ABSTRACT
Microneedle (MN) delivery devices are more accepted by people than regular traditional needle injections (e.g. vaccination) due to their simplicity and adaptability. Thus, patients of chronic diseases like diabetes look for alternative pain-free treatment regimens circumventing regular subcutaneous injections. Insulin microneedles (INS-MNs) are a thoughtfully researched topic (1) to overcome needle phobia in patients, (2) for controlled delivery of the peptide, (3) decreasing the frequency of drug administration, (4) to ease the drug administration procedure, and (5) thus increasing patient adherence to the treatment dosage regimes. MNs physically disrupt the hard outer skin layer to create minuscule pores for insulin (INS) to pass through the dermal capillaries into the systemic circulation. Biodegradable polymeric MNs are of greater significance for INS and vaccine delivery than silicon, metal, glass, or non-biodegradable polymeric MNs due to their ease of fabrication, mass production, cost-effectiveness, and bioerodability. In recent years, INS-MNs have been researched to deliver INS through the transdermal implants, buccal mucosa, stomach wall, intestinal mucosal layers, and colonic mucosa apart from the usual transdermal delivery. This review focuses on the design characteristics and the applications of biodegradable/dissolvable polymeric INS-MNs in transdermal, intra-oral, gastrointestinal (GI), and implantable delivery. The prospective approaches to formulate safe, controlled-release INS-MNs were highlighted. Biodegradable/dissolvable polymers, their significance, their impact on MN morphology, and INS release characteristics were outlined. The developments in biodegradable polymeric INS-MN technology were briefly discussed. Bio-erodible polymer selection, MN fabrication and evaluation factors, and other design aspects were elaborated.
Subject(s)
Drug Delivery Systems , Insulin , Humans , Administration, Cutaneous , Drug Delivery Systems/methods , Polymers , Injections, Subcutaneous , Needles , SkinABSTRACT
Cerebral small vessel disease (CSVD) represents a spectrum of pathological processes of various etiologies affecting the brain microcirculation that can trigger neuroinflammation and the subsequent neurodegenerative cascade. Prevalent with aging, CSVD is a recognized risk factor for stroke, vascular dementia, Alzheimer disease, and Parkinson disease. Despite being the most common neurodegenerative condition with cerebrocardiovascular axis, understanding about it remains poor. Interestingly, modifiable risk factors such as unhealthy diet including high intake of processed food, high-fat foods, and animal by-products are known to influence the non-neural peripheral events, such as in the gastrointestinal tract and cardiovascular stress through cellular inflammation and oxidation. One key outcome from such events, among others, includes the cellular activations that lead to elevated levels of endogenous cellular-derived circulating microparticles (MPs). MPs can be produced from various cellular origins including leukocytes, platelets, endothelial cells, microbiota, and microglia. MPs could act as microthrombogenic procoagulant that served as a plausible culprit for the vulnerable end-artery microcirculation in the brain as the end-organ leading to CSVD manifestations. However, little attention has been paid on the potential role of MPs in the onset and progression of CSVD spectrum. Corroboratively, the formation of MPs is known to be influenced by diet-induced cellular stress. Thus, this review aims to appraise the body of evidence on the dietary-related impacts on circulating MPs from non-neural peripheral origins that could serve as a plausible microthrombosis in CSVD manifestation as a precursor of neurodegeneration. Here, we elaborate on the pathomechanical features of MPs in health and disease states; relevance of dietary patterns on MP release; preclinical studies pertaining to diet-based MPs contribution to disease; MP level as putative surrogates for early disease biomarkers; and lastly, the potential of MPs manipulation with diet-based approach as a novel preventive measure for CSVD in an aging society worldwide.
ABSTRACT
Progress in nanoscience and nanotechnology laid foundation for nanotherapy-based approach in cancer drug delivery for improved therapy and quality of life. The prepared polymeric nanoparticles (PNPs), PCL, PLGA and PLA NPs help in delivering paclitaxel (TAX) in vivo by avoiding the use of unsafe excipient, Cremophore EL. The classy microscopic examination SEM, TEM and AFM analysis revealed the spherical and smooth structure of the NPs as well as their homogeneous solid matrix without any amorphous arrangements. The FTIR analysis of PNPs exposed that there was no chemical interaction between polymer, stabilizer and TAX. The (1)H NMR and XRD analyses illustrate molecular dispersion of TAX in the polymeric matrix and no evidence was observed for the presence of crystalline TAX. The outcome of in vivo acute toxicity study endorses residual solvent free PNPs. The PNPs demonstrate excellent control in delivering TAX up to 48 h with best fitted to First-order, Baker-Lonsdale, Higuchi and Korsmeyer-Peppas model. The log plasma concentration-time profile shows that the prepared PNPs were safe and have much less side-effects. The pharmacokinetic study results illustrate increase in mean residence time as result of long circulating nature of the prepared nanoparticles, which helps them to reach target area. The estimated pharmacokinetic parameters AUC0-∞ (ng h)/mL, AUMC0-∞ (ng h(2))/mL, C max (ng/mL), t 1/2 (h), MRT (h), Cl (L/h/kg), V ss (L/kg) and V z (L/kg) shows improved therapeutic efficacy when compared with TAX solution.
