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Fulltext Performance of transdermal therapeutic systems: Effects of biological factors

Singh I, Morris AP

Int J Pharm Investig, 2011 Jan;1(1):4-9.
PMID: 23071913 DOI: 10.4103/2230-973X.76721

Transdermal drug delivery (TDD) is a technique that is used to deliver a drug into the systemic circulation across the skin. This mechanism of drug delivery route has many advantages, including steady drug plasma concentrations, improved patient compliance, elimination of hepatic first pass, and degradation in the gastrointestinal tract. Over the last 30 years, many transdermal products have been launched in the market. Despite the inherent advantages of TDD and the growing list of transdermal products, one of the major drawbacks to TDD is the occurrence of inter- and intraindividual variation in the absorption of the drug across the skin. A majority of these variations are caused by biological factors, such as gender, age, ethnicity, and skin hydration and metabolism. These factors affect the integrity and the barrier qualities of the skin, which subsequently result in the variation in the amount of drug absorbed. The main objective of this review article is to provide a concise commentary on the biological factors that contribute to the variation in transdermal permeation of drugs across human skin and the available transdermal therapeutic systems that may reduce the variations caused by biological factors.
An evaluation of tocotrienol ethosomes for transdermal delivery using Strat-M® membrane and excised human skin

Nair RS, Billa N, Leong CO, Morris AP

Pharm Dev Technol, 2021 Feb;26(2):243-251.
PMID: 33274672 DOI: 10.1080/10837450.2020.1860087

Tocotrienol (TRF) ethosomes were developed and evaluated in vitro for potential transdermal delivery against melanoma. The optimised TRF ethosomal size ranged between 64.9 ± 2.2 nm to 79.6 ± 3.9 nm and zeta potential (ZP) between -53.3 mV to -62.0 ± 2.6 mV. Characterisation of the ethosomes by ATR-FTIR indicated the successful formation of TRF-ethosomes. Scanning electron microscopy (SEM) images demonstrated the spherical shape of ethosomes, and the entrapment efficiencies of all the formulations were above 66%. In vitro permeation studies using full-thickness human skin showed that the permeation of gamma-T3 from the TRF ethosomal formulations was significantly higher (p
Characterization and ex vivo evaluation of curcumin nanoethosomes for melanoma treatment

Nair RS, Billa N, Mooi LY, Morris AP

Pharm Dev Technol, 2022 Jan 06.
PMID: 34957920 DOI: 10.1080/10837450.2021.2023568

This study aimed at developing curcumin nanoethosomes (Cur-Ets) with superior skin permeation intended for melanoma treatment. Although curcumin is active against many types of skin cancers, a suitable topical formulation is still lacking due to its hydrophobicity and poor skin permeation. The formulation was characterized using Scanning Transmission Electron Microscopy (STEM), atomic force microscopy (AFM), ATR-FTIR, DSC and XRD. In vitro skin permeation was carried out using human skin, and the cytotoxicity of the formulation was evaluated on human melanoma cells (SK-MEL28). The vesicle size and zeta potential of the Cur-Ets were determined as 67 ± 1.6 nm and -87.3 ± 3.3 mV, respectively. STEM and AFM analysis further support the size and morphology of the formulation. Curcumin's compatibility with formulation additives was confirmed by ATR-FTIR analysis. In addition, DSC and XRD analyses showed successful drug encapsulation in nanoethosomes. The drug encapsulation efficiency was determined as 87 ± 0.9%. The skin permeation of curcumin from Cur-Ets showed a superior flux (0.14 ± 0.03 µg cm-2 h-1) compared to the control (p
Physicomechanical properties of sintered scaffolds formed from porous and protein-loaded poly(DL-lactic-co-glycolic acid) microspheres for potential use in bone tissue engineering

Boukari Y, Scurr DJ, Qutachi O, Morris AP, Doughty SW, Rahman CV, et al.

J Biomater Sci Polym Ed, 2015;26(12):796-811.
PMID: 26065672 DOI: 10.1080/09205063.2015.1058696

An injectable poly(DL-lactic-co-glycolic acid) (PLGA) system comprising both porous and protein-loaded microspheres capable of forming porous scaffolds at body temperature was developed for tissue regeneration purposes. Porous and non-porous (lysozyme loaded) PLGA microspheres were formulated to represent 'low molecular weight' 22-34 kDa, 'intermediate molecular weight' (IMW) 53 kDa and 'high molecular weight' 84-109 kDa PLGA microspheres. The respective average size of the microspheres was directly related to the polymer molecular weight. An initial burst release of lysozyme was observed from both microspheres and scaffolds on day 1. In the case of the lysozyme-loaded microspheres, this burst release was inversely related to the polymer molecular weight. Similarly, scaffolds loaded with 1 mg lysozyme/g of scaffold exhibited an inverse release relationship with polymer molecular weight. The burst release was highest amongst IMW scaffolds loaded with 2 and 3 mg/g. Sustained lysozyme release was observed after day 1 over 50 days (microspheres) and 30 days (scaffolds). The compressive strengths of the scaffolds were found to be inversely proportional to PLGA molecular weight at each lysozyme loading. Surface analysis indicated that some of the loaded lysozyme was distributed on the surfaces of the microspheres and thus responsible for the burst release observed. Overall the data demonstrates the potential of the scaffolds for use in tissue regeneration.
A dual-application poly (dl-lactic-co-glycolic) acid (PLGA)-chitosan composite scaffold for potential use in bone tissue engineering

Boukari Y, Qutachi O, Scurr DJ, Morris AP, Doughty SW, Billa N

J Biomater Sci Polym Ed, 2017 Nov;28(16):1966-1983.
PMID: 28777694 DOI: 10.1080/09205063.2017.1364100

The development of patient-friendly alternatives to bone-graft procedures is the driving force for new frontiers in bone tissue engineering. Poly (dl-lactic-co-glycolic acid) (PLGA) and chitosan are well-studied and easy-to-process polymers from which scaffolds can be fabricated. In this study, a novel dual-application scaffold system was formulated from porous PLGA and protein-loaded PLGA/chitosan microspheres. Physicochemical and in vitro protein release attributes were established. The therapeutic relevance, cytocompatibility with primary human mesenchymal stem cells (hMSCs) and osteogenic properties were tested. There was a significant reduction in burst release from the composite PLGA/chitosan microspheres compared with PLGA alone. Scaffolds sintered from porous microspheres at 37 °C were significantly stronger than the PLGA control, with compressive strengths of 0.846 ± 0.272 MPa and 0.406 ± 0.265 MPa, respectively (p
Fulltext Genome-wide association study in a Chinese population identifies a susceptibility locus for type 2 diabetes at 7q32 near PAX4

Ma RC, Hu C, Tam CH, Zhang R, Kwan P, Leung TF, et al.

Diabetologia, 2013 Jun;56(6):1291-305.
PMID: 23532257 DOI: 10.1007/s00125-013-2874-4

AIMS/HYPOTHESIS: Most genetic variants identified for type 2 diabetes have been discovered in European populations. We performed genome-wide association studies (GWAS) in a Chinese population with the aim of identifying novel variants for type 2 diabetes in Asians.
METHODS: We performed a meta-analysis of three GWAS comprising 684 patients with type 2 diabetes and 955 controls of Southern Han Chinese descent. We followed up the top signals in two independent Southern Han Chinese cohorts (totalling 10,383 cases and 6,974 controls), and performed in silico replication in multiple populations.
RESULTS: We identified CDKN2A/B and four novel type 2 diabetes association signals with p
Genome-wide association analysis provides insights into the molecular etiology of dilated cardiomyopathy

Zheng SL, Henry A, Cannie D, Lee M, Miller D, McGurk KA, et al.

Nat Genet, 2024 Nov 21.
PMID: 39572783 DOI: 10.1038/s41588-024-01952-y

Dilated cardiomyopathy (DCM) is a leading cause of heart failure and cardiac transplantation. We report a genome-wide association study and multi-trait analysis of DCM (14,256 cases) and three left ventricular traits (36,203 UK Biobank participants). We identified 80 genomic risk loci and prioritized 62 putative effector genes, including several with rare variant DCM associations (MAP3K7, NEDD4L and SSPN). Using single-nucleus transcriptomics, we identify cellular states, biological pathways, and intracellular communications that drive pathogenesis. We demonstrate that polygenic scores predict DCM in the general population and modify penetrance in carriers of rare DCM variants. Our findings may inform the design of genetic testing strategies that incorporate polygenic background. They also provide insights into the molecular etiology of DCM that may facilitate the development of targeted therapeutics.