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Nanotherapeutics: Enabling Vitamin D3 as a Multifaceted Nutraceutical
Published in Bhupinder Singh, Minna Hakkarainen, Kamalinder K. Singh, NanoNutraceuticals, 2019
Krantisagar S. More, Vinod S. Ipar, Amit S. Lokhande, Anisha A. D’souza, Padma V. Devarajan
Liposomes for topical application of vitamin D3 and its derivatives, particularly calcitriol, were less greasy than the usual paraffin ointments, and at the same time, provided good skin penetration ability (Naeff et al., 1998). Merz (1994) investigated incorporation of four different vitamin D-derivatives (lα, 25-Dihydroxycholecalciferol, 25-Hydroxycholecalciferol, Pro- 25(OH)2,-D3, Calcipotriol) in liposomal membranes to optimize their use for psoriasis treatment. However, it is also reported that under certain conditions, vitamin D3 derivatives show a hypercalcemic activity that can be a serious limitation in their use for a dermatological application like psoriasis (Soleymani et al., 2015). Nevertheless, one report suggests that liposomal vitamin D3 preparations can achieve a given antipsoriatic effect with reduced concentration of the active substance, thereby reducing the risk of skin irritation and of hypercalcemia (Dattagupta et al., 1998). The antiparakeratotic potency of liposomal vitamin D3 in a concentration of 2 μg/g was twice compared to commercial preparation containing a higher concentration of 4 μg/g in a mouse tail test (Korbel et al., 2001). Vitamin D3-3-bromoacetate derivative (AMPI-109) was encapsulated into phospholipid nanosomes using the SuperFluids™ critical fluid nanosome (CFN) process. The nanosomes reduced tumor size up to 39% (Castor, 2016).
Barriers in the Tumor Microenvironment to Nanoparticle Activity
Published in Dan Peer, Handbook of Harnessing Biomaterials in Nanomedicine, 2021
Hanan Abumanhal-Masarweh, Lilach Koren, Omer Adir, Maya Kaduri, Maria Poley, Gal Chen, Aviram Avital, Noga Sharf Pauker, Yelena Mumblat, Jeny Shklover, Janna Shainsky-Roitman, Avi Schroeder
Since CAFs are a key factor responsible for nanoparticles’ limited diffusion and distribution in the TME [102, 108], they represent an attractive target for adjuvant treatment that can be applied to achieve higher efficacy in translation. One approach focuses on CAFs genetic depletion leading to extensive remodeling of the tumor ECM with a total decrease in its stiffness, hence, enhancing the ability of nanoparticles to diffuse and reach deeper tumor regions [109, 110]. However, genetic intervention pronounced by CAFs reduction might induce cancer cell proliferation and result in an increased aggressiveness of the tumor [111]. Alternative approaches rely on indirect targeting of CAFs by manipulating relative regulatory pathways or inhibition of fibroblast activation protein (FAP) in order to obtain solid stress alleviation. In pancreatic cancer, it was demonstrated that vitamin D receptor (VDR) regulates pancreatic stellate cells’ (PSCs-myofibroblast-like cells) activation state. Upon administration of calcipotriol, a vitamin D analog, reprogramming of CAFs was achieved to reach a non-activated state, therefore enabling improved chemotherapeutic response [112]. Similarly, pharmacological inhibition of FAP’s enzymatic activity resulted in inhibition of tumor growth in several indirect routes such as decrease in blood vessel density, decrease in myofibroblast content and inhibition of tumor cell proliferation [113]. Targeting CAFs as an adjuvant therapy facilitates improved nanoparticle distribution and penetration into deeper layers in solid tumors, increasing cellular uptake and thus improving anti-tumor efficacy [26, 114].
Optimization of clobetasol propionate loaded niosomal gel for the treatment of psoriasis: Ex vivo and efficacy study
Published in Journal of Dispersion Science and Technology, 2022
Psoriasis is chronic inflammatory skin disease characterized by relapsing episodes of lesions, impaired epidermal differentiation, hyperplasia, leukocyte infiltration, localization of rash, plaques, erythroderma, pustular and hyperkeratosis. It affects around 2–3% of worldwide population, hindering the quality of life and aggravates psychosocial tension.[1] In psoriasis, topical treatment with corticosteroids is the first choice as it overcomes the side-effects associated with systemic therapy.[2] However, due to thick psoriatic stratum corneum and low permeability of corticosteroids (like clobetasol propionate), the effective management with topical therapy is very challenging.[3] In recent years, researchers have gained much attention to improve the topical treatment of corticosteroids including the work by Kumar et al.,[4] where the cyclosporine loaded liposomes were developed and the clinical trials showed promising data in chronic plaque psoriasis. Romero et al. prepared amorphous cyclosporine A loaded nanoparticles which showed 6-fold increase in the dermal permeation compared to cyclosporine powder.[5] Tripathi et al. developed methotrexate laden nanostructured lipid carrier (NLC) gel to improve drug permeation for effective treatment of psoriasis.[6] Pradhan et al. demonstrated the potential of solid lipid nanoparticles (SLN) to improve permeation of fluocinolone acetonide for topical treatment of psoriasis.[7] Tekko et al. sustained intradermal delivery of methotrexate by applying nano-crystal microneedle approach.[8] Algahtani et al. used nanoemulsion approach to deliver curcumin for effective psoriasis treatment.[9] Qadir et al. optimized NLC to deliver herbal drugs and noted improved permeation to treat psoriasis in rat model.[10] Rapalli et al. optimized solid lipid nanoparticles of apremilast and observed improved cell uptake in HaCat cell linings.[11] Pradhan et al. developed calcipotriol loaded nanostructured lipid carriers (NLCs) and demonstrated 3.6-fold increase in drug deposition in skin for effective treatment of psoriasis.[12] They also integrated fluocinolone acetonide in NLCs with salicylic acid and observed high efficacy in animal studies.[13] Shalaby et al. developed betamethasone-salicylic acid loaded cubosomal gel to improve skin permeation and anti-psoriatic activity.[14] Simioni et al. improved anti-psoriatic activity of Vitamin D3 using nanostructured archaeolipid carriers.[15]