Surface modified kokum butter lipid nanoparticles for the brain targeted delivery of nevirapine

Solid Lipid Nanoparticles for Drug Delivery: Pharmacological and Biopharmaceutical Aspects

“…As we will discuss later, drugs whose site of action is at the CNS level always represent a challenge in terms of biodistribution in order to achieve effective concentrations in the brain. Lipid NPs of zidovudine and saquinavir intended for the CNS showed promising results in cell cultures in vitro (Kuo and Wang, 2014;Joshy et al, 2016), and SLN-based formulations of efavirez (Gupta et al, 2017) and nevirapine (Lahkar and Kumar Das, 2018) exhibited an improved central in vivo bioavailability (BA). In the case of efavirenz, the strategy was to circumvent the BBB by means of the nasal administration of the nanoparticles, while in the nevirapine case the administration was by intravenous (IV) route and the improved biodistribution was attributed to the coating (polysorbate 80), able to enrich the protein crown in ApoE, resulting in a higher passage through the BBB due to the contribution of receptor-mediated transcytosis (Li et al, 2018;Krishna et al, 2019).…”

Nanoprecipitation: Applications for Entrapping Active Molecules of Interest in Pharmaceutics

“…As intended, pegylation of polymeric nanoparticles extends the elimination half-life by $100 h and increases in 84% the AUC regarding the free drug [27]. With respect to lipid carriers, Lahkar et al [13] evidence a significant increase of their AUC 0-t which could remain in the blood circulation four times more than the free drug. Moreover, modifications to the particle surface providing some hydrophilicity with polysorbate 80 result in an MRT eight times higher than that of the free drug.…”

“…To this end, rotary evaporation [14, 18, 22-24, 31, 55] and centrifugation [5, 6, 12, 13, 15, 16, 23, 25, 27-29, 36, 56, 57] are the most used methods; however, filtration [4,6,16,18,24] and dialysis [7-9, 21, 27, 34] have also been reported. Likewise, lyophilization is the preferred technique to stabilize the nanoparticles, although the storage to low temperatures has been used to preserve the aqueous dispersions [5,8,9,13,21,29].…”

“…Stability of the particle dispersions has been investigated by using refrigerated storage [6,8,13,15,21], room temperature at 25°C [8,13,14,21,57], and accelerated conditions varying between 35 and 40°C [8,9,11,20,27]. Particle size, PDI, and zeta potential are usually followed during the storage time, and the physical integrity of the dispersions is observed for up to 6 months.…”

“…Some of the research works undertaken during the last years have proposed the vectorization in nanoparticles, via nanoprecipitation, of hydrophobic active molecules, mainly exhibiting logP values higher than 3. They include antineoplastics (e.g., doxorubicin [4], paclitaxel [5,6], docetaxel [7,8], methotrexate [9], triptolide [6], cucurbitacin [10], and sorafenib [11]), antiretrovirals (e.g., efavirenz [12] and nevirapine [13]), immune suppressants (mycophenolate [14]), anti-inflammatories (clobetasol [15], fluticasone propionate [16], dexamethasone [17,18], and diclofenac [19]), antimicrobial and antifungal agents (polymyxin B [20], amphotericin B [21], itraconazole [22], and linezolid [23]), antihyperlipidemics (fenofibrate [24,25]), anesthetics (tetracaine [26] and ketamine [27]), antihypertensives (nimodipine [28] and atenolol [29]), vitamins or their precursors (β-carotene [30] and vitamin E [31]), and antioxidants (quercetin [14,32]). Likewise, although in a much smaller number, hydrophilic active molecules such alendronate [33], N-acetylcysteine [34], and calcein [35], have been investigated.…”