Sunaina Indermun

Current advances in the fabrication of microneedles for transdermal delivery

The transdermal route is an excellent site for drug delivery due to the avoidance of gastric degradation and hepatic metabolism, in addition to easy accessibility. Although offering numerous attractive advantages, many available transdermal systems are not able to deliver drugs and other compounds as desired. The use of hypodermic needles, associated with phobia, pain and accidental needle-sticks has been used to overcome the delivery limitation of macromolecular compounds. The means to overcome the disadvantages of hypodermic needles has led to the development of microneedles for transdermal delivery. However, since the initial stages of microneedle fabrication, recent research has been conducted integrating various fabrication techniques for generating sophisticated microneedle devices for transdermal delivery including progress on their commercialization. A concerted effort has been made within this review to highlight the current advances of microneedles, and to provide an update of pharmaceutical research in the field of microneedle-assisted transdermal drug delivery systems.

A review of the chemical modification techniques of starch

Starch is a naturally occurring storage copolymer with unique physicochemical properties. There are, however, some key structural properties of starch that can be modified in order to functionalize the copolymer to meet specific requirements. Specifically, the chemical modification of starch provides a variety of physicochemical benefits, some of which have been used previously to functionalize preformed drug delivery systems. Of the three main chemical modification methods reviewed (namely: oxidation, esterification and etherification), surface chemical oxidation introduces more pertinent physicochemical properties that increase overall drug delivery system efficacy and applicability. Surface oxidation evidently is the more preferable chemical modification method of pre-formed starch particles and has the greatest potential for further development when compared to the other reviewed chemical modification methods. The use of modified starch in clinical trials as well as the potential future implications of these systems is also included in this review.

An interfacially plasticized electro-responsive hydrogel for transdermal electro-activated and modulated (TEAM) drug delivery

This paper highlights the use of hydrogels in controlled drug delivery, and their application in stimuli responsive, especially electro-responsive, drug release. electro-conductive hydrogels (ECHs) displaying electro-responsive drug release were synthesized from semi-interpenetrating networks (semi-IPNs) containing a poly(ethyleneimine) (PEI) and 1-vinylimidazole (VI) polymer blend as the novel electro-active species. The semi-IPNs are systems comprised of polyacrylic acid (PAA) and poly(vinyl alcohol) (PVA). This paper attempts to investigate the various attributes of the electro-responsive ECHs, through institution of a statistical experimental design. The construction of a Box-Behnken design model was employed for the systematic optimization of the ECH composition. The design model comprised of three variables, viz. poly(ethyleneimine) volume; 1-vinylimidazole volume; and applied voltage, critical to the success of the formulation. Electro-responsive drug release was determined on formulations exposed to varying environments to ascertain the optimal environment for the said desired release. A comparison method of formulation water content and swelling through gravimetric analysis was also conducted. Matrix resilience profiles were obtained as an insight to the ability of the ECH to revert to its original structure following applied stress. Response surface and contour plots were constructed for various response variables, namely electro-responsive drug release, matrix resilience and degree of swelling. The outcomes of the study demonstrated the success of electro-responsive drug release. The findings of the study can be utilized for the development of electro-responsive delivery systems of other drugs for the safer and effective drug delivery. Volumes of poly(ethyleneimine) (>2.6 mL) and 1-vinylimidazole (>0.7 mL), resulted in ideal therapeutic electro-responsive drug release (0.8 mg) for indomethacin. Lower amounts of poly(ethyleneimine) and amounts of 1-vinylimidazole ranging from 0.2 to 0.74 mL are consistent with greater than 1.6 mg release per stimulation. Swelling of <25-45% was seen.

Patient-Controlled Analgesia: Therapeutic Interventions Using Transdermal Electro-Activated and Electro-Modulated Drug Delivery

Chronic pain poses a major concern to modern medicine and is frequently undertreated, causing suffering and disability. Patient-controlled analgesia, although successful, does have limitations. Transdermal delivery is the pivot to which analgesic research in drug delivery has centralized, especially with the confines of needle phobias and associated pain related to traditional injections, and the existing limitations associated with oral drug delivery. Highlighted within is the possibility of further developing transdermal drug delivery for chronic pain treatment using iontophoresis-based microneedle array patches. A concerted effort was made to review critically all available therapies designed for the treatment of chronic pain. The drug delivery systems developed for this purpose and nondrug routes are elaborated on, in a systematic manner. Recent developments and future goals in transdermal delivery as a means to overcome the individual limitations of the aforementioned delivery routes are represented as well. The approval of patch-like devices that contain both the microelectronic-processing mechanism and the active medicament in a small portable device is still awaited by the pharmaceutical industry. This anticipated platform may provide transdermal electro-activated and electro-modulated drug delivery systems a feasible attempt in chronic pain treatment. Iontophoresis has been proven an effective mode used to administer ionized drugs in physiotherapeutic, diagnostic, and dermatological applications and may be an encouraging probability for the development of devices and aids in the treatment of chronic pain.

Drug Delivery Strategies for Antivirals against Hepatitis B Virus

Chronic hepatitis B virus (HBV) infection poses a significant health challenge due to associated morbidity and mortality from cirrhosis and hepatocellular cancer that eventually results in the breakdown of liver functionality. Nanotechnology has the potential to play a pivotal role in reducing viral load levels and drug-resistant HBV through drug targeting, thus reducing the rate of evolution of the disease. Apart from tissue targeting, intracellular delivery of a wide range of drugs is necessary to exert a therapeutic action in the affected organelles. This review encompasses the strategies and techniques that have been utilized to target the HBV-infected nuclei in liver hepatocytes, with a significant look at the new insights and most recent advances in drug carriers and their role in anti-HBV therapy.

Stimuli-responsive polymers as smart drug delivery systems: Classifications based on carrier type and triggered-release mechanism

Abstract Stimuli-responsive or smart polymeric drug delivery is a dynamic research field, involving the use of natural or synthetic polymers that are engineered to exert therapeutic effects in response to physicochemical and physiological processes as well as externally applied stimuli. Often termed as “smart” polymers, “environmental-sensitive” polymers, or “intelligent” polymers, these polymers are unique in that they have the ability to rapidly modify their microstructure to minor environmental changes and revert to their original state once the stimulus is removed. This chapter overviews the use of stimuli-responsive polymers and their successful application in the broad field of drug delivery. The various types of stimulus responses as well as the categories of the subsequently developed responsive materials will be detailed. Examples of the stimuli responses discussed include physiological changes in temperature, pH, and blood plasma constituents as well as externally applied stimuli such as electric current, photo-stimulation, and magnetic fields. Furthermore, these polymers are classified based on their carrier type and subsequent delivery mechanism. Emphasis on recent, more advanced stimuli-responsive systems is further provided with the future potential of these drug delivery techniques highlighted.

3D Printed, PVA–PAA Hydrogel Loaded-Polycaprolactone Scaffold for the Delivery of Hydrophilic In-Situ Formed Sodium Indomethacin

3D printed polycaprolactone (PCL)-blended scaffolds have been designed, prepared, and evaluated in vitro in this study prior to the incorporation of a polyvinyl alcohol–polyacrylic acid (PVA–PAA) hydrogel for the delivery of in situ-formed sodium indomethacin. The prepared PCL–PVA–PAA scaffold is proposed as a potential structural support system for load-bearing tissue damage where inflammation is prevalent. Uniaxial strain testing of the PCL-blended scaffolds were undertaken to determine the scaffold’s resistance to strain in addition to its thermal, structural, and porosimetric properties. The viscoelastic properties of the incorporated PVA–PAA hydrogel has also been determined, as well as the drug release profile of the PCL–PVA–PAA scaffold. Results of these analyses noted the structural strength, thermal stability, and porosimetric properties of the scaffold, as well as the ability of the PCL–PVA–PAA scaffold to deliver sodium indomethacin in simulated physiological conditions of pH and temperature. The results of this study therefore highlight the successful design, fabrication, and in vitro evaluation of a 3D printed polymeric strain-resistant supportive platform for the delivery of sodium indomethacin.

Ex vivo evaluation of a microneedle array device for transdermal application.

A new approach of transdermal drug delivery is the use of microneedles. This promising technique offers the potential to be broadly used for drug administration as it enables the dramatic increase in permeation of medicaments across the stratum corneum. The potential of microneedles has evolved to spawn a plethora of potential transdermal applications. In order to advance the microneedle capabilities and possibly revolutionize advanced drug delivery, this study introduces a novel transdermal electro-modulated hydrogel-microneedle array (EMH-MNA) device composed of a nano-porous, embeddable ceramic microneedle array as well as an optimized EMH for the electro-responsive delivery of indomethacin through the skin. The ex vivo permeation as well as drug release experiments were performed on porcine skin tissue to ascertain the electro-responsive capabilities of the device. In addition, the microbial permeation ability of the microneedles across the viable epidermis in both microneedle-punctured skin as well as hypodermic needle-punctured skin was determined. Ex vivo evaluation of the EMH-MNA device across porcine skin demonstrated that without electro-stimulation, significantly less drug release was obtained (±0.4540mg) as compared to electro-stimulation (±2.93mg).