Modelling and optimization of microneedles for transdermal drug delivery

Microneedle mediated drug delivery is an amalgam of the conventional transdermal patch and the hypodermic needle injection. It offers an improved drug delivery technique without the limitations of the above methods. The ability of microneedles to increase permeability of substances in the skin has been established in the literature. However, a quantitative method for predicting the performance of microneedle devices prior to their fabrication is yet to be fully developed. The contribution of this research is a theoretical framework for modelling and optimizing microneedle array design to obtain desired drug delivery rate while taking into account the transport and mechanical properties of the skin. This is achieved by exploring various theories surrounding transdermal drug transport. The existing theories are then used to develop models to link the microneedle array design parameters with drug transport properties such as permeability and drug concentration in blood. Numerical simulations and theoretical analyses that are carried out in this PhD research indicate that microneedle design has a significant effect on drug delivery. An algorithm was developed for solving the series of equations presented, thus obtaining a framework which is applied to predict performance of microneedle arrays in vivo. Some practical scenarios are also simulated to demonstrate the applicability of the developed framework. For example, numerical simulations of transdermal delivery of Fentanyl show that varying the design parameters such as penetrated length of microneedle and the tip radius of microneedles affected the peak blood concentration. Similarly, the developed framework was used to obtain the optimum microneedle design to calculate the desired peak blood concentration similar to that obtained using conventional patch system. This study is relevant as it provides a better understanding of microneedle mediated drug delivery process and it orchestrates the design and hence, fabrication of more efficient microneedle based drug delivery devices

Modelling transdermal drug delivery using microneedles: effect of geometry on drug transport behaviour

Transdermal drug delivery using microneedles (MNs) depends on the rate of drug transport through the viable epidermis. Therefore, minimising the distance between the drug-loaded surface and the microcirculation in the dermis where the drug is absorbed into the body is significant in improving drug delivery efficiency. A quantifiable relationship between MN design parameters and skin diffusion properties is therefore desirable, which is what this study aims to achieve. A framework is presented to quantitatively determine the effects of design parameters on drug diffusion through skin, where the effects of compressive strain on skin due to insertion of MN are considered. The model is then used to analyse scenarios of practical importance. For all scenarios analysed, predicted steady-state flux was found to be lower when effect of MN strain on diffusion coefficient was accounted for. For example, simulations results indicated increasing tip radius from 5 to 20 μm and flux increased from 6.56 × 10 to 7.02 × 10 mol/(m s) for constant diffusion coefficient. However, if the effect of strain on diffusion coefficient is considered, the calculated flux increases from 5.30 × 10 to a peak value of 5.32 × 10 mol/(m s) (at 10 μm) and decreases to 5.29 × 10 mol/(m s). This paper contributes by reporting a framework to relate MN geometry to permeability with inclusion of the possible effects the MN design may pose on the diffusion coefficient. © 2011 Wiley Periodicals, Inc. and the American Pharmacists Association

Simulation based optimization of microneedle geometry to improve drug permeability in skin

Microneedles are a method of transdermal drug delivery which overcomes the barrier of the stratum corneum by piercing through with little or no pain. Microneedle have been shown to increase the skin permeability but the extent to which they do so is affected by the design of the microneedles due to certain parameters such as tip radius, base radius, pitch, number of microneedles on the patch and penetration depth. In this study a framework is developed to optimize these parameters and an optimum geometry for a microneedle shape is proposed. Simulations using two different softwares where then carried out to analyze the effect of these parameters on the diffusive flux and concentration of the drug in the blood. We found that the results of the numerical optimization and the results from the computer simulations led to the same conclusion about the optimum dimensions for the chosen geometry

Evaluation of nuclear medicine awareness in Nigeria; perspective of Lagos state radiographers

Diagnostic Nuclear Medicine makes use of radioisotopes with the aid of ionizing radiation for the early diagnosis of disease conditions. This study aims to assess the awareness and knowledge of diagnostic nuclear medicine amongst radiographers in Lagos state and its importance in the field of diagnosis. Methods: The study is a descriptive, cross-sectional study using questionnaires administered by the researcher without coercion. The questionnaires were administered to 175 participants. Ethical considerations were of paramount importance by eligibility to be part of the category includes being a radiographer that works in Lagos State, under an RRBN certified institution. The questionnaire was divided into socio-demographic section, awareness of nuclear medicine and the knowledge about the specialty. Data collected was tabulated, categorized and analysed with statistical software - IBMSPSS Statistics 21. Results: A total of 175 radiographers participated in this study. The age range of the respondents was between 20 – 60 years with a mean age of 34.7 years. 112 (64%) are between the ages of 20 and 35 years, 51 (29.1%) are between 36 and 50, while 12 (6.9%) are 51 years and above. 166 (94.9%) of radiographers admitted to having previous knowledge about nuclear medicine, while 9 (5.1%) said they had no prior knowledge of the medical specialty. 2(1.1%) were the only respondents who had participated in carrying out nuclear medicine procedures. 109 (62.3%) between the ages of 20 and 35 years which represents the youngest age group has the highest rate of awareness about nuclear medicine.162 (92.6%) of the respondents agreed the urgent need for the establishment of more standardized centres in Nigeria. Conclusion: Diagnostic nuclear medicine is a very important diagnostic specialty and highly essential in the medical sector of every country. Despite the level of awareness amongst radiographers, only 1.1% has participated in nuclear medicine procedures and this could be attributed to lack of equipments in Nigeria which also reflects the level of development as a whole

Risk management and performance of deposit money banks in Nigeria: A re-examination

Risks inherent in banking businesses should be managed to prevent financial losses to the sector’s stakeholders and negative externalities to the global economy. To this end, this study examines the effect of risk management on the performance of deposit money banks in Nigeria. A sample of eight (8) deposit money banks with international authorization are purposively selected out of 12 deposit money banks due to data availability. Panel data analysis techniques were adopted to analyze the secondary data that were obtained from the annual reports of banks. Findings based on the disaggregated model results reveal that both liquidity and capital risk variables exert a negative but insignificant effect on performance. However, credit risk drives performance of the internationally authorized banks positively and significantly. Furthermore, Management quality (MQ) is the only control variable that has a significant influence on the performance of the selected deposit money banks. The study concludes that credit risk and management quality significantly and positively drive performance among the financial entities

Transdermal drug delivery by microneedles: does skin metabolism matter?

Microneedle arrays have been shown to increase skin permeability for the transdermal delivery of drugs with high molecular weights. Various theoretical studies have been proposed to predict the drug transport behaviour after drug injection using microneedles. However it is important for the optimal design of microneedle systems to consider the effects of biological factors such as skin metabolism and variations in pharmacokinetic parameters as well as to improve the enhancement of skin permeability. A mathematical model for microneedle systems is introduced and applied to simulate the verapamil transport with metabolism in the skin. A comparative analysis for a transdermal delivery of verapamil from microneedles is presented in this paper. The results indicate that the skin metabolism does not markedly affect the skin permeation after verapamil injection using microneedles

Influence of array interspacing on the force required for successful microneedle skin penetration: theoretical and practical approaches

Insertion behaviour of microneedle (MN) arrays depends upon the mechanical properties of the skin and, MN geometry and distribution in an array. In addressing this issue, this paper studies MN array insertion mechanism into skin and provides a simple quantitative basis to relate the insertion force with distance between two MNs. The presented framework is based on drawing an analogy between a beam on an elastic foundation and mechanism of needle insertion, where insertion force is separated into different components. A theoretical analysis indicates that insertion force decreases as interspacing increases. For a specified skin type, insertion force decreased from 0.029 to 0.028N/MN when interspacing at MN tip was increased from 50μm (350μm at MN base) to 150μm (450μm at MN base). However, dependence of insertion force seems to decrease as the interspacing is increased beyond 150μm. To assess the validity of the proposed model, a series of experiments was carried out to determine the force required for skin insertion of MN. Experiments performed at insertion speed of 0.5 and 1.0mm/s yielded insertion force values of 0.030 and 0.0216N, respectively, for 30μm interspacing at MN base (330μm interspacing at tip) and 0.028 and 0.0214N, respectively, for 600μm interspacing at MN base (900μm interspacing at tip). Results from theoretical analysis and finite element modelling agree well with experimental results, which show MN interspacing only begins to affect insertion force at low interspacing (<150μm interspacing at MN base). This model provides a framework for optimising MN devices, and should aid development of suitable application method and determination of force for reliable insertion into skin. © 2013 Wiley Periodicals, Inc

Population genomics diversity of Plasmodium falciparum in malaria patients attending Okelele Health Centre, Okelele, Ilorin, Kwara State, Nigeria.

Background: Plasmodium falciparum, the most dangerous malaria parasite species to humans remains an important public health concern in Okelele, a rural community in Ilorin, Kwara State, Nigeria. There is however little information about the genetic diversity of Plasmodium falciparum in Nigeria. Objective: To determine the population genomic diversity of Plasmodium falciparum in malaria patients attending Okelele Community Healthcare Centre, Okelele, Ilorin, Kwara State. Methods: In this study, 50 Plasmodium falciparum strains Merozoite Surface Protein 1, Merozoite Surface Protein 2 and Glutamate Rich Protein were analysed from Okelele Health Centre, Okelele, Ilorin, Nigeria. Genetic diversity of P. falciparum isolates were analysed from nested polymerase chain reactions (PCR) of the MSP-1 (K1, MAD 20 and RO33), MSP-2 (FC27 and 3D7) and Glutamate Rich Protein allelic families respectively. Results: Polyclonal infections were more in majority of the patients for MSP-1 allelic families while monoclonal infections were more for MSP-2 allelic families. Multiplicity of infection for MSP-1, MSP-2 and GLURP were 1.7, 1.8 and 2.05 respectively Conclusion: There is high genetic diversity in MSP \u2013 2 and GLURP allelic families of Plasmodium falciparum isolates from Okelele Health Centre, Ilorin, Nigeria

Microneedles from fish scale biopolymer

This article reports on microneedles produced from biopolymer films extracted from fish scales of tilapia (Oreochromiss sp.) using micromolding technique. Evaluation of the properties of polypeptide films prepared from the fish scales gave refractive index (1.34), protein concentration (78%), ash content (1.6%) at (22%) moisture content. The microneedles successfully inserted into artificial skin models and imaging using digital camera showed microneedles remained intact when inserted and when removed from the skin model. Microneedles also successfully inserted into porcine skin and were shown to dissolve gradually at 0 s, 60 s, 120 s, and 180 s after insertion. Microneedles containing methylene blue as model drug were also produced and successfully pierced porcine skin. 3D finite element (FEM) simulations were performed using the measured mechanical properties of the biopolymer films (Young's modulus 0.23 N/mm2 and tensile strength 1.8105 N/mm2) to evaluate the stress distribution on various dimensions of the fish scale derived microneedles and hence, their ability to withstand force necessary to pierce the skin without fracture. Results from mechanical analysis using FEM showed that microneedles with tip radius between 10 and 100 μm could withstand up to 0.12 N of force per microneedle without fracture, which is indicated when the stress at the tip of the microneedle exceeds the ultimate stress of the material of fabrication. Using skin insertion tests and finite element simulations, this study provides evidence that microneedles fabricated from fish scale biopolymer can effectively pierce and degrade into skin and therefore are good candidate for transdermal applications

Farmers’ willingness to cultivate pro-vitamin A cassava variety in Kwara State, Nigeria

The study examined factors underlying farmers’ perception about pro-vitamin-A cassava varieties and their willingness to cultivate them in Kwara State, Nigeria. One hundred and twenty-two (122) cassava farmers, selected through a multistage sampling procedure, were used for the study.  Data were collected through use of interview schedule and analysed using percentages, mean and standard deviation. Chi-square, likelihood ratio and factor (principal component) analysis were used for inferential deduction. Results showed about half (50.8%) of the respondents had high knowledge about the improved cassava variety and a vast majority (93.4%) expressed willingness to cultivate it. Sex (χ2 = 3.542) and knowledge level (χ2 = 15.732) had significant association with willingness to cultivate at p<0.05, with female farmers found to be about 3 times more likely willing to cultivate than male. Also, farmers with more knowledge were found to be about 6 times more likely willing to cultivate pro-vitamin-A than those with little knowledge. Three crucial factors (‘ethno-based preference’, ‘culturally induced personal preference’ and ‘colour dislike’) were found to be associated with farmers’ perception about the cassava variety. Farmers in Kwara State were willing to cultivate the pro-vitamin-A cassava variety. Women and those who had more knowledge were more willing to cultivate the variety than men and those with little knowledge, respectively. Factors underlying farmers’ perception about the variety were linked to ethnic/cultural background and dispreference for yellow root cassava. The need for more female integration and increased nutritional education in the drive towards popularisation of pro-vitamin-A cassava variety are recommended