Self assembly of small molecules in complex supramolecular structures provides a new avenue in the development of materials for drug delivery applications. Owing to the low aqueous solubility of various drugs, an effective delivery system is often required to reach sufficient drug bioavailability and/or to facilitate clinical use. Micelles, amphiphilic gels, vesicles (liposomes), nanodisks, cubosomes, colloidosomes, tubules, microemulsions, lipid particles, polyelectrolyte capsules etc. are some of the intriguing structures formed via self assembly. As well as enabling improved solubilization, such materials can be tuned to offer a range of other advantages, including controlled or stimuli sensitive drug release, protection from drug hydrolysis and chemical or enzymatic degradation, a reduction in toxicity, improvement of drug availability, prevention of RES uptake or selective targeting to organelles etc. Such multiple functionalities can be brought together by self assembly of different functional molecules. This route offers a cost effective means of developing drug delivery carriers tailored to specific needs. Our current understanding of the microstructure evolution of self assembled materials will go a long way towards designing/selecting molecules to create well defined structures. We believe that most of the potential resources mentioned above are untapped and that there is a need to further strengthen research in this area to fully exploit their potential. Selective cross linking of core or shell, stimuli sensitive amphiphiles, prodrug amphiphiles, antibody coupled amphiphiles etc. are only some of the new approaches for the development of effective drug delivery systems via self assembly.

Self assembled materials: design strategies and drug delivery perspectives

The objective of the present investigation was to evaluate ability of the novel self-assembled phospholipid- based cationic nanocarriers (LeciPlex) in improving the therapeutic efficacy of a poorly water-soluble natural polyphenolic agent, quercetin (QR), on oral administration. Quercetin loaded LeciPlex (QR-LeciPlex) were successfully fabricated using a biocompatible solvent Transcutol HP. The QR-LeciPlex were characterized for particle size, encapsulation efficiency, zeta potential, and particle morphology by cryo-TEM. UV and fluorescence spectral characterization was carried out to find out the association of QR with LeciPlex. Small angle neutron scattering studies (SANS) were carried out to understand the internal structure of Leciplex and to evaluate the influence of the incorporation of QR in the LeciPlex. Anti-inflammatory and antitumorigenic activity of QR-LeciPlex was determined in comparison to QR suspension to evaluate the potential of LeciPlex in improving oral delivery of QR. QR-LeciPlex exhibited a particle size of ∼400 nm and had excellent colloidal stability. The QR-LeciPlex had a zeta potential greater than +30 mV and exhibited very high encapsulation efficiency of QR (>90%). UV and fluorescence spectral characterization indicated the interaction/association of QR with LeciPlex components. Cryo-TEM studies showed that LeciPlex and QR-LeciPlex have a unilamellar structure. SANS confirmed the unilamellar structure of LeciPlex and indicated that the incorporation of QR does not have any effect on the internal structure of the LeciPlex. QR-LeciPlex exhibited significantly higher anti-inflammatory and antitumorigenic activity (p < 0.01) as compared to that of QR suspension on oral administration.

Lecithin-based novel cationic nanocarriers (Leciplex) II: improving therapeutic efficacy of quercetin on oral administration.

Lecithin-based novel cationic nanocarriers (LeciPlex) I: fabrication, characterization and evaluation.

The shear-induced transformations between oriented planar lamellae and a state of closely packed multilamellar vesicles (MLVs) in a lyotropic nonionic surfactant model system were studied by the combination of nuclear magnetic resonance (NMR) spectroscopy and diffusometry with magnetic resonance imaging (MRI). 2H NMR imaging confirmed the discontinuous nature of the transition from onions to planar lamellae, revealing the spatial coexistence of both states within the gap of the cylindrical Couette geometry. On the other hand, NMR diffusion measurements in three principal directions and at various values of strain strongly suggest that a multi-lamellar cylindrical or undulated intermediate structure exists during the continuous and spatially homogeneous transition from planar lamellae to MLVs

/pdf/planar-lamellae-and-onions-a-spatially-resolved-rheo-nmr-2b8parr5gk.pdf

Planar lamellae and onions: a spatially resolved rheo–NMR approach to the shear-induced structural transformations in a surfactant model system

Different dimensions of commercially available microneedle devices, namely, Admin- Patch(®) microneedle arrays (MN) (0.6, 0.9, 1.2 and 1.5 mm lengths) and Dermaroller(®) microneedle rollers (DR) (0.5 and 1mm lengths) were evaluated for their relative efficiency in enhancement of transdermal permeation of Sumatriptan (SMT). Solubility assessment of SMT was carried out using propylene glycol (PG), polyethylene glycol (PEG) in combination with saline (S) at different ratios and the order of solubility was found to be 70:30 > 80:20 > 90:10 %v/v in both PG:S and PEG:S. In vitro skin permeation studies were performed using PG:S (70:30 %v/v) as donor vehicle. A significant increase in cumulative amount of SMT permeated, steady state flux, permeability coefficient and diffusion coefficient values were observed after microneedle treatment, and the values were in the order of 1.5mm MN >1.2mm MN >0.9mm MN >1mm DR >0.6mm MN >0.5mm DR > passive permeation. Lag times were significantly shorter after longer microneedle application (0.24h for 1.5mm MN). Arrays were found to be superior to rollers with similar microneedle lengths in enhancing SMT permeation and may be attributed to higher density of microneedles and force of application onto skin. The in vitro flux values revealed that 2.5cm(2) area patch is sufficient for effective therapy after treatment of skin with 1.5mm MN. It may be inferred that microneedle application significantly enhances the transdermal penetration of SMT and that it may be feasible to deliver clinically relevant therapeutic levels of SMT using microneedle assisted transdermal delivery systems.

In Vitro Skin Permeation Enhancement of Sumatriptan by Microneedle Application.

Onion Phases of PEG-8 Distearate

Oral rehydration salts (ORS) powder must be reconstituted accurately with water before consumption to avoid incorrect concentration (recommended osmolality: 245 mOsmol/kg). A consumer behavior study was conducted to understand the process of preparing ORS solution by respondents/caregivers; thereafter, the prepared solutions were tested for osmolarity. Respondents/caregivers ( n = 120) from Bengaluru and Pune, who were prescribed ORS from three different brands, either in small (4.2–4.4 g in 200 ml water) or large sachets (21–21.8 g in 1,000 ml water) in the past 3 weeks, were enrolled. The quantity of water and powder, type of water, size of the ORS sachet, and preparation method were recorded. Prepared ORS solutions were tested for osmolality using the United States Pharmacopeia method <785>. Recorded osmolality showed wide variability, ranging from 30 to 1,331 mOsmol/kg. The majority of prepared ORS solutions (52/120, 43%) were >310 mOsmol/kg; 35/120 (29.16%) were in the range of 200–310 mOsmol/kg, and only 17/120 (14.16%) were in the reduced osmolality range of 210–268 mOsmol/kg. The volume of water and quantity of powder used ranged between 100–1,000 ml and 1.38–23 g, respectively. Respondents/caregivers reconstituted the powdered ORS as per their own preferences, regardless of labeled instructions. Reconstitution variations led to a deviation in the resulting osmolality of the ORS solution from the recommended value of 245 mOsmol/kg. Respondents/caregivers should be counseled on the correct method of reconstituting ORS powder and the potential adverse effect of incorrect concentration of ORS, if not prepared as per the labeled instructions.

/pdf/wide-variability-in-osmolality-of-reconstituted-powdered-3oovj6ej.pdf

Wide variability in osmolality of reconstituted powdered oral rehydration salts due to disparity in the method of preparation among Indian consumers

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Onion Phases of PEG-8 Distearate

Wide variability in osmolality of reconstituted powdered oral rehydration salts due to disparity in the method of preparation among Indian consumers