ABSTRACT
Despite being recognized as the "gold standard" for treating azole-resistant vulvovaginal candidiasis, amphotericin B (AmB), an amphoteric molecule, has not been widely used due to serious issues with solubility and permeability. In light of the aforementioned, the objective of the present study was to increase AmB's therapeutic efficacy by formulating it into an o/w nanoemulsion (AmB-NE) system. Furthermore, to facilitate AmB-NE's retention within the vaginal cavity, it was loaded into a mixture of Carbopol® 974P and Aloe vera-based gel (CA gel). Briefly, in the present study, a kinetically stable batch of formulated AmB-NE having a globule size of 76.52 ± 3.11 nm, PDI of 0.342 ± 0.032, and zeta potential of -22.32 ± 0.88 mV was incorporated into the CA gel base. This AmB-NE loaded gel (AmB-NE gel) exhibited a non-Fickian/anomalous diffusion from the hydrophilic matrix. The texture analysis of AmB-NE gel revealed that the prepared gel was a non-drip, soft, easy to spread, and sufficiently cohesive gel that could reside in the vaginal cavity, which was confirmed by our ex-vivo retention test, which revealed that AmB-NE loaded gel could stay in the vaginal cavity for approximately 11 h. Ex-vivo skin permeation studies revealed that AmB-NE is 4.26 times more permeable than AmB-coarse gel, implying that AmB-NE facilitates AmB entry into the vaginal epithelial layers. Furthermore, in-vivo vaginal lavage studies revealed that AmB-NE gel permeated 7.03-fold more than AmB-coarse gel. Prepared AmB-NE gel was stable in refrigerated condition and showed no histopathological toxicity. Thus, the present study suggests that AmB-NE gel could eliminate the existing problem of AmB and that it could serve as an alternative option to treat vulvovaginal candidiasis.
ABSTRACT
In an attempt to increase oral bioavailability and to target intestinal lymphatic transport system, Nimodipine loaded solid lipid nanoparticles (NMD-SLNs) were prepared. Nimodipine (NMD) is highly lipophilic antihypertensive drug having (logP 3.41) and 13% oral bioavailability. NMD-SLNs were prepared with palmitic acid (PA), poloxamer 188 and soya lecithin as a lipid, surfactant and co-surfactant respectively using high pressure homogeniser. A (2(3)) factorial design was employed; three factors such as lipid, surfactant and co-surfactant concentration were used. Parameters investigated includes particle size, polydispersity index (PDI), zeta potential, drug entrapment efficiency (EE %), drug loading efficiency (LE %), in vitro drug release of the SLNs. Optimised SLNs (F8) had particle size of 116±21 nm, zeta potential of -10±(-4.8) mV, EE of 93.66±9.72% and cumulative drug release of 87.52±2.54% in 10 h. The pharmacokinetic study of optimised SLNs conducted in male Albino Wistar rats showed 2.08-fold increase in relative bioavailability than that of NMD solution, when administered orally. Differential scanning calorimetry study revealed absence of any chemical interaction between NMD and PA while SEM study confirmed the non spherical shape of optimised SLNs. Accelerated stability studies showed that there was no significant change in the mean particle size and PDI after storage at 25±2°C/60±5% RH for the period of three months. Due to enhanced bioavailability, these NMD-SLNs are considered to be promising vehicles for oral delivery.
