Formulation and characterization of thiolated chitosan/polyvinyl acetate based microneedle patch for transdermal delivery of dydrogesterone.

Microneedle patches are promising transdermal drug delivery platforms with minimal invasiveness in a painless manner. Microneedle patch could be a promising alternate route for delivery of drugs having poor solubility and low bioavailability. This research work therefore, aimed to develop and characterize microneedle patch of thiolated chitosan (TCS) and polyvinyl acetate (PVA) for the systemic delivery of dydrogesterone (DYD). TCS-PVA-based microneedle patch was fabricated with 225 needles having a length of 575 µm with the sharp pointed end. Different ratios of TCS-PVA-based patch were employed to investigate the effects of mechanical tensile strength and percentage elongation. The scanning electron microscopy (SEM) revealed intact sharp-pointed needles. In vitro dissolution studies of microneedle patch (MN-P) were carried out by modified Franz-diffusion cell revealing the sustained release of DYD 81.45 ± 2.768 % at 48 hrs as compared to pure drug that showed 96.7 ± 1.75 % at 12 hrs. The transport of DYD (81%) across skin reaching the systemic circulation was evaluated through ex vivo permeation studies of MN-P. The skin penetration study through the parafilm M method showed good penetration with no deformation and breakage of needles along with no visible signs of skin irritation. Histological study of mice skins clearly showed the deeper penetration of needles into the skin. In summary, as-prepared MN-P show potential in developing an effective transdermal delivery system for DYD.

Oral delivery and enhanced efficacy of antimonal drug through macrophage-guided multifunctional nanocargoes against visceral Leishmaniasis.

The present study aimed on the site specific delivery and enhanced in-vivo efficacy of antimonial drugs against the visceral leishmaniasis via macrophage targeted mannose anchored thiomer based nanoparticles. Mannose anchored thiolated nanoformulation [M-(CS-g-PEI)-TGA] was developed and evaluated in terms particle size, zeta-potential and entrapment efficacy. The TEM and EDX analysis was carried out to evaluate the morphology and successful entrapment of antimonial drug. Mucodhesion, permeation enhancement, oral pharmacokinetics, and in-vivo anti-leishmanial activity were carried out. The M-(CS-g-PEI)-TGA were found to be spherical having particle size of 287 ± 20 nm. Ex-vivo permeation indicated a 7.39-fold enhanced permeation of Meglumine Antimoniate with M-(CS-g-PEI)-TGA across Caco-2 cells compared to the Glucantime. Evaluation of in-vitro reduction in the parasitic burden via flow cytometric analysis indicated a 5.7-fold lower IC50 for M-(CS-g-PEI)-TGA compared to Glucantime. A 6.1-fold improvement in the oral bioavailability and 5.2-fold reduced parasitic burden in the L. donovani infected BALB/c mice model was observed with M-(CS-g-PEI)-TGA compared to Glucantime. The results encouraged the concept of M-(CS-g-PEI)-TGA nanoformulations as a promising strategy for oral therapy against visceral leishmaniasis.

Selective anti-ErbB3 aptamer modified sorafenib microparticles: In vitro and in vivo toxicity assessment.

The delivery of aptamer modified therapeutic moieties to specific tissue sites has become one of the major therapeutic choices to reduce the toxicity of inhibitory drugs. Bearing this in mind, the current study was designed using sorafenib (SFB) encapsulated microparticles (MP) prepared with biodegradable poly (D, L-lactic-co-glycolic acid) (PLGA) copolymer. The surfaces of these microparticles were modified with RNA aptamer having a binding affinity towards ErbB3 receptors. SFB-loaded MP (MPS) were prepared by o/w solvent evaporation method and the surface was coupled with the amino group of aptamer by EDC/NHS chemistry. Physiochemical investigations were done by dynamic light scattering, scanning electron microscopy and FTIR. In vitro apoptosis assay, cell viability assay and metastatic progression showed a significant decrease (p < 0.001) in vitro cell viability for MPS and MPS-Apt as compared to MP. The synergistic combination of SFB and aptamer also decreased the metastatic progression of cells for an extended period. Microparticles were also evaluated for in vivo toxicity in female BALB/c mice. It was evident that the presence of aptamer decreased the generalized toxicity of MPS-Apt, as measured by mean body weight loss and blood profiles, keeping all the blood formed elements level within acceptable limits. The histopathological investigations showed some necrotic and pyknotic bodies. In a similar fashion, liver function test and renal function tests showed pronounced effects of formulations on vital organs.