Nanovectors for Neurotherapeutic Delivery Part II: Polymeric Nanoparticles

Despite major advances in intracranial surgery and delivery of drugs to the brain, treatment of neurological diseases remains one of the great medical challenges of our days. The complexity of the organ makes surgical procedures complicated, and conventional systemic delivery of drugs to the brain is hampered by low drug selectivity and low drug partitioning over the blood-brain barrier. Due to the high social and economic impacts related to diseases of the central nervous system, development of new improved treatments of brain related disorders is of significant value, both for the patient and for the society. Nanomedicine is a rapidly growing field in the development of novel therapies for treatments of brain pathologies. The scientific progress in nanotechnology has resulted in several new innovative nano-assemblies, with promising medical potentials. Therapeutic benefits related to the use of nanovectors includes, reduced chemical and enzymatic degradation of drugs, increased uptake over biological barriers, improved selectivity by surface modification using targeting ligands, and reduced toxic side effects in non-target tissue. This review discusses various applications of polymeric nanoparticles as nanovectors in treatment of neuronal diseases, specifically illustrated for Alzheimer’s and Parkinson’s diseases and Glioblastoma

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

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 o

In Vitro and In Vivo evaluation of a hydrogel-based microneedle device for transdermal electro-modulated analgesia

With a significant portion of the world suffering from chronic pain, the management and treatment of this condition still requires extensive research to successfully mobilize and functionalize its sufferers. This article details the in vitro and in vivo evaluation of a transdermal electro-modulated hydrogel-microneedle array (EMHM) device for the treatment of chronic pain. In vitro characterization of the electro-modulated hydrogel was undertaken before the determination of the in vivo release, histopathologic and pharmacokinetic profiles of the EMHM in a Sprague Dawley rat model. Pharmacokinetic modeling was conducted to establish a level A in vitro-in vivo correlation. Data analysis was carried out by segmenting the combined in vivo release profile into individualistic profiles before analysis

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 (±0.4540 mg) as compared to electro-stimulation (±2.93 mg)