4. Electronic Theses and Dissertations (ETDs) - Faculties submissions
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Item Design and synthesis of a nanocapsule system for transdermal delivery of lignocaine across the skin(University of the Witwatersrand, Johannesburg, 2024) Makha, Lerato Mathabelo; Choonara, Yahya E.; Ubanako, Philemon; Makhathini, SifisoPain is a major health problem that is caused by an emotional and sensory experience due to injury of tissues and can be differentiated as acute or chronic. Pain protects humans by assisting in making us aware that there is body injury or potentially damaging situations. If acute pain is not treated correctly, it can lead to chronic pain. Pain can be treated by several classes of medications including analgesics, Non-steroidal Anti-inflammatory drugs (NSAIDs), opioids, anti-depressants, and local anaesthetics. These medicines are administered orally. Although this is the preferred route of administration, it has many inherent limitations that can negatively impact the drug's desired pharmacological effects. Since the skin is the most convenient and accessible region for medication administration, innovative delivery techniques like Transdermal Drug Delivery Systems (TDDS) have been developed to circumvent the drawbacks of traditional drug delivery routes. This method has displayed fewer side effects experienced with conventional oral medications like gastric irritation and first-pass hepatic metabolism causing low blood concentration of the drug leading to low therapeutic effect. Nonetheless, the stratum corneum (SC), the skin's outermost layer, functions as a strong barrier to prevent most medications from penetrating the skin. Much attention has been paid to the use of nanocarriers as a transdermal delivery system of different accessible pharmaceuticals through the SC with the potential to have local or systemic effects to treat various disorders (Alexander et al., 2012). The purpose of this report was to synthesize Lignocaine (LIG)-loaded nanocapsules to evaluate their potential to transport LIG across the skin for increased effectiveness and fewer side effects. Lignocaine-loaded nanocapsules (LIG-PLGA-PC) were prepared by employing the solvent displacement technique. Aqueous phase consisted of 200 mg of Tween® 80 in 30 ml of purified water. The mixture was ultrasonicated for few minutes then put under electronic magnetic agitation. Organic phase was prepared by dissolving 125 mg of PLGA, 250 mg of PC and 30 mg of LIG in 5 ml of chloroform. Under probe sonication, organic phase was added drop wise to the aqueous phase and was allowed to stir overnight to remove the organic solvent. The formulated nanosystem was then frozen and lyophilized (FreeZone® 2,5, Labconco®, Kansas City, MS, USA) at -80 °C for 48 hours to yield a powder and analyzed using different analytical techniques. Four samples were prepared with three samples having a drug loaded in the organic phase. The fourth sample was blank, without the drug in the organic phase. The synthesised nanoparticles were characterized using Scanning Electron Microscopy (SEM), zetasizer, Ultraviolet (UV) spectroscopy, Fourier transform infrared (FTIR) spectroscopy and Thermogravimetric Analysis (TGA). SEM clarified the configuration of the surface and shape of the nanocapsules by beaming electrons that interacted with the sample's atoms to produce three-dimensional surface topography. Using the zeta-sizer, the size of nanoparticles was found to be around 139.8 nm and a polydispersity index (PDI) of 0.182 a while the zeta potential was -48,2 mV. A drug entrapment efficacy (DEE) percentage of 72 % was achieved. LIG release studies showed a sustained release over a 24-hour period. The FTIR spectral evaluation of drug loaded sample showed a vibration at 3000–2800 cm−1 indicating a N-H stretch, and 1750-1735 cm−1 presented with a C=O stretching group. At 1250–1020 cm−1 there is a C-N stretching confirming the presence of an amine group. Thermogravimetric Analysis (TGA) thermal studies indicated that the LIG nanoparticulate structure increased the thermal stability of LIG. To investigate the biocompatibility of the nanoformulation, immortalized human keratinocytes (HaCaT) were treated with LIG-PLGA-PC copolymeric nanocapsules and an MTT (3-(4,5- dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide) assay was conducted to evaluate the cytotoxicity of the treatments. Absorbance values were measured at 570 nm employing a Thermo Lab systems Multiskan MK3 microplate reader. From the cytotoxicity study conducted, at 48-hour, LIG-PLGA-PC nano formulation showed increased cell viability of 102, 103, and 110 % for 6,25 μg/ml, 3,125 μg/ml, 1,5625 μg/ml concentrations respectively. The blank nanocapsule showed a cell viability of 99, 98 and 100 % at concentrations of 6,25 μg/ml, 3,125 μg/ml, and 1,5625 μg/ml. The HaCaT cell micrographs showed cell proliferation on the drug loaded as well as plain drug figures. This can be confirmed by the MTT assay that the nanoformulation was non-cytotoxic with predicted biocompatibility. The combined experiments and findings of the LIG-PLGA-PC nanocapsule synthesis demonstrated that further studies and investigations are required to show that these nanoparticles can be used as a possible formulation for TDDS medication delivery of LIG for pain treatment.Item Patients’ perspectives, pain, and health-related quality of life in same-day discharge hip and knee arthroplasty(University of the Witwatersrand, Johannesburg, 2024) Van Heerden, Martin Harry; Keller, Monique M; Lord, SandyBackground International protocols for same-day discharge (SDD) following total hip (THA) and total knee arthroplasty (TKA) have recently been introduced in South Africa. Comparisons between recovery trajectories of THA and TKA patients in traditional length-of-stay models and SDD are limited. The impact of SDD related to pain, health-related quality of life and the patient perspective has yet to be studied in the South African context. Aim This study aimed to explore, evaluate, and compare patients' perspectives, experiences, pain, and health-related quality of life (HRQOL) following SDD after THA and TKA. Method A mixed-methods design was implemented with a collection of patient-reported outcome measures (PROMs) over six weeks (n=109: 55 THA and 54 TKA) and concluded with semi-structured interviews (n=24: 14 THA and 10 TKA). Participants scheduled for SDD THA and TKA who met the study criteria were selected through convenience sampling. Descriptive and inferential statistics were used, and a thematic analysis of interview data was conducted. Results There were significant improvements in PROMs by six weeks postoperatively in both groups. Significant between-group differences revealed persistent neuropathic pain (P=0.536) and worse health-related quality of life scores (p=0.102) in the TKA group. The themes identified highlight positive perspectives of SDD, emphasising unique challenges in the SDD TKA group. Findings indicate that patients undergoing SDD THA and TKA in South Africa produce results comparable to those in international studies. Conclusion This research advocates for a holistic approach in SDD THA and TKA, emphasising patient-centric care, effective communication, and preparation. The study contributes insights into this evolving clinical pathway and encourages further researchItem Impact of a rural context in Kwazulu Natal on primary caregiver's management of pain innon-communicating children with severe neurological impairment(University of the Witwatersrand, Johannesburg, 2024) Pretorius, Jeanette; Franzsen, DeniseUntreated pain is known to have negative consequences on the development and wellbeing of “non-verbal” children with severe neurological impairment (SNI). Healthcare workers and caregivers must ensure that pain is managed in this population, even though pain may be difficult to assess. Occupational therapists need to understand how context affects the management of pain experienced by a child with SNI, as well as its impact on the care of the child. This study determined how a rural KwaZulu Natal context impacted how primary caregivers recognized and manage pain and the care of their child with SNI. Methods: A multiple descriptive, embedded case study design using a demographic and pain questionnaire, with cross sectional design. There were nine respondents’ qualitative and quantitative information content analysis and descriptive statistics were used to report. Results: Financial, environmental, emotional and physical strain factors associated with the rural context were identified may be adding to the burden of care and affecting the occupational performance of the child with SNI and their caregiver. Specific difficulties included limits in access to clean running water, the practice of bed sharing and poor infrastructure affecting access to healthcare facilities. Primary care givers also mentioned their other responsibilities in the house and the physical strain of caring for a child with SNI affected them and their child. Despite this, all primary care givers were able to recognise and act when their child was in pain and relied on crying duration and intensity as a reliable sign of pain in their child. All primary care givers were confident in their ability and method of recognising and addressing pain in their child with SNI. More experienced primary caregivers used fewer signs to recognise when their child with SNI was in pain. Conclusions: A rural African context is associated with barriers and opportunities for the care, the recognition- and management of pain in children with SNI. More research related to supporting participation and occupational performance by addressing the effects of pain in children with SNI on the child and the primary caregiver living in rural contexts is required