Propranolol‐Loaded Mesoporous Silica Nanoparticles for Treatment of Infantile Hemangiomas

Abstract

birth-weight, and premature infants. [3] The cause of IH onset has not been well elucidated, but IH has proven to be a disorder of angiogenesis and vasculogenesis with excessive proliferation of microvessels. [4] IH is often characterized by unique growth pattern with rapid proliferating phrase followed by spontaneous involution. [5] Due to the benign nature and tendency to resolve spontaneously, a "wait and see" strategy persisted in the past. However, some untreated IH will leave permanent changes, such as telangiectasias, scarring, skin atrophy, and fibro-fatty residual. Furthermore, about 10% of IH are destructive and problematic with the increasing risk for disfigurement and functional impairment. [6] Therefore, more active management in IH therapy instead of observation are often suggested by pediatricians. Currently, there are mainly three kinds of treatment methods for IHs, including drug therapy, laser therapy, and surgery. The individual treatment plan should be made according to the location, extent, depth, and biological phrase of the lesion and techniques available. [7] Given the discovery of its remarkable efficacy in treating proliferating IH since 2008, beta-adrenergic receptor blocker propranolol (PRN) has been widely used as the first-line therapy for IH. A great number of clinical studies (including retrospective study, prospective study, and meta-analysis) demon strated the efficacy of PRN in treating IH. [8] However, the bioavailability of PRN therapy in IH is always unsatisfactory. Our group previously investigated the pharmacokinetics of propranolol, and discovered that the peak plasma concentration of PRN was 383 ng mL −1 after administration of 1 mg kg −1 propranolol, and the elimination half-life was about 6 h. [9] Furthermore, PRN therapy for IH has been controversial due to the side effects. Although the short-term side effects are usually selflimiting and easy to manage, [10] such as bradycardia, bronchospasm, hypotension, hypoglycemia, electrolyte disturbances, and diarrhea, concerns regarding long-term neurocognitive effects have been raised recently due to the potentiality to penetrate the blood-brain-barrier and affect the central nervous system. [11] Consequently, there is an urgency to develop new approaches that could elevate the bioavailability of propranolol, extend the circulation time and lower the systemic toxicity of the drug.With the rapid development in nanotechnology, it is expected that novel treatments based on nanomedicine would be applied in the clinical practice in the near future. In the way of Infantile hemangioma (IH) is one of the most common neoplasm of infancy.Although with the potential to involute slowly after proliferation, IH has several subsets that could develop severe complications and lead to functional impairment or permanent disfigurement. In the present study, a novel propranolol (PRN) delivery system is developed that encapsulated in mesoporous silica nanoparticles (MSN). The primary nanoparticles are further treated with polyvinyl alcohol (PVA) ...

Infantile hemangioma

“…The original nanoparticles are then processed with polyvinyl alcohol (PVA) to form PVA-MSN-PRN nanoparticles. This novel nanodrug delivery system has been observed to have high therapeutic efficacy, low cytotoxicity, and such drugs may be administered more seldom, which makes it a promising strategy IH treatment [53].…”

Circular RNA hsa_circ_0000915 promotes propranolol resistance of hemangioma stem cells in infantile haemangiomas

“…1.5 × 10 6 HemSCs suspended in Matrigel (BD Matrigel ™ Basement Membrane) was implanted subcutaneously into the flanks of female nude mice (n = 5, day 0). Mice were treated with propranolol (10 mg/kg) by intraperitoneal injection every five days [33]. The hemangioma volume was measured and calculated using the formula: (width 2 × length)/2 at the indicated day.…”

Infantile Hemangiomas: An Update on Pathogenesis and Treatment

“…The novel methods of administration of propranolol include propranolol-loaded mesoporous silica nanoparticles and continuous delivery from liposomes-in-microspheres. Despite promising results in studies of tumor inhibition in mice, the safety of this type of therapy is yet to be established [26,27].…”