Most of the newly developed drugs fails to achieve sufficient bioavailability in to brain due to low water solubility and low permeability. Drug delivery systems are one method for achieving entry of molecules to their desired site of action within the body. Dendrimers are the customizable nanopolymers with uniform and well-defined particle size and shape. Dendrimers are of eminent interest for biomedical applications because of their ability to cross cell membranes. This potential pharmaceutical delivery system crosses the blood brain barrier (BBB) and other important target points. The high level of control over the dendritic architecture (size, branching density, surface functionality) make dendrimers ideal carriers in the field of brain drug delivery of anticancer, antiinflammatory, and antimicrobial agents. Examples of dendrimers such as poly(amidoamine) (PAMAM), poly(propylene imine) (PPI) and polyether-copolyester (PEPE), Glyco, PEGylated, peptide and pH dendrimers are of outmost significance. These dendrimers carry the drug molecules by physical interactions (encapsulation) or through chemical bonding (prodrug approach), while pH sensitive dendrimers are able to deliver drug molecules by alteration of ionic exchange in the brain microenvironment at the tumor site. Techniques employing dendrimers could be especially useful for drugs targeting to Alzheimer's and Prion's diseases. The present review should be of value to scientists who wish to work on the dendrimers for the delivery of molecules into the brain by systemic dosing.
: At present, cancer is the most deadly disease and one of the most common causes of death worldwide providing different obstacles to chemotherapy including non-specific biodistribution of chemotherapeutic drugs, dose-related adverse effects, development of metastasis and chemoresistance. Nanoparticle-based targeted delivery of chemotherapeutics gained enormous attention in the treatment of solid tumors as they provide many significant advantages including prolonged drug release, enhanced systemic half-life, decreased toxicity and targeted drug delivery. Polymer–lipid hybrid nanoparticles (PLHNPs) are the most effective nanoplatform that develop from building blocks of polymers and lipids. PLHNPs combine the unique advantages of both lipid-based nanoparticles as well as polymeric nanoparticles. PLHNPs integrate biocompatible polymers and biomimetic lipids in their architecture, which imparts PLHNPs with wide versatility for delivering chemotherapeutic drugs of different physicochemical characteristics to their target site of action. The hybrid architecture of PLHNPs provides many exceptional advantages such as small particle size, encapsulation of more than one anticancer drugs, high drug loading capacity and modified drug release profile. Furthermore, the surface decoration of PLHNPs improves the therapeutic potential of the chemotherapeutic drug by selective targeting of tumor tissue and reduces the side effects by decreasing non-specific biodistribution. This review highlights the challenges in the treatment of solid tumors by using nanoparticles system, rationale and targeting strategies of PLHNPs in the targeted treatment of solid tumors, and current progress of PLHNPs in the management of different types of solid tumors.
This project was designed to extract anti-hyperlipidaemic activity of simvastatin for the longer duration of time and the solubility enhancement of this BCS class II drug was also sought by preparing nanostructured lipid carrier (NLC). The method for NLC preparation involved melt-emulsification followed by ultrasonication. The developed formulation was optimized by 3-level, 3-factor Box-Behnken design. The independent variables were % lipid mixture, % surfactant and sonication time (minutes). The responses selected were particle size, PDI and entrapment efficiency. The optimized formulation had particle size 114.62 ± 5.65, PDI 0.210 ± 0.034 and entrapment efficiency 85.20 ± 7.98%. The optimized formulation was further characterized by TEM and SEM. Spherical shape and nano size distribution of the optimized formulation were confirmed by SEM and TEM, respectively. The DSC of optimized formulation hints for the loss of crystalline nature of drug whereas the FT-IR spectra reveal that there is no interaction between drug and excipients when incorporated in NLC. The drug release from the NLC was biphasic (burst release was followed by sustained release). The kinetic of drug release followed Fickian diffusion with Korsmeyer-Peppas model. When the antihyperlipidaemic activity of SMV-NLC was compared with SMVsuspension, it was found that SMV-NLC significantly decreased the total cholesterol and triglyceride level by 2.77 and threefolds, respectively.
The aim of this investigation was to develop and analyze a tacrolimus and thymoquinone co-loaded nanostructured lipid carriers (TAC-THQ-NLCs)-based nanogel as a new combinatorial approach for the treatment of psoriasis. The NLCs were formulated by an emulsification-solvent-evaporation technique using glyceryl monostearate, Capryol 90 (oil), and a mixture of Tween 80 and Span 20 as a solid lipid, liquid lipid, and surfactant, respectively. Their combination was optimized using a three-factor and three-level Box–Behnken design (33-BBD). The optimized TAC-THQ-NLCs were observed to be smooth and spherical with a particle size of 144.95 ± 2.80 nm, a polydispersity index of 0.160 ± 0.021, a zeta potential of ‒29.47 ± 1.9 mV, and an entrapment efficiency of > 70% for both drugs. DSC and PXRD studies demonstrated the amorphous state of TAC and THQ in the lipid matrix of the NLCs. An FTIR analysis demonstrated the excellent compatibility of the drugs with the excipients without interactions. The TAC-THQ-NLC-based nanogel (abbreviated as TAC-THQ-NG) exhibited a good texture profile and good spreadability. The in vitro release study demonstrated a sustained drug release for 24 h from the TAC-THQ-NG that followed the Korsmeyer–Peppas kinetic model with a Fickian diffusion mechanism. Moreover, the TAC-THQ-NG revealed significantly higher dose-dependent toxicity against an HaCaT cell line compared to a TAC-THQ suspension gel (abbreviated as TAC-THQ-SG). Furthermore, the developed formulations demonstrated antioxidant activity comparable to free THQ. Confocal microscopy revealed improved permeation depth of the dye-loaded nanogel in the skin compared to the suspension gel. Based on these findings, it was concluded that TAC-THQ-NG is a promising combinatorial treatment approach for psoriasis.
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