This critique examines a 2019 investigation by Kochar and colleagues, which engineered a liposomal hydrogel

for the concurrent topical administration of Minoxidil (MXD) and Tretinoin (TRET) in addressing

evaluation. This review suggests specific remedial actions and prospective research avenues to address these

deficiencies, promoting dedicated in vivo trials, sophisticated analytical methods for interaction analysis, and a

more thorough stability-indicating protocol. The engineered system shows substantial promise, yet additional

verification is necessary to transform this encouraging ex vivo outcomes into a viable clinical treatment.

Androgenetic alopecia (AGA) is a prevalent hereditary condition characterized by the progressive

miniaturization of hair follicles, affecting a significant proportion of the global population (Otberg et al.,

2007). First-line topical treatment often involves Minoxidil (MXD), a vasodilator believed to prolong the

anagen phase and enhance cutaneous blood flow (Suchonwanit et al., 2019). Tretinoin (TRET), a retinoid

suboptimal formulations (Adil & Godwin, 2017). Advanced drug delivery systems, particularly nanocarriers

like liposomes, offer a promising solution. These phospholipid-based vesicles can encapsulate both hydrophilic

(MXD in the aqueous core) and lipophilic (TRET in the lipid bilayer) drugs, enhance follicular targeting,

provide a sustained-release depot within the skin, and reduce the irritancy of encapsulated agents (Mura et al.,

2007; Desai & Patlolla, 2019).

The study by Kochar et al. (2019) aimed to leverage these advantages by developing a co-loaded liposomal

system incorporated into a Carbopol hydrogel. This review provides a critical analysis of their methodology,

highlights the strengths of the formulated system, identifies major scientific and methodological gaps, and

offers targeted recommendations for future research to bridge the divide between promising formulation and

proven therapeutic agent.

Reboost hair-growth

The primary objective of Kochar et al. was to design, optimize, and characterize a stable liposomal hydrogel

for the simultaneous topical delivery of MXD and TRET. The rationale was based on the potential synergy

between the two drugs and the beneficial properties of liposomes (improved skin penetration, follicular

targeting, reduced irritation) combined with the advantages of a hydrogel base (ease of application, sustained

release, improved patient compliance).

the thin-film hydration technique followed by probe sonication for size reduction.

efficiency (%EE), and structure (TEM). All preparations exhibited nanoscale sizes (<200 nm), low PDI (<0.4),

and outstanding %EE (>99% for single-drug liposomes; 83.5% for MXD and 71.4% for TRET in MTL).

hydrogel was evaluated for flow properties (shear-thinning behavior), pH (~6.5), spreadability, and drug

content.

the hydrogel relative to liposomal suspension. Significantly, TRET displayed no permeation but considerable

signs of irritation in a preliminary animal model.

vivo efficacy data. While ex vivo permeation and follicular delivery are promising, they are surrogate markers.

Demonstrating actual hair growth promotion—through measures such as anagen-to-telogen ratio, hair count,

density, and follicle size in a validated animal model of AGA (e.g., testosterone-induced alopecia in mice or

C57BL/6 mice)—is imperative to claim therapeutic efficacy. Without this data, the clinical relevance of the

formulation remains speculative.

synergistic effect between MXD and TRET. However, the study design lacks a critical control group: a

indicating method (e.g., HPLC with detection of degradation products) under ICH-recommended storage

conditions (accelerated and long-term) is a major flaw that questions the formulation's shelf-life and real-world

viability (Blessy et al., 2014).

observations. The reduction in EE% for both drugs in the co-loaded system (compared to single-loaded) is not

mechanistically investigated (e.g., via FTIR to study drug-lipid interactions). Similarly, the reduction in TRET-

induced irritation is attributed to the hydrogel but not proven through objective measures of inflammation (e.g.,

quantification of cytokines like IL-1α or TNF-α in tissue).

safe for chronic use, as AGA treatment requires long-term, daily application. A longer-term repeated

A conventional MXD solution (standard control)

A liposomal hydrogel containing MXD alone (to isolate TRET's contribution)

Endpoints should include histopathological analysis of skin biopsies, photographic assessment, and manual

hair count.

liposomes to directly examine the hypothesis that TRET augments MXD's efficacy. Statistical comparison

between the MXD-alone and MXD+TRET groups is imperative to substantiate synergy.

conducted. The formulation should be stored under accelerated (40°C ± 2°C / 75% RH ± 5% RH) and long-

term (25°C ± 2°C / 60% RH ± 5% RH) conditions for at least 6 months. Stability must be assessed using a

validated, stability-indicating HPLC method to track the degradation of both MXD and TRET.

preservatives for a multi-dose topical product.

The investigation by scientist denotes a substantial and praiseworthy advancement in the sophisticated topical

delivery of anti-alopecia drugs. The methodical development of a co-loaded liposomal hydrogel is

scientifically rigorous, and the findings concerning characterization, ex vivo permeation, follicular targeting,

and preliminary safety are highly encouraging. The formulation effectively tackles several main challenges of

conventional treatments.

Nonetheless, the lack of in vivo efficacy data and a direct comparison to confirm synergistic action are vital

flaws that leave the core therapeutic assertion unconfirmed. The transition from a well-defined formulation to

an established therapeutic agent necessitates closing this divide. By enacting the proposed solutions—