply, and it is not an acute phase reactant. This study was undertaken to detect subclinical anaemia in pregnant women and to correlate STfR assay with the current diagnostic tests for iron deficiency anaemia. One hundred and fifty-three consenting pregnant women seen at the antenatal clinic at King Edward VIII Hospital (KEH) were recruited. Women on haemantinics, who had renal failure, haemoglinopathy and blood transfusion in the past 3 months, were excluded. An ELISA technique was used for the assay of STfR while standard methodology was used for the other biochemical and haematological assays (FBC, urea, creatinine, c reactive protein and iron studies). One hundred and fifty subjects were included in the final analysis. Seventy-two (48%) had varying degrees of iron deficiency anaemia. In 70% (105) of the samples analysed, serum ferritin and STfR agreed on the presence/absence of iron deficiency anaemia. STfR and S:F were 75% and 86% sensitive; 63% and 82% specific, respectively. The calculated positive and negative predictive values are: STfR 64% and 75%; S:F 84% and 87%; Hb 58% and 57%; mean corpuscular volume 91% and 55%, respectively. Ferritin remains the gold standard for the diagnosis of iron deficiency anaemia. However, because ferritin is an acute phase reactant, soluble transferrin receptor assay may be a better test in ill and hospitalised patients where ferritin may be normal or elevated, despite iron deficiency.

Journal Article↗
PubMed2000

Defining the drug incorporation properties of PLA-PEG nanoparticles.

The drug incorporation and physicochemical properties of PLA-PEG micellar like nanoparticles were examined in this study using a model water soluble drug, procaine hydrochloride. Procaine hydrochloride was incorporated into nanoparticles made from a series of PLA-PEG copolymers with a fixed PEG block (5 kDa) and a varying PLA segment (3-110 kDa). The diameter of the PLA-nanoparticles increased from 27.7 to 174.6 nm, with an increase in the PLA molecular weight. However, drug incorporation efficiency remained similar throughout the series. Incorporation of drug into the smaller PLA-PEG nanoparticles made from 3:5, 15:5 and 30:5 copolymers did not influence the particle size, while an increase was observed for the larger systems comprising 75:5 and 110:5 copolymers. An increase in drug content for PLA-PEG 30:5 nanoparticles was achieved by increasing the theoretical loading (quantity of initially present drug). The size of these nanoparticles remained unchanged with the increasing drug content, supporting the proposed micellar type structure of the PLA-PEG 30:5 nanoparticles. The morphology of these systems remained unchanged both at low and high theoretical drug loadings. Formulation variables, such as an increase in the aqueous phase pH, replacement with the base form of the drug and inclusion of lauric acid in the formulation did not improve the incorporation efficiency of drug into PLA-PEG 30:5 nanoparticles. While poly(aspartic acid) as a complexation agent did not improve the drug incorporation efficiency of procaine hydrochloride, it did so for another water soluble drug diminazene aceturate. This may be attributed to a stronger interaction of diminazene aceturate with poly(aspartic acid) relative to procaine hydrochloride, as confirmed by thermodynamic analysis of isothermal titration calorimetric data. The drug incorporation and physicochemical characterisation data obtained in this study may be relevant in optimising the drug incorporation and delivery properties of these potential drug targeting carriers.

Anesthetics, Local↗
PubMed2000

Hydrogen bonding and electrostatic interaction contributions to the interaction of a cationic drug with polyaspartic acid.

PURPOSE: To determine the mechanism and identify forces of interaction between polyaspartic acid and diminazene (a model drug). Such knowledge is essential for the design of polymeric drug delivery systems that are based on molecular self-assembly into complexes or micellar type systems. METHODS: Complex formation was studied by isothermal titration microcalorimetry and the McGhee von Hippel model was applied to obtain K(obs), deltaH(obs), and n(obs). The calorimetry data were compared with both an optical density study and the amount of free/complexed drug. RESULTS: The diminazene-polyaspartic acid interaction is enthalpically driven, whereby one diminazene molecule interacts with two monomers of polyaspartic acid. The dependence of K(obs) on salt concentration reveals a contribution of electrostatic interactions. However, applying Manning's counter ion condensation theory shows that the major driving force for the complex formation is hydrogen bonding, with interfacial water molecules remaining buried within the complex. The modelling of the pH dependence of K(obs) and deltaH(obs) demonstrates that the ionization of carboxylic groups of polyaspartic acid is a prerequisite for the interaction. CONCLUSIONS: Complex formation between diminazene and polyaspartic acid is driven by both electrostatic interactions and hydrogen bonding, with the latter being the dominating force. Although electrostatic interactions are not the major driving force, ionization of the drug and polymer is essential for complex formation.

Cations↗
PubMed1999

PLGA nanoparticles prepared by nanoprecipitation: drug loading and release studies of a water soluble drug.

The nanoprecipitation technique for preparation of nanoparticles suffers the drawback of poor incorporation of water soluble drugs. The aim of this study was therefore to assess various formulation parameters to enhance the incorporation of a water soluble drug (procaine hydrochloride) into poly(dl-lactide-co-glycolide) (PLGA) nanoparticles prepared by this technique. Approaches investigated for drug incorporation efficiency enhancement included the influence of aqueous phase pH, replacement of procaine hydrochloride with procaine dihydrate and the inclusion of excipients: poly(dl-lactide) (PLA) oligomers, poly(methyl methacrylate-co-methacrylic acid) (PMMA-MA) or fatty acids into the formulation. The nanoparticles produced were submicron size (<210 nm) and of low polydispersity. It was found that an aqueous phase pH of 9.3, replacement of procaine hydrochloride with procaine dihydrate and the incorporation of PMMA-MA, lauric and caprylic acid into the formulation could enhance drug incorporation efficiency without the size, morphology and nanoparticle recovery being adversely influenced. For instance changing the aqueous phase pH from 5.8 to 9.3 increased nanoparticle recovery from 65.1 to 93.4%, drug content from 0.3 to 1.3% w/w and drug entrapment from 11.0 to 58.2%. However, the presence of high ratios of lauric acid and procaine dihydrate in the formulation adversely affected the morphology and size of the nanoparticles. Also, PLA oligomers were not considered a feasible approach since it decreased drug entrapment from 11.0 to 8.4% and nanoparticle recovery from 65.1 to 19.6%. Drug release from nanoparticles appears to consist of two components with an initial rapid release followed by a slower exponential stage. This study has demonstrated that formulation variables can be exploited in order to enhance the incorporation of a water soluble drug into PLGA nanoparticles by the nanoprecipitation technique.

Buffers↗
PubMed1999

Complex formation between the anionic polymer (PAA) and a cationic drug (procaine HCI): characterization by microcalorimetric studies.

PURPOSE: Due to the importance of drug-polymer interactions in, inter alia, drug loading/release, supramolecular assemblies and DNA delivery for gene therapy, the aim of this study was therefore to establish the mechanism of interaction between a model polymer (Polyacrylic acid, PAA) and a model drug (procaine HCl). METHODS: This was performed by studying the effect of salt (KCl) concentration on their heat released values using Isothermal Titration Microcalorimetry (ITM). The integrated released heat data were computer fitted to a one class binding model and the thermodynamic parameters (Kobs, deltaH, and N) were determined. RESULTS: As the KCl concentration was increased, Kobs decreased thus establishing the salt dependence of the interaction. The linear variation of deltaGobs with deltaSobs indicated that their interaction was entropically driven. The stoichiometry of the interaction was calculated to be one procaine molecule per monomer of PAA. Dissection of the total observed free energy at each KCI concentration indicated that the contribution of the non-electrostatic attractions to the interaction of PAA with procaine HCl was greater than those of the electrostatic attractions. CONCLUSIONS: We have shown that the interaction between PAA and procaine HCl is dependent upon the presence of counterions (monovalent ions) and is mainly entropically driven. The calculated stoichiometry indicated that one procaine HCl molecule neutralised one carboxylic acid group on PAA. Although electrostatic interactions were necessary for initiating complex formation, the non-electrostatic forces were dominant in stabilising the PAA-procaine HCl complex.

Acrylic Resins↗
PubMed1990

125I-insulin binding to circulating erythrocytes, monocytes and cultured fibroblasts in non-obese patients with polycystic ovarian disease.

The insulin receptor status of circulating erythrocytes, monocytes and cultured fibroblasts were studied in non-obese Indian women with polycystic ovarian disease (PCOD) with no clinical evidence of acanthosis nigricans and age, height and weight matched reference subjects. The women with polycystic ovaries had decreased mean maximum specific binding to erythrocytes (PCOD 7.4 +/- 0.6%, normal women 11.5 +/- 0.3%; p less than 0.0001) and monocytes (PCOD 2.4 +/- 0.3%, normal women 4.1 +/- 0.4%; p less than 0.003) when compared to the normal women. This decreased binding was attributed to a change in both receptor number and affinity. 125I-insulin binding to cultured fibroblasts revealed similar mean maximum specific binding and affinity values in both groups studied. Although further work is necessary to exclude genetic or post-receptor defects, it is likely that an environmental factor is implicated in the decreased 125I-insulin binding to erythrocytes and monocytes.

Adult↗
PubMed1988

The SimulTRAC FT4/TSH assay evaluated as a first-line thyroid-function test.

We evaluated the SimulTRAC FT4 57Co/TSH 125I dual-isotope assay for the simultaneous measurement of free thyroxin (FT4) by radioimmunoassay analog techniques and of thyrotropin (TSH) by immunoradiometry. Inter- and intra-assay CVs were less than 10% over the entire range tested except for 15.9% at the lowest FT4 concentration. Results obtained by the SimulTRAC assay allowed complete differentiation of 85 hyperthyroid patients and 35 hypothyroid patients from normal subjects. However, such estimations of FT4 or TSH concentrations occasionally were misleading for assessing thyroid status in various clinical conditions. We conclude that the SimulTRAC assay has the same inherent disadvantages possessed by FT4 analog and TSH immunoradiometric assays; however, where results of one of the simultaneous assays may be misleading, the results provided by the other may indicate the underlying pathology without requiring an additional assay.

Adult↗
PubMed1987

Insulin binding to circulating monocytes and erythrocytes in patients with non-insulin-dependent diabetes in the young.

125I-insulin binding to circulating monocytes and erythrocytes was carried out in 9 patients with non-insulin-dependent diabetes in the young (NIDDY), who belonged to families in which non-insulin-dependent diabetes was transmitted through 3 generations. The diabetics had a decreased mean maximum specific binding to monocytes 2.1 (1.1-4.1%) compared to 4.0 (2.6-6.2%) in their age, sex and weight matched reference subjects. This decreased binding was primarily due to a decrease in receptor number as all diabetics had normal affinity values (2-10 ng/ml). We have attributed the decreased binding in NIDDY to the down regulatory effect of the basal hyperinsulinemia (23.6 +/- 3.2 vs 11.7 +/- 0.5 microU/ml). By contrast the maximum specific binding to erythrocyte was similar in both groups (9.7 +/- 0.5; 8.9 +/- 0.5%; p greater than 0.5).

Adolescent↗